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Clinical performance of resin composite restorations: the value of accelerated in-vitro testing
Garcia-Godoy, F.
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Citation for published version (APA):Garcia-Godoy, F. (2012). Clinical performance of resin composite restorations: the value of accelerated in-vitrotesting.
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Download date: 08 Nov 2020
CClliinniiccaall ppeerrffoorrmmaannccee ooff rreessiinn ccoommppoossiittee rreessttoorraattiioonnss
The predictive value of accelerated in vitro testing
Franklin García-Godoy
Clinical perform
ance of resin com
posite restorations
F. G
arcía-Godoy
2012
UUiittnnooddiiggiinngg
Voor het bijwonen van de
openbare verdediging van
het proefschrift
Clinical performance of resin composite
restorations The predictive value of
accelerated in vitro testing
Op dinsdag 5 juni 2012 om
12:00 uur in de
Agnietenkapel
Ouderzijdsvoorburgwal 231
in Amsterdam
Na afloop van de promotie is
er een receptie ter plaatse
Franklin García-Godoy
Franklin Garcia-Godoy was born in 1952 in Santo Domingo, Dominican Republic. He graduated in Dentistry in the University of Santo Domingo in 1976 with the degree of Doctor of Odontology Cum Laude. He obtained a specialty degree in Pediatric Dentistry from the College of Dentistry, University of Illinois, in Chicago, USA in 1979 and also in 1979 a Master of Science degree from the Graduate College of the University of Illinois, in Chicago, USA. He has been a Professor with Tenure at the University of Texas Health Science Center at San Antonio, Texas, USA, Tufts University, Boston, USA and University of Tennessee, Memphis, Tennessee. He is also a Senior Clinical Investigator at the Forsyth Dental Research Center, in Cambridge, Massachusetts, USA and Adjunct Professor at the University of Munich, Germany. Currently, he is Senior Executive Associate Dean for Research, Chair, Department of Bioscience Research, and Director, Bioscience Research Center, College of Dentistry, University of Tennessee Health Science Center. He is also the Editor of the American Journal of Dentistry. He has published over 450 scientific articles. He began his PhD program in 2005 conducting the long-term clinical results presented in this thesis and is conducting research in areas ranging from sealants to stem cells.
Clinical performance of resin composite restorations:
The predictive value of accelerated in vitro testing
Franklin García-Godoy
Printed by: GVO drukkers en vormgevers B.V. | Ponsen & Looijen, Ede
Copyright: © F. Garcia-Godoy
All rights reserved. No part of this publication may be reproduced, stored in a retrieval
system, or transmitted in any form or by any means, mechanically, by photocopy, by
recording or otherwise, without permission by the author.
Clinical performance of resin composite restorations:
The value of accelerated in-vitro testing
ACADEMISCH PROEFSCHRIFT
Ter verkrijging van de graad van doctor
aan de Universiteit van Amsterdam
op gezag van de Rector Magnificus
Prof.dr. D.C. van den Boom
ten overstaan van een door het college voor promoties ingestelde
commissie, in het openbaar te verdedigen in de Agnietenkapel
op dinsdag 5 juni 2012, te 12:00 uur
door
Franklin Garcia-Godoy
Geboren 11 november 1952
te Santo Domingo, Dominicaanse Republiek
Promotiecommissie
Promotor : Prof. dr. A.J. Feilzer
Co-promotores : Prof.dr. R. Frankenberger
Prof.dr. N. Krämer
Overige leden : Prof.dr. R. Hickel
Dr. C.J. Kleverlaan
Prof.dr. J. McCabe
Prof.dr. F.J.M. Roeters
Faculteit der Tandheelkunde
Contents
Chapter 1 Introduction 7
Chapter 2 Degradation of resin-bonded human dentin after 3 years of
storage
17
Chapter 3 Long-term degradation of enamel and dentin bonds: 6-year
results in vitro vs. in vivo.
31
Chapter 4 Fatigue behavior of dental resin composites: Flexural fatigue in
vitro vs. six years in vivo
45
Chapter 5 Microhybrid vs. nanohybrid resin composites in extended
cavities after 6 years.
59
Chapter 6 General discussion: Is the clinical performance of bonded
restoratives predictable in the lab?
82
Summary 106
Samenvatting 112
Acknowledgement 118
7
CHAPTER 1
Introduction
Chapter 1
8
Tooth-colored materials such as resin-based composites are today the treatment option
of choice for the majority of patients.1-6 This is mainly attributed to esthetic reasons
and not primarily related to lifetime-expectancy of individual restorative approaches.
Amalgam was a successful dental restorative material for over 200 years.7-9 However,
on one hand it was repeatedly alleged to be toxic,10-12 and on the other hand it is dark
or at best argentic and therefore simply not invisible nor tooth-colored.13 Today we
also know that amalgam, among all toxicologic issues, also has clinical disadvantages:
missing adhesive stabilization of remaining tooth hard tissues, cracked teeth after long
service times, and mandatory cement linings are not desirable in today's restorative
therapy of carious lesions.13 Resin composites are invisible, adhesively stabilizing to
both enamel and dentin, and appropriately sealing.1-4;14-16 Nevertheless, is the distinct
change towards resin composites really better in terms of overall clinical
performance? What are resin composite restorations able to perform, especially
compared to amalgam in larger stress-bearing posterior cavities? Today it is well-
proven that adhesive restorations are successful, having been repeatedly reported for
pit and fissure sealings, direct and indirect resin composites, and bonded indirect
ceramic restorations.1;2;4;13;15;17-22 In the focus of the present thesis only directly
applied resin composite restorations were investigated, especially as posterior
rsestorations for amalgam replacement.
It is well-known from several studies in the field of adhesive dentistry that durable
adhesion to enamel and dentin is a fundamental prerequisite for successful adhesive
dentistry because polymerization shrinkage of resin-based composites is still a major
issue.2;3;5;6;23-27 Bonding to phosphoric acid etched enamel is generally accepted as
clinically successful.13;15;17;28;29 The same is true for dentin, however, it is not
completely understood whether the etch-and-rinse or the self-etch approach may
represent the ultimate way of durable bonding to dentin.14;15;18;23;24;26;28;30-32 And
technique sensitivity with bonded restorations still is problematic facing a 1:12 failure
rate ratio in a clinical trial with identical materials but different clinical operators.33
Beside technique sensitivity, long-term performance of adhesion to enamel and dentin
is one of the most interesting issues.1;6;13;14;18;19;21;22;30-32;34 In the literature, many short
term evaluations are published, but medium to long-term investigations are still
needed. Therefore, bonding degradation over time is an important aspect. In dentin,
the last decade revealed an array of innovative findings with regards to bond
Introduction
9
degradation, especially in dentin.14;35-38 Both water treeing and enzymatic degradation
investigations clearly showed that there is a long way to go for durable dentin bonding
also in the nanoscale aspect.14;30;31;36-38 Results up to three years are presented here,
giving some more aspects of longevity in vitro (Chapter 2).
Moreover, adhesion to enamel is even more important because the main retention is
provided by appropriate bonding to enamel margins, and the absence of marginal
staining is primarily provided by a tight enamel seal.4;17-19;28;32;39 When cavities get
larger and larger, dentin support of the biomechanical tooth-restoration complex gets
lost and restoration margins in enamel receive even more stress besides residual
shrinkage stress and intraoral chewing forces.19;20;23-27 Therefore, long-term
evaluations over six years also were carried out (Chapter 3). In this chapter, in vitro
results were not thought to stand alone. When the setups for a clinical study were
designed, it was an aim of the author to simultaneously start both in vivo and in vitro
studies; i.e. in vitro evaluations regarding marginal quality were started with the same
materials at the same time like the prospective randomized clinical trial dealing with
posterior resin composite restorations. So after several years of clinical service, one
should be able to directly compare in vitro results with in vivo outcomes.
Resin-dentin and resin-enamel bonding behavior is important for clinical success, but
resin composite research is not adhesion alone. Adhesion is certainly an important
issue as described above, but restorative material properties such as wear, flexural
strength, and flexural fatigue behavior are important as well.2;3;32;40-45 In former times
(being represented by older studies in the literature of the field), the predominant
failure mechanism of resin composite restorations was gap formation and subsequent
recurrent caries.34 Residual stresses led to gap formation over time, supported by
different coefficients of thermal expansion.1-3;32;34;40 Gaps are colonized by biofilms
consequently resulting in secondary caries. This scenario was believed to be the major
failure reason for decades and is still in the back of dentists’ minds all over the world.
However, facing more recent prospective clinical trials dealing with modern resin
composite materials for posterior use, it becomes evident that more material-
dependent issues like bulk fractures and chipping have displaced secondary caries as
the No 1 failure scenario with this class of materials.2;3;13;16;19;20;26;27;40;42;46-48 This may
be due to the better understanding of long-term bonding to both enamel and dentin,
Chapter 1
10
but it may also be attributed to enhanced materials properties in terms of shrinkage
and shrinkage stress.2;5;23;25;32
Randomized prospective clinical trials are still the ultimate instrument for evaluating
dental restoratives such as resin composites, ceramics, cements, and prosthodontic
restorations.4;15;16;46-49 However, the predominant problem with these clinical trials is
that once valuable results are available after several years of clinical service, the
material under investigation may not be in the market anymore. This is a frustrating
situation which often occurred with many research groups. Another problem is when
publishable results are obtained, the peer review periods and publication backlog of
top dental journals add considerable time and actual publication is postponed
significantly. Legislation in the field of medical products also contributes negatively
here; it becomes harder and harder to get ethical permission to carry out clinical trials,
costs for clinical centers have to be readjusted, and finally the manufacturer may not
have enough budget for the study anymore. Due to this considerable number of
reasons, preclinical in vitro investigations are more important than ever, but it is still
not fully understood whether these tests are able to reliably predict clinical behavior.
As already mentioned, the performance of bulky resin composites is of importance to
counteract bulk fractures over time.17;32;40-42;50;51 Therefore, a thorough in vitro vs. in
vivo comparison of flexural fatigue characteristics of resin composites must be
addressed here (Chapter 4). In this case, the strategy was the same as in bonding
investigations of Chapter 3. Again, we simultaneously started both in vitro and in vivo
branches of the overall investigation plan. However, compared to the informative
value of thermomechanical loading for marginal quality estimation, loading of resin
composite beams is controversially discussed. On one hand, any fatigue loading
design is superior to pure initial loading alone.17;32;40-42;50;51 Initially, high loading
forces seldomly lead to clinical failures in real life.13;20;43 It is more the subcritical,
repeated load that degrades dental restorations over several years of clinical service.
Loading of beams - with fatigue or not - may not be very close to the clinical
situation, because in the oral cavity no resin composite beam may be found to be
loaded. Intraorally, resin composites are always bonded more or less successfully to
dental hard tissues, i.e. bending forces such as those observed in a classical three- or
four-point flexural strength evaluation may not occur similarly.13;20;43 Nevertheless,
the practical advantage of the presented four-point flexural fatigue evaluation design
Introduction
11
is of a very thoroughly standardized quality and moreover, a sound database of many
restoratives exists for comparison.32;41;42 So we decided to include this particular way
of stressing resin composite specimens in order to simulate bulk fatigue over time.
And finally, again we were able to correlate the results to clinical outcome directly.
The ultimate instrument is still the randomized clinical trial. Therefore, a prospective
clinical long-term trial was set up and reported (Chapter 5). As mentioned above,
both materials under investigation are no longer on the market. . On the other hand, a
certain amount of valuable information results from the present long-term evaluation
of Grandio and Tetric Ceram. The longitudinal approach allows for the correlation of
initial cavity size with marginal degradation over time. It is possible to measure wear
in both areas, occlusal contact area and contact-free area, and distinct differences
among materials can be worked out. Chapter 5 is the heart and center of the present
thesis, because it allows a clear view on what is happening with adhesively bonded
resin composites in stress-bearing areas of posterior teeth.4;16;18;46-48 It is possible to
distinguish between smaller, minimally invasive resin composite restorations, and
larger restorations with considerable occlusal contacts in resin composite instead of
being underpinned by more wear resistant enamel cusps. Last but not least, a
prospective clinical long-term trial offers the possibility of getting hints about the
ultimate question of how resin composite restorations behave over time and what
failure scenarios are really in the center of interest. This is the clear advantage
compared to cross-sectional studies offering important observation, but unfortunately
in a clearly retrospective nature.25;34
The final question remains and should be addressed with the last issue of the present
thesis, i.e. what is this all about or in different words: Is clinical performance of
bonded restoratives predictable in the lab (Chapter 6)? It was extensively discussed
previously, and it has to be the final statement of the present thesis. The key idea for
valuably estimating this particular and ultimate question was to start with in vitro and
in vivo research simultaneously.17;29 Only in this way was it possible to truly compare
preclinical outcome and clinical observations. And only when evaluated parameters in
both branches approximately match, the predictive quality of the chosen in vitro setup
is appropriate. This is the simple truth regarding the major question of the present
thesis, before smart materials avoiding classical material disadvantages are considered
as alternative.52
Chapter 1
12
References 1. Da Rosa Rodolpho PA, Donassollo TA, Cenci MS et al. 22-Year clinical
evaluation of the performance of two posterior composites with different filler characteristics. Dent Mater 2011.
2. Ferracane JL. Buonocore Lecture. Placing dental composites--a stressful experience. Oper Dent 2008;33:247-257.
3. Ferracane JL. Resin composite--state of the art. Dent Mater 2011;27:29-38.
4. Hickel R, Manhart J. Longevity of restorations in posterior teeth and reasons for failure. J Adhes Dent 2001;3:45-64.
5. Mjor IA. Esthetic dentistry--the future. J Esthet Dent 2000;12:281-283.
6. Mjor IA. Minimum requirements for new dental materials. J Oral Rehabil 2007;34:907-912.
7. Maserejian NN, Trachtenberg F, Hayes C, Tavares M. Oral health disparities in children of immigrants: dental caries experience at enrollment and during follow-up in the New England Children's Amalgam Trial. J Public Health Dent 2008;68:14-21.
8. Richardson GM, Wilson R, Allard D, Purtill C, Douma S, Graviere J. Mercury exposure and risks from dental amalgam in the US population, post-2000. Sci Total Environ 2011.
9. Trachtenberg F, Maserejian NN, Tavares M, Soncini JA, Hayes C. Extent of tooth decay in the mouth and increased need for replacement of dental restorations: the New England Children's Amalgam Trial. Pediatr Dent 2008;30:388-392.
10. Mutter J, Naumann J, Sadaghiani C, Walach H, Drasch G. Amalgam studies: disregarding basic principles of mercury toxicity. Int J Hyg Environ Health 2004;207:391-397.
11. Mutter J, Naumann J. Blood mercury levels and neurobehavior. JAMA 2005;294:679-680.
12. Mutter J. Is dental amalgam safe for humans? The opinion of the scientific committee of the European Commission. J Occup Med Toxicol 2011;6:2.
13. Manhart J, Chen H, Hamm G, Hickel R. Buonocore Memorial Lecture. Review of the clinical survival of direct and indirect restorations in posterior teeth of the permanent dentition. Oper Dent 2004;29:481-508.
14. Carvalho RM, Chersoni S, Frankenberger R, Pashley DH, Prati C, Tay FR. A challenge to the conventional wisdom that simultaneous etching and resin
Introduction
13
infiltration always occurs in self-etch adhesives. Biomaterials 2005;26:1035-1042.
15. Hickel R, Manhart J, Garcia-Godoy F. Clinical results and new developments of direct posterior restorations. Am J Dent 2000;13:41D-54D.
16. Hickel R, Peschke A, Tyas M et al. FDI World Dental Federation - clinical criteria for the evaluation of direct and indirect restorations. Update and clinical examples. J Adhes Dent 2010;12:259-272.
17. Frankenberger R, Garcia-Godoy F, Lohbauer U, Petschelt A, Krämer N. Evaluation of resin composite materials. Part I: in vitro investigations. Am J Dent 2005;18:23-27.
18. Gordan VV, Shen C, Watson RE, Mjor IA. Four-year clinical evaluation of a self-etching primer and resin-based restorative material. Am J Dent 2005;18:45-49.
19. Krämer N, Garcia-Godoy F, Reinelt C, Frankenberger R. Clinical performance of posterior compomer restorations over 4 years. Am J Dent 2006;19:61-66.
20. Krämer N, Reinelt C, Richter G, Petschelt A, Frankenberger R. Nanohybrid vs. fine hybrid composite in Class II cavities: clinical results and margin analysis after four years. Dent Mater 2009;25:750-759.
21. Manhart J, Chen HY, Mehl A, Hickel R. Clinical study of indirect composite resin inlays in posterior stress-bearing preparations placed by dental students: results after 6 months and 1, 2, and 3 years. Quintessence Int 2010;41:399-410.
22. Manhart J, Chen HY, Hickel R. Clinical evaluation of the posterior composite Quixfil in class I and II cavities: 4-year follow-up of a randomized controlled trial. J Adhes Dent 2010;12:237-243.
23. Opdam NJ, Loomans BA, Roeters FJ, Bronkhorst EM. Five-year clinical performance of posterior resin composite restorations placed by dental students. J Dent 2004;32:379-383.
24. Opdam NJ, Bronkhorst EM, Roeters JM, Loomans BA. Longevity and reasons for failure of sandwich and total-etch posterior composite resin restorations. J Adhes Dent 2007;9:469-475.
25. Opdam NJ, Bronkhorst EM, Roeters JM, Loomans BA. A retrospective clinical study on longevity of posterior composite and amalgam restorations. Dent Mater 2007;23:2-8.
26. Opdam NJ, Bronkhorst EM, Loomans BA, Huysmans MC. 12-year survival of composite vs. amalgam restorations. J Dent Res 2010;89:1063-1067.
Chapter 1
14
27. Opdam NJ, Bronkhorst EM, Cenci MS, Huysmans MC, Wilson NH. Age of failed restorations: A deceptive longevity parameter. J Dent 2011;39:225-230.
28. Frankenberger R, Tay FR. Self-etch vs etch-and-rinse adhesives: effect of thermo-mechanical fatigue loading on marginal quality of bonded resin composite restorations. Dent Mater 2005;21:397-412.
29. Frankenberger R, Krämer N, Lohbauer U, Nikolaenko SA, Reich SM. Marginal integrity: is the clinical performance of bonded restorations predictable in vitro? J Adhes Dent 2007;9 Suppl 1:107-116.
30. Breschi L, Cammelli F, Visintini E et al. Influence of chlorhexidine concentration on the durability of etch-and-rinse dentin bonds: a 12-month in vitro study. J Adhes Dent 2009;11:191-198.
31. Breschi L, Mazzoni A, Nato F et al. Chlorhexidine stabilizes the adhesive interface: a 2-year in vitro study. Dent Mater 2010;26:320-325.
32. Ilie N, Hickel R. Resin composite restorative materials. Aust Dent J 2011;56 Suppl 1:59-66.
33. Frankenberger R, Reinelt C, Petschelt A, Krämer N. Operator vs. material influence on clinical outcome of bonded ceramic inlays. Dent Mater 2009;25:960-968.
34. Mjor IA, Moorhead JE, Dahl JE. Reasons for replacement of restorations in permanent teeth in general dental practice. Int Dent J 2000;50:361-366.
35. Kim YK, Mai S, Mazzoni A et al. Biomimetic remineralization as a progressive dehydration mechanism of collagen matrices--implications in the aging of resin-dentin bonds. Acta Biomater 2010;6:3729-3739.
36. Sadek FT, Braga RR, Muench A, Liu Y, Pashley DH, Tay FR. Ethanol wet-bonding challenges current anti-degradation strategy. J Dent Res 2010;89:1499-1504.
37. Sadek FT, Castellan CS, Braga RR et al. One-year stability of resin-dentin bonds created with a hydrophobic ethanol-wet bonding technique. Dent Mater 2010;26:380-386.
38. Tay FR, Frankenberger R, Krejci I et al. Single-bottle adhesives behave as permeable membranes after polymerization. I. In vivo evidence. J Dent 2004;32:611-621.
39. Frankenberger R, Pashley DH, Reich SM, Lohbauer U, Petschelt A, Tay FR. Characterisation of resin-dentine interfaces by compressive cyclic loading. Biomaterials 2005;26:2043-2052.
Introduction
15
40. Ilie N, Hickel R. Investigations on mechanical behaviour of dental composites. Clin Oral Investig 2009;13:427-438.
41. Ilie N, Hickel R, Valceanu AS, Huth KC. Fracture toughness of dental restorative materials. Clin Oral Investig 2012, in press.
42. Keulemans F, Palav P, Aboushelib MM, Van DA, Kleverlaan CJ, Feilzer AJ. Fracture strength and fatigue resistance of dental resin-based composites. Dent Mater 2009;25:1433-1441.
43. Mjor IA. In vivo versus in vitro. J Am Dent Assoc 2004;135:1370, 1372.
44. Mjor IA. A recurring problem: research in restorative dentistry... But there is a light at the end of the tunnel. J Dent Res 2004;83:92.
45. Roeters FJ, de Jong LC, Opdam NJ. [Change to a new composite with low shrinkage not sensible at this point]. Ned Tijdschr Tandheelkd 2009;116:10-15.
46. Hickel R, Roulet JF, Bayne S et al. Recommendations for conducting controlled clinical studies of dental restorative materials. J Adhes Dent 2007;9 Suppl 1:121-147.
47. Hickel R, Roulet JF, Bayne S et al. Recommendations for conducting controlled clinical studies of dental restorative materials. Int Dent J 2007;57:300-302.
48. Hickel R, Roulet JF, Bayne S et al. Recommendations for conducting controlled clinical studies of dental restorative materials. Clin Oral Investig 2007;11:5-33.
49. Wilson NH, Gordan VV, Brunton PA, Wilson MA, Crisp RJ, Mjor IA. Two-centre evaluation of a resin composite/ self-etching restorative system: three-year findings. J Adhes Dent 2006;8:47-51.
50. Palaniappan S, Bharadwaj D, Mattar DL, Peumans M, Van MB, Lambrechts P. Nanofilled and microhybrid composite restorations: Five-year clinical wear performances. Dent Mater 2011;27:692-700.
51. Palaniappan S, Elsen L, Lijnen I, Peumans M, Van MB, Lambrechts P. Nanohybrid and microfilled hybrid versus conventional hybrid composite restorations: 5-year clinical wear performance. Clin Oral Investig 2012;16:181-190.
53. McCabe JF, Yan Z, Al Naimi OT, Mahmoud G, Rolland SL. Smart materials in dentistry. Aust Dent J 2011;56: Suppl. 1, 3-10.
Chapter 1
16
17
CHAPTER 2
Degradation of resin-bonded human dentin after 3 years of storage
Chapter 2
18
Introduction
Considerable evidence in adhesive dentistry has accumulated over the past decade,
based on in vitro and in vivo work. Dentin bonds created by resin-based adhesives
may not be as durable as previously conjectured.1 Although the current strategies of
incorporating ionic and hydrophilic resinous components in etch-and-rinse and self-
etch adhesives arise from the need to bond to an intrinsically wet substrate,2 they
create potentially unstable resin matrices that slowly degrade via water sorption.3 This
is particularly so when resin-dentin bonds are not protected by enamel, and when the
durability of these bonds was challenged by reducing adhesive interfaces into smaller
portions, to expedite aging effects and increasing their interactions with water.4-6
Another mechanism of bond degradation is the potential instability of the
demineralized dentin collagen matrix, that was manifested as the thinning or
disappearance of collagen fibrils from aged, bonded dentin,7,8 or the failure of aged
hybrid layers to take up heavy metal stains.4 This issue of collagen instability has
caused concern, with the demonstration of the potential involvement of host-derived
matrix metalloproteinases (MMPs), a class of independent endopeptidases, in the
breakdown of the collagen matrices in dentin caries9-11 and the periodontium.12-14 In
the context of dentin bonding, residual collagenolytic activity was observed in
mineralized dentin of extracted teeth that accounted for the disintegration of collagen
fibrils from unbonded, aged acid-etched dentin, in the absence of the contribution
from bacterial or salivary MMPs. This low but persistent endogenous collagenolytic
activity was strongly inhibited by the use of protease inhibitors, the incorporation of
which preserved the structural integrity of the collagen fibrils.1 In that study, the
demineralized collagen matrices were not protected by adhesives. Thus, it remains to
be resolved whether these endogenous enzymatic activities can result in the
proteolysis of the resin-infiltrated collagen network in aged, adhesive-bonded dentin.
Using a model that consisted of soluble fluorescein-labeled Type I collagen and
gelatin in a previous study, both collagenolytic and gelatinolytic activities were
identified in powdered mineralized human dentin. Retention of these activities was
evident even upon autoclaving of the mineralized dentin power in water. Conversely,
these activities were sufficiently suppressed after treatment of the powder with
phosphoric acid. The results derived from this model suggested that if resin-bonded
dentin is permeable to endogenous enzymes released from the underlying mineralized
dentin, complete cleavage of the collagen fibrils within the hybrid layer is possible,
Degradation of resin-bonded human dentin after 3 years of storage
19
first into ¾- and ¼-length fragments,15 and subsequently into smaller peptides.16 Thus,
the objective of the present study was to investigate the morphologic correlations of
these endogenous enzymatic activities in aged, adhesive-bonded dentin. As water
molecules are putatively required for the activity of zinc-dependent MMPs,17,18 the
null hypothesis tested was that there was no difference in the ultrastructure of resin-
dentin bonds that were aged in mineral oil or artificial saliva.
Materials and Methods
Twenty-one non-carious human third molars were collected after the subject’s
informed consent had been obtained under a protocol reviewed and approved by the
Human Assurance Committee of the Medical College of Georgia, USA. Within 1
month of extraction, the occlusal enamel and roots of these teeth were removed using
a slow-speed saw (Isometa) under water-cooling. The exposed dentin surfaces were
polished with wet 180-grit silicon carbide papers.
Experimenlal design - Three total-etch adhesives were examined. They included two
two-step systems (Prime&Bond NTb and Excitec), and a multi-step system (All-Bond
2d). Six teeth were used for each adhesive. Each tooth was etched with 32-37%
phosphoric acid gel for 15 seconds, and rinsed with water for 20 seconds. The teeth
were then bonded with the respective adhesives according to the manufacturers’
instructions, and restored with a microfilled resin composite (EPIC-TMPTe). After
allowing the bonds to mature for 24 hours, each tooth was sectioned longitudinally
into 0.9 mm-thick serial slabs. Two slabs from the center part of each tooth were
further sectioned into 0.9 x 0.9 mm beams. The composite-dentin beams from each
adhesive group were randomly divided into two equal portions and stored respectively
in 5 ml aliquots of artificial saliva or mineral oil at 55°C for 3 years, according to the
accelerated aging protocol described by Tay et al.19 The artificial saliva contained
(mmoles/L): CaCI2 (0.7), MgCl2 • 6H20 (0.2), KH2P04 (4.0), KCI (30), NaN3 (0.3) and
HEPES buffer (20). The rationale for using artificial saliva was to prevent
demineralization of the mineralized dentin during aging. The artificial saliva was
replaced every month during the 3-year period. Sodium azide was added to prevent
bacterial growth, and to ensure that the only available source of MMPs was derived
from the dentin substrate.1 The resin-bonded dentin beams that were to be aged in
mineral oil (Dow-Coming 200 Fluidf), were wiped with lint-free gauze and briefly air-
dried to remove excess water prior to immersion in oil. They served as controls in that
collagenolytic and gelatinolytic activity cannot occur in a non-aqueous medium.
Chapter 2
20
To further ensure that degenerative changes observed after accelerated aging were not
caused by the increased aging temperature (55°C), an "extreme" control was
performed for each adhesive, using an additional tooth that was bonded in the same
manner. Composite-dentin beams prepared from these teeth were subjected to an
autoclave cycle at 121°C and 103 kPa for 30 minutes in water before further
laboratory processing.
Transmission electron microscopy (TEM) - For each adhesive, 10 specimens were
randomly retrieved from those aged in mineral oil, and another 10 from the artificial
saliva at time zero and after 3 years of incubation. Half of the specimens were
immersed in a 50 wt% ammoniacal silver nitrate solution for 24 hours, according to
the tracer protocol for nanoleakage examination.2 These specimens were processed for
TEM examination without further laboratory demineralization. The remaining
specimens were completely demineralized in ethylene diamine tetra-acetic acid. Both
undemineralized and demineralized, epoxy resin-embedded, 90 µm-thick sections
were prepared according a TEM protocol.20 Undemineralized sections were examined
without further staining. Demineralized sections were stained with 2% uranyl acetate
and Reynold's lead citrate for examining the characteristics of the resin-dentin
interfaces, and with a specific collagen staining technique (1% phosphotungstic acid
and 2% uranyl acetate) for examination of the status of the collagen fibrils. The
sections were examined using a TEM (Philips EM208Sg) operating at 80 kV.
Results
The "extreme" control specimens that were autoclaved at 121°C showed that collagen
fibrils were not denatured at this temperature when they were protected by adhesive
resin or apatite minerals (not shown). Their ultrastructural features were similar to
those observed in control specimens that were aged in mineral oil at 55°C for 3 years.
For example, in undemineralized sections of Prime&Bond NT that were aged in
mineral oil, a 5-7 µm thick zone of demineralized dentin with sparse silver deposits
was observed (Fig. 2.1A), that corresponded with the electron-dense hybrid layer in
stained, demineralized sections (Fig. 2.1B). Collagen fibrils with normal dimensions
and organization could be identified both within the hybrid layer (Fig. 2.1C) and the
underlying dentin (Fig. 2.1D).
By contrast, extensive nanoleakage was observed in Prime&Bond NT specimens that
were aged in artificial saliva (Fig. 2.2A). The corresponding hybrid layer was
Degradation of resin-bonded human dentin after 3 years of storage
21
abnormal and only discontinuous patches of stained fibrillar remnants were observed
(Fig. 2.2B). They consisted of grossly disintegrated, short microfibrillar fragments
(Fig. 2.2C). The collagen matrix from the underlying mineralized dentin was also
denatured, but to a lesser extent, and appeared as swollen, partially unraveled fibrils
that lacked cross banding (Fig. 2.2D).
Whereas the Excite specimens that were aged in mineral oil exhibited minimal
nanoleakage (Fig. 2.3A) and a highly electrondense hybrid layer (Fig. 2.3B), those
that were aged in artificial saliva demonstrated substantial degenerative changes.
Extensive patches of nanoleakage could be seen in the zone of demineralized dentin
that extended into the underlying mineralized dentin (Fig. 2.3C). In such regions,
stained fibrillar components were absent from tbe hybrid layer. Collagen fibrils from
the underlying dentin were sparsely distributed among abnormally wide interfibrillar
spaces (Fig. 2.3D).
Stained fibrillar components were evident throughout the entire hybrid layer in All-
Bond 2 specimens that were aged in mineral oil (Fig. 2.4A). These banded collagen
fibrils exhibited the characteristic unraveling of their severed ends along the dentin
surface (Fig. 2.4B). In specimens that were aged in artificial saliva, crystalline
deposits (Fig. 2.4C) derived from the supersaturated artificial saliva (Pashley et al.1)
were seen along the adhesive-hybrid layer interface. Although nanoleakage was only
identified in discrete parts of the demineralized collagen matrix (Fig. 2.4C), the entire
hybrid layer was completely devoid of stained fibrillar components (Fig. 2.4D).
Chapter 2
22
Figure 2.1: Control resin-bonded dentin beams of Prime&Bond NT that were aged in mineral oil for 3 years. C: resin composite; A: adhesive; D: intertubular dentin. A. Unstained, undemineralized section of a specimen that has been immersed in ammoniacal silver nitrate. The electron-lucent zone of demineralized dentin (between open arrows) corresponded with the stained hybrid layer in Fig.2. lB. Areas of incomplete resin infiltration within this zone are represented by reticular patterns of silver deposits (nanoleakage; pointer). B. The corresponding image of the electron-dense hybrid layer (H) from a demineralized section that was stained with uranyl acetate and lead citrate. C. A demineralized section that was stained with phosphotungstic acid and uranyl acetate. Although the hybrid layer was electron-dense due LO the intense mordanting effect of the adhesive solution, cross banding could be identified in longitudinaHy-oriented collagen fibrils (arrow). D. Normal collagen dimensions and organization could
be identified from the laboratory demineralized, epoxy resin-infiltrated dentin beneath the hybrid layer.
Figure 2.2: Experimental resin-bonded beams of Prime&Bond NT that were aged in artificial saliva for 3 years. C: resin composite; A: adhesive; D: intertubular dentin. A. Unstained, undemineralized section after immersion in ammoniacal silver nitrate. Extensive silver impregnation (arrow) was present in the hybrid layer (between open arrows). The intertubular dentin appeared normal in the undemineralized section. B. Phosphotungstic acid and uranyl acetate stained, demineralized section showing the breaking down of collagen fibrils (pointer) within the hybrid layer (H). A substantial part of the hybrid layer was devoid of stainable fibrillar components. Oblique sections of resin tags (open arrowheads) could also be seen in the disintegrated hybrid layer. No bacteria was observed in the section. C. A high magnification view of the adhesive-hybrid layer interface, showing the stainable fibrillar remnants that were present within the hybrid layer (H). Collagenolysis resulted in the appearance of loose
strands of gelatin microfibrils (arrow). D. A high magnification view of the hybrid layer dentin junction where grossly disintegrated fibrillar remnants (pointer) were observed at the base of the hybrid layer (H). Further gelatinolysis by matrix metalloproteinases that diffused from the underlying dentin probably resulted in the breakdown of the gelatin strands into smaller peptides. This may account for the absence of stainable fibrillar components from the rest of the hybrid layer. Collagen fibrils in the laboratory demineralized dentin were denatured to a lesser extent, probably due to the protection rendered by the mineral phases. There was a loss of cross banding from these partially denatured and swollen fibrils, in which only the microfibrillar architctture could be identified (arrow).
Degradation of resin-bonded human dentin after 3 years of storage
23
Figure 2.3: Control (Figs. A, B) and experimental (Figs. C, D) resin-bonded dentin beams of Excite after 3 years of accelerated aging. C: resin composite; A: adhesive; D: intertubular dentin. A. Unstained, undemineralized section following immersion in ammoniacal silver nitrate. The control specimen that was aged in mineral oil exhibited relatively little silver uptake (pointer) within the demineralized dentin zone (between open arrows). B. The corresponding uranyl acetate and lead citrate-stained, demineralized section showing the presence of a highly electron dense hybrid layer (H) in which collagen fibrils could be clearly distinguished (arrow). C. Unstained, undemineralized section following immersion in ammoniacal silver nitrate. The experimental specimen that was aged in artificial saliva exhibited extensive areas of heavy silver deposits within the demineralized dentin zone (between open arrows) that extended into the underlying mineralized dentin (asterisk). The rest of the mineralized dentin appeared normal when
undeminera1ized sections were examined. D. The corresponding uranyl acetate and lead citrate-stained, demineralized section demineralized section showing a palely-stained hybrid layer (H) in which fibrillar components could not be identified. Stained collagen fibrils in the underlying intertubular dentin were sparse and separated by abnormally wide interfibrillar spaces (open arrow).
Figure 2.4: Control (Figs. A, B) and experimental (Figs. C, D) resin-bonded dentin beams of All-Bond 2 after 3 years of accelerated aging. C: resin composite; A: adhesive; D: intertubular dentin. A. Phosphotungstic acid and uranyl acetate stained, demineralized section of a control specimen that was aged in mineral oil, showing the presence of stained fibrillar components within the 5-6 µm thick hybrid layer (H and between open arrows). B. A high magnification view of the area depicted by the box in Fig.2. 4A. Collagen fibrils within the hybrid layer (H) were partially obscured by the infiltrated adhesive resins. Nevertheless, banded collagen fibrils could be identified (pointer), with unraveling of microfibrillar strands along the surface of the cut dentin (arrow). C. Unstained, undemineralized section of an experimental specimen that was aged in artificial saliva and examined after immersion in ammoniacal silver nitrate. Crystalline deposits (open arrowhead) derived from the supersaturated artificial saliva were
present between the adhesive and the surface of the cut dentin. The presence of segregated silver deposits within demineralized dentin zone (between open arrows) indicated that the latter was an intact layer, despite the absence of stainable fibrillar components (Fig 2..4D). D. The corresponding phosphotungstic acid and uranyl acetate-stained, demineralized section of a specimen that was aged in artificial saliva. The hybrid layer (H) was completely devoid of stainable fibrillar components, and exhibited a similar staining characteristic as the underlying resin tag (pointer) that is supposed to consist predominantly of adhesive resin. The activity of the phosphotungstic acid dissolved the crystalline deposits along the cut dentin surface (open arrowhead). At higher magnification (not shown), collagen fibrils within the underlying dentin were denatured and appeared as microfibrillar strands that were devoid of cross banding (Fig. 2.2D).
Chapter 2
24
Discussion
The null hypothesis had to be rejected as pronounced differences were present
between the mineral oil and artificial saliva specimens. The extent of nanoleakage,
interfacial staining characteristics, and the conditions of the collagen fibrils in both the
hybrid layers and the underlying dentin from all the adhesives were examined. As the
glass transition temperature of mineralized dentin is 166.7°C,21 it is not surprising that
the temperature of superheated steam (121°C) was insufficient to denature collagen in
mineralized or resin-infiltrated dentin. As the structural integrity of the collagen fibrils
were also preserved in all control specimens that were aged at 55°C in mineral oil, one
may confidently assert that the degenerative changes that occurred after accelerated
aging in artificial saliva was not caused by the increase in aging temperature. In the
absence of salivary and bacterial MMP activities, these changes must have been
initiated by the endogenous collagenolytic and gelatinolytic activities of the
mineralized dentin, confirming the results of our previous long-term study.1
The inability to take up heavy metal stains from water-aged hybrid layers has
previously been reported by DeMunck et al.4 The authors surmised that such a
phenomenon was due to the decline in polar groups along the surfaces of degrading
collagen fibrils. Using a specific collagen stain, we demonstrated the existence of
discontinuous patches of grossly disintegrated microfibrillar fragments in some of the
artificial saliva-aged interfaces (Fig. 2.2C). These fragments probably represented
remnant ¾- and ¼-length fragments that resulted from collagenolysis,22 but were
retained by the adhesive resins within the hybrid layer. The existence of mild to
moderate nanoleakage (i.e. silver uptake) in the hybrid layers that were aged in oil
suggested that these hybrid layers were initially permeable to water that was utilized
by residual MMP hydrolases to degrade the collagen matrix of the hybrid layer and
the underlying mineralized dentin. In resin-bonded specimens incubated in artificial
saliva for 3 years, the coexistence of areas that did and did not take up specific
collagen stains and areas exhibiting a complete lack of stainable fibrillar components
from other specimens (Figs. 2.3D, 2.4D) indicates that the degenerated microfibrillar
fragments have further been degraded beyond detection. Such a process may occur via
gelatinolytic MMPs released from the mineralized dentin, with the gelatin breaking
down into peptides of lower molecular weight (kDa). Such a phenomenon is
analogous to the appearance of clear bands in Coomassie bluestained gels, when the
cleavage products of gelatin were subjected to Western blotting after treatment with
MMP-2 (Gelatinase A) or MMP-9 (Gelatinase B).23,24
Degradation of resin-bonded human dentin after 3 years of storage
25
Although the collagenase MMP-8 has been shown to exist in carious human dentin,9
its endogenous origin has not been established. Conversely, the gelatinase MMP-2 has
been shown to be present in human dentin.25 Apart from its gelatinolytic activity via
fibronectin-like domains, MMP-2 is also capable of collagenolysis,26 albeit at a slower
rate, via its hemopexin domain.27 Thus, even in absence of an endogenous collagenase
source, endogenous MMP-2 from the dentin matrix can apparently result in the slow
but complete cleavage of the entire resin-infiltrated collagen network over 3 years.
Further immunolabeling of MMP-2 within freshly-prepared and aged dentin hybrid
layers should be performed to establish the role played by this proteolytic enzyme in
the degradation of the demineralized collagen matrix.
It is disturbing to observe consistent partial degradation of the underlying mineralized
dentin. Degradation was less severe than the hybrid layers, probably because the
collagen fibrils were better protected by apatites than by adhesive resins.
Nevertheless, this provides evidence that under specific circumstances, mineralized
dentin is capable of self-destruction by its own matrix-bound enzymes. Such a process
may require the activation of host-derived MMPs with acids, as purported in the
pathogenesis of dentin caries,l1 A provocative clinical concern is why self-degradation
and accompanying weakening of mineralized dentin has not been reported in teeth
bonded in vivo with dentin adhesives. A possible explanation is the disturbance of the
balance between MMPs and their natural inhibitors, TIMPs (tissue inhibitors of
metalloproteinases) when extracted teeth are used for aging experiments. It is known
that both TIMP-l and TIMP-2 can complex with active MMP-2 and inhibit proteolytic
activity.28,29 As these natural MMP inhibitors have shorter half-lives30 than MMPs,
prolonged interruption of MMP-TIMP interaction such as the cessation of dentin fluid
flow (i.e. in vitro conditions) may prevent the replenishment of pulpal TIMPs out into
peripheral dentin. While such ideas remain highly speculative, a similar degradation
of collagen fibrils has recently been shown in endodontically-treated teeth that have
undergone long-term clinical function.31 Clearly, more work is required to establish
the relationship between MMPs and their natural inhibitors, or the use of synthetic
inhibitors such as chlorhexidine or doxycycline, in prolonging the longevity of resin-
dentin bonds and or non-vital dentin in endodontically-treated teeth.
a. Buehler Ltd., Lake Bluff, IL, USA.
b. Dentsply DeTrey, Konstanz, Germany.
Chapter 2
26
c. Ivoclar-Vivadent, Schaan, Liechtenstein.
d. Bisco Inc., Schaumburg, IL, USA.
e. Parkell Inc., Edgewood, NY, USA.
f. Dow-Corning Corp., Midland, MI, USA.
g. Philips, Eindhoven, The Netherlands.
Degradation of resin-bonded human dentin after 3 years of storage
27
References
1. Pashley DH, Tay FR, Hashimoto M, Breschi L, Carvalho RM, Ito S.
Degradation of dentin collagen by host-derived enzymes during aging. J Dent
Res 2004;83:216-221.
2. Tay FR, Pashley DH. Have dentin adhesives become too hydrophilic? J Can
Dent Assoc 2003;69:726-731.
3. Yiu CK, King NM, Pashley DH, Suh BI, Carvalho RM, Carrilho MR, Tay FR.
Effect of resin hydrophilicity and water storage on resin strength. Biomaterials
2004;25:5789-5796.
4. DeMunck J, Van Meerbeek B, Yoshida Y, Inoue S, Vargas M, Suzuki K,
Lambrechts P, Vanherle G. Four-year water degradation of total-etch adhesives
bonded to dentin. J Dent Res 2003;82: 136-140.
5. Shono Y, Terashita M, Shimada J, Kozono Y, Carvalho RM, Russell CM,
Pashley DH. Durability of resin-dentin bonds. J Adhes Dent 1999;1: 211-218.
6. Hashimoto M, Ohno H, Sano H, Tay FR, Kaga M, Kudou Y, Oguchi H, Araki
Y, Kubota M. Micromorphological changes in resin-dentin bonds after 1 year
of water storage. J Biomed Mater Res 2002;63:306-311.
7. Hashimoto M, Ohno H, Sano H, Kaga M, Oguchi H. In vitro degradation of
resin-dentin bonds analyzed by microtensile bond test, scanning and
transmission electron microscopy. Biomaterials 2003;24:3795-3805.
8. Yoshida E, Hashimoto M, Hori M, Kaga M, Sano H, Oguchi H. Deproteinizing
effects on resin-tooth bond structures. J Biomed Mater Res Part B
2004;68B:29·35.
9. Tjaderhane L, Larjava H, Sorsa T, Uitto V-J, Larma M, Salo T. The activation
and function of host matrix metalloproteinases in dentin matrix breakdown in
carious dentin. J Dent Res 1998;77: 1622·1629.
Chapter 2
28
10. Sulkala M, Wahlgren I, Lannas M, Sorsa T, Teronen O, Salo T, Tjaderhane L
The effects of MMP inhibitors on human salivary MNIP activity and caries
progression in rats. J Dent Res 2001;80: 1545-1549.
11. van Strijp AJ, Jansen DC, DeGroot J, Ten Cate JM, Everts V. Host-derived
proteinases and degradation of dentine collagen in situ. Caries Res 2003;37:58-
65.
12. Kinane DF. Metalloproteinases in the pathogenesis of periodontal diseases.
Curr Opin Dent 1992;2:25-32.
13. Ryan ME, Ramamurthy S, Golub LM. Matrix metalloproteinases and their
inhibition in periodontal treatment. Curr Opin Periodontol 1996;3:85-96.
14. Gapski R, Barr JL, Sannent DP, Layher MG, Socransky SS, Giannobile WV.
Effect of systemic matrix metalloproteinase inhibition on perio-dontal wound
repair: A proof of concept trial. J Periodontol 2004;75:441-452.
15. Lauer-Fields JL, Iuska D, Fields GB. Matrix metalloproteinases and collagen
catabolism. Biopolymers 2002;66: 19-32.
16. Seltzer JL, Akers KT, Weingarten H, Grant GA, McCourt OW, Eisen AZ.
Cleavage specificity of human skin type IV collagenase (gelatinase).
Identification of cleavage sites in type I gelatin, with confirmation using
synthetic peptides. J Biol Chem 1990;265:20409-29413.
17. Overall CM. Molecular determinants of metalloproteinase substrate specificity:
Matrix metalloproteinase substrate binding domains, modules, and exosites.
Mol Biotechnol 2002;22:51-86.
18. Pelmenschikov V, Siegbahn PE. Catalytic mechanism of matrix metallo-
proteinases: Two-layered ONTOM study. Inorg Chem 2002;41:5659-5666.
19. Tay FR, Hashimoto M, Pashley DH, Peters MC, Lai SCN, Yiu CKY, Cheong
C. Aging affects two modes of nanoleakage expression in bonded dentin. J
Dent Res 2003;82:537-541.
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20. Tay FR, Moulding KM, Pashley DR. Distribution of nanofillers from a
simplified-step adhesive in acid conditioned dentin. J Adhes Dent 1999;1: 103-
117.
21. Annstrong SR, Jessop JL, Winn E, Tay FR, Pashley DH. Denaturation
temperatures of dentin matrices. I. Effect of demineralization and dehydration.
J Endod 2006; 32:638-641.
22. Gross J, Nagai Y. Specific degradation of the collagen molecule by tadpole
collagenolytic enzyme. Proc Natl Acad Sci USA 1965;54: 1197-1204.
23. Gendron R, Grenier D, Sorsa T, Mayrand D. Inhibition of the activities of
matrix metalloproteinases 2, 8, and 9 by chlorhexidine. Clin Diag Lab Immunol
1999;6:437-439.
24. Smith PC, Munoz VC, Collados L, Oyarzún AD. In situ detection of
matrixmetalloproteinase-9 (MMP-9) in gingival epithelium in human
periodontal disease. J Periodont Res 2004;39:87-92.
25. Martin-DeLas Heras S, Valenzula A, Overall CM. The matrix
metalloproteinase gelatinase A in human dentine. Arch Oral BioI 2000;45:757-
765.
26. Aimes RT, Quigley JP. Matrix metalloproteinase-2 is an interstitial
collagenase. Inhibitor-free enzyme catalyzes the cleavage of coHagen fibrils
and soluble native type I collagen generating the specific 3/4 and 1/4-length
fragments. J Biol Chem 1995;270:5872-5876.
27. Patterson ML, Atkinson SJ, Knauper V, Murphy G. Specific collagenolysis by
gelatinase A, MMP-2, is detennined by the hemopexin domain and not the
fibronectin-like domain. FEBS Lett 200 I ;503: 158-162.
28. Ward RV, Hembry RM, Reynolds JJ, Murphy G. The purification of tissue
inhibitor of metalloproteinases-2 from its 72 kDa progelatinase complex.
Demonstration of the biochemical similarities of tissue inhibitor of
Chapter 2
30
metalloproteinases-2 and tissue inhibitor of metalloproteinases-l. Biochem J
1991 ;278: 179-187.
29. Palosaari H, Pennington CJ, Lannas M, Edwards DR, Tjäderhane L, Salo T.
Expression profile of matrix. metalloproteinases (MMPs) and tissue inhibitors
of MMPs in mature human odontoblasts and pulp tissue. Eur J Oral Sci 2003;
111: 117-127.
30. Bode W, Fernandez-Catalan C, Grams F, Gomis-Ruth FX, Nagase H,
Tschesche H, Maskos K. Insights into MMP-TIMP interactions. Ann N Y Acad
Sci 1999;878:73-91.
31. Ferrari M, Mason PN, Goracci C, Pashley DH, Tay FR. Collagen degradation in endodontically treated teeth after clinical function. J Dent Res 2004;83:414-419.
31
CHAPTER 3
Long-term degradation of enamel and dentin bonds:
6-year results in vitro vs. in vivo.
Chapter 3
32
Introduction
Tooth-colored materials such as resin-based composites are today the treatment option
of choice for the majority of patients18,22,22,29, primarily due to esthetic demands. It is
well-proven that adhesive restorations are successful e.g. pit and fissure sealings,
direct and indirect resin composites, and bonded indirect ceramic
restorations.19,20,22,28,30,32,36 Durable adhesion to enamel and dentin still represents the
fundamental prerequisite due to polymerization shrinkage of resin-based
composites.2,8,9,21,23,24 Bonding to phosphoric acid etched enamel is widely accepted as
clinically viable,5,6,9,30,33-36 however, in dentin it is not completely clear whether the
etch-and-rinse or the self-etch approach may be more successful in getting durable
bonds.11,15,22,28,30,35 Irrespectively, technique sensitivity with bonded restorations
remains problematic facing a 1:12 failure rate ratio in clinical trials with identical
materials but different clinical operators.12,13
The primary goal of preclinical screening of dental materials should be to mimic the
clinical situation in order to predict clinical behavior. Therefore, researchers try to
predict clinical behavior of restoratives with laboratory in vitro investigations. Of
course, randomized clinical trials remain the ultimate instrument for evaluating dental
restoratives, however, a major problem with clinical trials is that when they give
valuable results after several years of clinical service, the material under investigation
may no longer be available in the market.3,4,24,27,31 Thus, preclinical in vitro
investigations are more important than ever, however, it is still not fully understood
whether these tests are able to reliably predict clinical behavior. So the aim of this
investigation was to compare preclinical results of a large marginal quality in vitro
database with clinically recorded marginal qualities of the same materials.
Materials and Methods
In vitro study: Thirty-two intact, non-carious, unrestored human third molars,
extracted for therapeutic reasons with patients’ approval, were stored in an aqueous
solution of 0.5% chloramine T at 4°C for up to 30 days. The teeth were debrided of
residual plaque and calculus, and examined to ensure that they were free of defects
under a light microscope at x20 magnification. Standardized class II cavity
preparation (MO, 4mm in width bucco-lingually, 2mm in depth at the bottom of the
proximal box) with proximal margins located 1-2 mm below the cementoenamel
Long-term degradation of enamel and dentin bonds: 6-year results in vitro vs. in vivo
33
junction were performed. The cavities were cut using coarse diamond burs under
profuse water cooling (80 µm diamond, Komet, Lemgo, Germany), and finished
with a 25 µm finishing diamond (one pair of diamonds per four cavities). Inner angles
of the cavities were rounded and the margins were not bevelled to deliver comparable
results to previous experiments.11,15
The prepared cavities (n=8) were treated with two different adhesives according to the
manufacturers’ instructions (n=16 with Syntac, Ivoclar Vivadent, Schaan, Principality
of Liechtenstein, and n=16 with Solobond M, Voco, Cuxhaven, Germany; Table 3.1).
The dentin adhesives and resin composite were polymerized with a Translux CL light-
curing unit (Elipar Trilight, 3M Espe, Seefeld, Germany). The intensity of the light
was checked periodically with a radiometer (Demetron Research Corp, Danbury, CT,
USA) to ensure that 600 mW/cm2 was always delivered during the experiments. The
adhesive was polymerized for 40 s prior to application of the resin composite in all
cases. The resin composites Tetric Ceram (Ivoclar Vivadent; shade A2) and Grandio
(Voco; shade A2) were used for all experimental restorations. Each cavity preparation
was bonded with the respective adhesive and restored incrementally with the resin
composite in layers up to 2 mm thickness. The increments were separately light-cured
for 40 s each with the light source in contact with the edge of the cavity. Prior to the
finishing process, visible overhangs were removed using a posterior scaler (A8 S204S,
Hu-Friedy, Leimen, Germany). Margins were finished with flexible disks (SofLex
Pop-on, 3M ESPE, St. Paul, USA).
After storage in distilled water at 37°C for 21 days, impressions (Provil Novo,
Heraeus Kulzer, Hanau, Germany) of the teeth were taken and a first set of epoxy
resin replicas (Alpha Die, Schuetz Dental, Rosbach, Germany) was made for SEM
evaluation. One pair of groups was subjected to storage in distilled water at 37°C for
2190 days.14 After storage, impressions were taken and thermo-mechanical loading of
specimens was performed in an artificial oral environment (“Quasimodo” chewing
simulator, University of Erlangen, Germany).
Chapter 3
34
In vitro specimens (n=32)
Syntac/Tetric Ceram (n=16) Solobond M/Grandio (n=16)
replicas after 21 days water storage
(baseline / n=16)
replicas after 21 days water storage
(baseline / n=16)
TML
100,000 x 50 N
2,500 x 5°C/55°C
WS
2190 days
TML
100,000 x 50 N
2,500 x 5°C/55°C
WS
2190 days
replicas (n=8) replicas (n=8) replicas (n=8) replicas (n=8)
TML
100,000 x 50 N
2,500 x 5°C/55°C
TML
100,000 x 50 N
2,500 x 5°C/55°C
replicas (n=8) replicas (n=8)
Table 3.1: Experimental setup in laboratory groups (TML: thermomechanical loading / WS: water storage).
Two specimens were arranged in one simulator chamber in proximal contact, similar
to the oral situation with the two restored marginal ridges in a normal intercuspation.15
The two adjacent lateral ridges were occluded against a steatite (a multi-component
semi-porous crystalline ceramic material) antagonist (6 mm in diameter) for 100,000
cycles at 50 N at a frequency of 0.5 Hz. The specimens were subjected to 2,500
thermal cycles between +5°C and +55°C by restoration the chambers with water in
each temperature for 30 s. The mechanical action and the water temperature within the
chewing chambers were checked periodically to ensure a reliable thermo-mechanical
loading (TML) effect. After completion of TML, a second set of replicas was
manufactured for later SEM analysis. The other pair of groups was subjected to TML
only.
In vivo study: In the course of a randomized clinical study with approval of a local
ethics committee, 30 subjects (23 female, 7 male, mean age 32.9 (24-59) years) with a
minimum of two restorations to be replaced in different quadrants received at least
two different Class II restorations (52 MO/OD, 16 MOD or more surfaces, no cusp
replacements) in a random decision.26 Thirty six Grandio restorations were bonded
with Solobond M (Voco) and 32 Tetric Ceram restorations were bonded with Syntac
Long-term degradation of enamel and dentin bonds: 6-year results in vitro vs. in vivo
35
(Ivoclar Vivadent). The cavities were cut using coarse diamond burs under profuse
water cooling (80 µm diamond, Komet, Lemgo, Germany), and finished with a 25 µm
finishing diamond. Inner angles of the cavities were rounded and the margins were not
bevelled. After cleaning and drying under rubber dam isolation (Coltene/Whaledent
Inc., Altstätten, Switzerland), adhesive procedures were performed with Solobond M
(2-step etch-and-rinse adhesive) and Syntac (4-step etch-and-rinse adhesive). The
resin composite materials were applied into the cavity in layers of approximately 2
mm thickness and adapted to the cavity walls with a plugger. Each layer was light
cured for 40 s (Elipar Trilight, 3M Espe, Seefeld, Germany). The occlusal region was
modeled as exactly as possible under intraoral conditions, avoiding visible overhangs.
The light-emission window was placed as close as possible to the cavity margins. The
intensity of the light was checked periodically with a radiometer (Demetron Research
Corp., Danburg, CT, USA) and was found to be consistently above 650 mW/cm2.
As soon as polymerization was completed, the surface of the restoration was
checked for defects and corrected when necessary. Visible overhangs were removed
with a scaler and the rubber dam was removed. Contacts in centric and eccentric
occlusion were checked with foils (Roeko, Langenau, Germany) and adjusted with
finishing diamonds (Komet Dental, Lemgo, Germany), shaped with flexible discs (3M
Dental, St. Paul, USA), super-fine discs (3M Dental, St. Paul, USA) and polishing
brushes (Hawe-Neos Dental, Bioggio, Switzerland). A fluoride varnish (Elmex Fluid,
GABA, Lörrach, Germany) was used to complete the treatment. Impressions were
used to make epoxy replicas (Alpha Die, Schütz Dental, Germany); 22 of them (n=11
per group) were subjected to scanning electron microscopic (SEM) analysis (Table
3.2). The replicas with the longest evaluable margins were selected randomly.
In vivo specimens (n=22)
Syntac/Tetric Ceram (n=11) Solobond M/Grandio (n=11)
replicas at initial recall (baseline / n=11) replicas at initial recall (baseline / n=11)
6 years of clinical function
replicas (n=11) replicas (n=11)
Table 3.2: Procedure for in vivo groups.
Chapter 3
36
All in vitro and in vivo replicas were mounted on aluminum stubs, sputter-coated with
gold and examined under a SEM (Leitz ISI 50, Akashi, Tokyo, Japan) at x200
magnification. SEM examination was performed by one operator having experience
with quantitative margin analysis who was blinded to the restorative procedures. The
marginal integrity between resin composite and enamel was expressed as a percentage
of the entire judgeable margin length. Marginal qualities were classified according to
the criteria “continuous/gap-free margin” and “gap/irregularity”, non-judgeable parts
and artifacts were excluded. Afterwards the percentage “gap-free margins” in relation
to the individual judgeable margins was calculated as marginal integrity. For in vivo
specimens, all non-judgeable parts such as overhangs were excluded with the
remaining criteria having been either “continuous margin” or “gap/irregularity”
(crevice, negative step formation, or marginal fracture in enamel or resin composite).
For better comparison with in vitro results, gap-free margins were added whether
there was a crevice or not. Marginal quality in dentin was not recordable with the
impression/replica technique. However, clinical criteria such as secondary caries were
evaluated.
Statistical analysis was performed using SPSS 14.0 (SPSS Inc., Chicago, IL, USA).
As the majority of groups in each of the two investigations did not exhibit normal data
distribution (Kolmogorov-Smirnov test), non-parametric tests were used (Wilcoxon
matched-pairs signed-ranks test, Mann-Whitney-U test) for pairwise comparisons at
the 95% significance level.
Results
An overview of the results is shown in Table 3.3. In both the in vitro and in vivo
scenario, marginal quality of resin composite restorations was significantly
deteriorated over time (p<0.05; Wilcoxon test).
In the laboratory processed specimens, all restorations initially revealed nearly 100%
gap-free margins (p>0.05; Mann-Whitney U-test). After TML alone, continuous
margins dropped to 87-90% in enamel and 55-66% in dentin (p<0.05; Wilcoxon test;
in dentin with a significantly higher portion of gap-free margins for Syntac/Tetric
Ceram; p<0.05; Mann-Whitney U-test). After water storage for 6 years alone, gap-
free margins dropped to 97-99% in enamel and 67-75% in dentin (p<0.05; Wilcoxon
test; in dentin with a significantly higher portion of gap-free margins for
Syntac/Tetric Ceram; p<0.05; Mann-Whitney U-test). After water storage and TML,
Long-term degradation of enamel and dentin bonds: 6-year results in vitro vs. in vivo
37
marginal quality in enamel ranged from 85-87%, and in dentin 42-52% (p<0.05;
Wilcoxon test; in dentin with a significantly higher portion of gap-free margins for
Syntac/Tetric Ceram; p<0.05; Mann-Whitney U-test). Thermomechanical loading
had a more detrimental effect on marginal quality than 6 years water storage alone
(p<0.05).
In vitro In vivo
Materials Substrate Initial TML WS WS +
TML
Initial 6 years
Syntac +
Tetric Ceram
Enamel 100 90(3) 99 (2) 87 (8) 90 (9) 80 (18)
Dentine 100 66 (11) 75 (10) 52 (16) n.a. n.a.
Solobond M +
Grandio
Enamel 100 87 (4) 97 (2) 85 (9) 86 (10) 74 (19)
Dentine 98 (2) 55 (14) 67 (11) 42 (14) n.a. n.a.
Table 3.3 Overview of results with percentages of gap-free margins in % (SD). TML: Thermomechanical loading; WS: Water storage for 2190 days.
For the in vivo replicas, only marginal quality in enamel was recordeable by the
impression/replica technique. In enamel, continuous margins were initially at 86-
90% and after 6 years of clinical service at 74-80%, however, whether initially (1-
3%) nor after 6 years (4-5%) severe gap formation was found. Non-continuous
margins were attributed to clinical wear and consecutive negative step/crevice
formation/marginal fractures having been slightly more pronounced for Grandio
(p<0.05; Mann-Whitney U-test). For proximal margins being located in dentin,
clinical observations neither revealed severe staining nor secondary caries formation
over 6 years, so the absence of enamel at the bottom of the proximal box did not
affect results.
Chapter 3
38
Discussion
The idea to compare in vitro and in vivo outcome of resin-based composite
restorations is not new. As first approach in the history of the field, Abdalla and
Davidson published their “comparison of the marginal integrity of in vitro and in
vivo Class II composite restorations” in 1993, dealing with microleakage scores in
both laboratory and ex vivo specimens.1 In this paper, microleakage was
substantially more severe in the in vivo group, so the unanimous conclusion was that
it may not be possible to reliably predict clinical behavior of bonded restorations in
the lab. In this context, Peumans et al. reported the clinical outcome of different
adhesives in non-carious cervical lesions, because Class V setups do not provide
macromechanical retention but considerable amounts of dentin margins. However,
Class V trials completely fail to prove whether bonded resin-based composites may
compete with amalgam in posterior cavities under occlusal load. Although in Class II
setups macro-retention is normal, at least in replacement cavities and considerably
less dentin margins are routinely found, there are also advantages. Recording of
postoperative hypersensitivities is a valid instrument to estimate dentin seal, and
secondary caries is a well-suited indicator of loss of bonding performance, especially
in proximal areas of the restorations.
Former publications of our workgroup already dealt with resin composites and their
corresponsing adhesives in both aspects, in vitro and in vivo. The first one aimed to
elucidate in vitro performance of resin composites focusing on microtensile bond
strengths to enamel and dentin, flexural fatigue behavior, and wear behavior.10
Ariston pHc and Solitaire showed some differences compared to other contemporary
resin composites, Ariston provided significantly less adhesion to enamel and dentin,
Solitaire provided inferior flexural fatigue behavior.10 The corresponding part
showed clinical findings of the previously described resin composites being
completely unacceptable.18 So in both cases, clinical performance of resin
composites in Class II cavities was predictable from laboratory results.
However, the literature in the field of adhesive dentistry still requires some evidence
given from in vitro – in vivo comparisons. Based on the previously described
prospective clinical trial, also in vitro experiments with the identical materials were
performed. As artificial aging protocol six years water storage was chosen with and
without thermomechanical loading. TML setups are frequently used to mimic the
clinical situation, however, it is unclear how many cycles mean how much lifetime in
Long-term degradation of enamel and dentin bonds: 6-year results in vitro vs. in vivo
39
the mouth of the patient. Therefore, setups and cycle numbers are subjected to a wide
variation from 4,000 to 1.2 million cycles combined with separate or simultaneous
thermocycling. Derived from Swiss data from the 1980’s, it was widely accepted that
in vitro fatiguing of resin-tooth interfaces for 1.2 million cycles may be somewhat
equivalent to 5 years of clinical service.3,7,20,21 Even for fatigue simulations on core
build-up restorations as postendodontic restorations, this benchmark was used from
time to time.25,26. However, the basis of this approach was just counting chewing
cycles and not a true in vitro – in vivo comparisons of dental restoratives under
simulated and clinical load.
A previous study of our workgroup demonstrated that 100,000 load cycles combined
with 2,500 thermocycles was able to simulate clinical behavior of a 2-year period for
Class I cavities restored with bonded resin composites.11 A distinct advantage for
etch-and-rinse adhesives compared to self-etch adhesives was also shown.11
Also the results of the present in vitro – in vivo comparison revealed a certain
relationship between preclinical and clinical observations. Percentage of gap-free
margins was chosen as a main criterion, because this way it was possible also to
include clinical crevices without detectable gap formations. The present results
indicate that TML alone led to a higher loss of marginal integrity than 6 years’ water
storage (Table 3.3). On the other hand, a combined WS/TML scenario exhibited the
most pronounced effect on marginal quality over time. Nevertheless, in vitro and in
vivo results show a certain similarity. However, this is also attributed to the fact that
gap-free irregularities were also included in “gap-free” margins. Otherwise,
completely perfect margins in vivo (i.e. without any crevice or negative step
formation were ~55% initially and 20-30% after 6 years of clinical service.
Thus, marginal quality prediction is possible from laboratory findings, however,
marginal integrity is only one among several crucial factors responsible for clinical
success or clinical failure over time, meaning that more interfacial gaps after thermal
and mechanical stressing in vitro raise the probability of the same scenario to occur
under clinical circumstances in the oral cavity. However, some important
publications about secondary caries clearly demonstrated that the presence of
marginal gaps in vivo do not necessarily have to be accompanied with secondary
caries.16,17
Chapter 3
40
Altogether, a particular problem with adhesive restorations remains in general: A
given combination of adhesive and resin composite may obtain high percentages of
gap-free margins in vitro, so it may consequently have also a promising clinical
behavior related to marginal quality. The residual question is: What percentage of
marginal quality may be promising or below what borderline is there no guarantee
for clinical success? In the present case, in both groups (Syntac/Tetric Ceram vs.
Solobond M/Grandio) the in vitro results were promising, so also clinical outcome
was sufficient. For inferior materials, not enough data are collected and furthermore
ethically doubtful.
Facing the ultimate question, it has to be taken into account that several studies
dealing with evaluated marginal quality of restorations in vitro were designed in
order to elucidate primarily experimental questions where clinical trials would never
pass an ethics committee. In these cases only in vitro studies are possible, showing
appropriate ways for clinical application of dental materials. Facing different
laboratory approaches to predict clinical behavior such as bond strength testing or
microleakage assessment, thermomechanical loading with a SEM marginal analysis
still is the setup being closest to the clinical situation, however, it is still the most
extensive and time-consuming way of evaluating restorative materials.
Long-term degradation of enamel and dentin bonds: 6-year results in vitro vs. in vivo
41
References
1. Abdalla AI, Davidson CL. Comparison of the marginal integrity of in vivo and
in vitro Class II composite restorations. J Dent 1993;21:158-162.
2. Baratieri LN, Ritter AV. Four-year clinical evaluation of posterior resin-based
composite restorations placed using the total-etch technique. J Esthet Restor
Dent 2001;13:50-57.
3. Bortolotto T, Onisor I, Krejci I. Proximal direct composite restorations and
chairside CAD/CAM inlays: Marginal adaptation of a two-step self-etch
adhesive with and without selective enamel conditioning. Clin Oral Investig
2007;11:35-43.
4. da Cunha Mello FS, Feilzer AJ, de Gee AJ, Davidson CL. Sealing ability of
eight resin bonding systems in a Class II restoration after mechanical fatiguing.
Dent Mater 1997;13:372-376.
5. De Munck J, Van Landuyt K, Peumans M, Poitevin A, Lambrechts P, Braem
M, Van Meerbeek B. A critical review of the durability of adhesion to tooth
tissue: methods and results. J Dent Res 2005;84:118-132.
6. De Munck J, Van Meerbeek B, Yoshida Y, Inoue S, Vargas M, Suzuki K,
Lambrechts P, Vanherle G. Four-year water degradation of total-etch adhesives
bonded to dentin. J Dent Res 2003;82:136-140.
7. Dietschi D, Herzfeld D. In vitro evaluation of marginal and internal adaptation
of class II resin composite restorations after thermal and occlusal stressing. Eur
J Oral Sci 1998;106:1033-1042.
8. Feilzer AJ, de Gee AJ, Davidson CL. Setting stress in composite resin in
relation to configuration of the restoration. J Dent Res 1987;66:1636-1639.
9. Ferrari M, Yamamoto K, Vichi A, Finger WJ. Clinical and laboratory
evaluation of adhesive restorative systems. Am J Dent 1994;7:217-219.
10. Frankenberger R, Garcia-Godoy F, Lohbauer U, Petschelt A, Krämer N.
Evaluation of resin composite materials. Part I: in vitro investigations. Am J
Dent 2005;18:23-27.
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11. Frankenberger R, Krämer N, Lohbauer U, Nikolaenko SA, Reich SM.
Marginal integrity: is the clinical performance of bonded restorations
predictable in vitro? J Adhes Dent 2007;9 Suppl 1:107-116.
12. Frankenberger R, Krämer N, Petschelt A. Technique sensitivity of dentin
bonding: effect of application mistakes on bond strength and marginal
adaptation. Oper Dent 2000;25:324-330.
13. Frankenberger R, Reinelt C, Petschelt A, Krämer N. Operator vs. material
influence on clinical outcome of bonded ceramic inlays. Dent Mater
2009;25:960-968.
14. Frankenberger R, Strobel WO, Lohbauer U, Krämer N, Petschelt A. The effect
of six years of water storage on resin composite bonding to human dentin. J
Biomed Mater Res B Appl Biomater 2004;69:25-32.
15. Frankenberger R, Tay FR. Self-etch vs etch-and-rinse adhesives: effect of
thermo-mechanical fatigue loading on marginal quality of bonded resin
composite restorations. Dent Mater 2005;21:397-412.
16. Kidd EA, Beighton D. Prediction of secondary caries around tooth-colored
restorations: a clinical and microbiological study. J Dent Res 1996;75:1942-
1946.
17. Kidd EA, Toffenetti F, Mjör IA. Secondary caries. Int Dent J 1992;42:127-138.
18. Krämer N, Garcia-Godoy F, Frankenberger R. Evaluation of resin composite
materials. Part II: in vivo investigations. Am J Dent 2005;18:75-81.
19. Krämer N, Reinelt C, Richter G, Petschelt A, Frankenberger R. Nanohybrid vs.
fine hybrid composite in Class II cavities: clinical results and margin analysis
after four years. Dent Mater 2009;25:750-759.
20. Lutz F, Krejci I. Resin composites in the post-amalgam age. Compend Contin
Educ Dent 1999;20:1138-44, 1146, 1148.
21. Lutz F, Krejci I, Barbakow F. Quality and durability of marginal adaptation in
bonded composite restorations. Dent Mater 1991;7:107-113.
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22. Manhart J, Chen H, Hamm G, Hickel R. Buonocore Memorial Lecture. Review
of the clinical survival of direct and indirect restorations in posterior teeth of
the permanent dentition. Oper Dent 2004;29:481-508.
23. Mjör IA. The reasons for replacement and the age of failed restorations in
general dental practice. Acta Odontol Scand 1997;55:58-63.
24. Mjör IA, Toffenetti F. Secondary caries: a literature review with case reports.
Quintessence Int 2000;31:165-179.
25. Naumann M, Preuss A, Frankenberger R. Load capability of excessively flared
teeth restored with fiber-reinforced composite posts and all-ceramic crowns.
Oper Dent 2006;31:699-704.
26. Needleman I, Worthington H, Moher D, Schulz K, Altman DG. Improving the
completeness and transparency of reports of randomized trials in oral health:
the CONSORT statement. Am J Dent 2008;21:7-12.
27. Nikolaenko SA, Lohbauer U, Roggendorf M, Petschelt A, Dasch W,
Frankenberger R. Influence of c-factor and layering technique on microtensile
bond strength to dentin. Dent Mater 2004;20:579-585.
28. Opdam NJ, Roeters FJ, Feilzer AJ, Verdonschot EH. Marginal integrity and
postoperative sensitivity in Class 2 resin composite restorations in vivo. J Dent
1998;26:555-562.
29. Ottenga ME, Mjor I. Amalgam and composite posterior restorations:
curriculum versus practice in operative dentistry at a US dental school. Oper
Dent 2007;32:524-528.
30. Peumans M, Kanumilli P, De MJ, Van Landuyt K., Lambrechts P, Van
Meerbeek B. Clinical effectiveness of contemporary adhesives: A systematic
review of current clinical trials. Dent Mater 2005;21:864-881.
31. Roulet JF. Marginal integrity: clinical significance. J Dent 1994;22 Suppl 1:S9-
12.
32. Tay FR, Frankenberger R, Carvalho RM, Pashley DH. Pit and fissure sealing.
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Bonding of bulk-cured, low-filled, light-curing resins to bacteria-contaminated
uncut enamel in high c-factor cavities. Am J Dent 2005;18:28-36.
33. Van Meerbeek B, Kanumilli P, De Munck J, Van Landuyt K, Lambrechts P,
Peumans M. A randomized controlled study evaluating the effectiveness of a
two-step self-etch adhesive with and without selective phosphoric-acid etching
of enamel. Dent Mater 2005;21:375-383.
34. Van Meerbeek B, Kanumilli PV, De Munck J, Van Landuyt K, Lambrechts P,
Peumans M. A randomized, controlled trial evaluating the three-year clinical
effectiveness of two etch & rinse adhesives in cervical lesions. Oper Dent
2004;29:376-385.
35. Van Meerbeek B, Perdigao J, Lambrechts P, Vanherle G. The clinical
performance of adhesives. J Dent 1998;26:1-20.
36. Van Meerbeek B, Peumans M, Gladys S, Braem M, Lambrechts P, Vanherle
G. Three-year clinical effectiveness of four total-etch dentinal adhesive
systems in cervical lesions. Quintessence Int 1996;27:775-784.
45
CHAPTER 4
Fatigue behavior of dental resin composites: Flexural fatigue in vitro vs. six years in vivo
Chapter 4
46
Introduction
During the last decades, resin-based composite materials were optimized with a
special focus on amalgam replacement.1-4 Thus, resin composites were more and
more improved for application even in occlusally stressed areas.5-10 In order to
simulate clinical conditions in the laboratory, it is important to observe fatigue
phenomena as an important factor during biodegradation processes of dental
biomaterials.11-15
In former times that have been characterized by less effective adhesive technology
and higher polymerization stresses generated by older resin composite materials, gap
formation and recurrent decay were the predominant reason for failures of bonded
resin composite restorations.5,16 Today, this is still true, but fatigue fractures after
several years under clinical load gain importance as reason for failure.2-4, 9,10,22
Fatigue in dental restoratives is influenced by corrosive water attack at 37°C and by
subcritical cyclic masticatory forces having been estimated to be 5-20 MPa.6,17,18
Contemporary approaches to fatigue principles describe fracture processes in three
stages: crack initiation, slow crack growth, fast fracture.6,17,18 Especially crack
initiation time and slow crack growth time are determining fatigue resistance of an
individual material. Crack initiation originates from surface and subsurface
microcracks, porosities, or filler particles.11,14,15,19 Cyclic loading is able to drive a
crack, and additional water exposure causes a variety of further weakening effects on
resin composite materials, i.e. degradation of the filler–matrix interface, swelling, or
visco-elastic effects on the matrix which all are able to accelerate slow crack
growth.11,14,15,19
Today it is still not fully understood whether and to what extent we are able to predict
clinical behavior of dental biomaterials such as resin composites based on in vitro
research. Therefore, the aim of this study was to compare fatigue behavior of two
different resin composites using an array of laboratory parameters (Young's modulus,
flexural strength, flexural fatigue limit) and analyze resin composite restorations in the
course of a randomized prospective clinical long-term trial over 6 years. This is the
maxiumum approach to thoroughly evaluate dental materials simultaneously in vitro
and in vivo.
Fatigue behavior of dental resin composites: Flexural fatigue in vitro vs. six years in vivo
47
Materials and Methods
Grandio
Grandio (shade A3, Voco, Germany), a nanofilled hybrid resin composite, was used in
this study. The resin matrix consisted of bisphenol glycidyl methacrylate (BisGMA)
and triethylene glycol dimethacrylate (TEGDMA), mixed in a ration of 3:1. Further
71.4 vol% (87 wt%) inorganic fillers were compounded, being 30% nanosized fillers.
Camphoroquinone served as photoinitiator. Grandio is clinically indicated as a
universal composite for anterior and posterior restorations.
Tetric Ceram
The light-curing dental restorative Tetric Ceram (shade A3, Ivoclar Vivadent,
Liechtenstein) was used in this study. The material was based on a bisphenol glycidyl
methacrylate (BisGMA)/urethane dimethacrylate (UDMA)/triethylene glycol
dimethacrylate (TEGDMA) resin matrix, with camphoroquinone as photoinitiator and
60 vol % (78 wt%) inorganic filler content. Tetric Ceram is clinically indicated as a
universal fine particle hybrid resin composite for anterior and posterior restorations.
Specimen preparation
Rectangular specimens with the dimension 2 x 2 x 25 mm were produced using a
metal/glass mold and light-curing on five overlapping spots of 8 mm diameter. The
upper and lower side of the bar were cured with a commercial halogen light curing
unit (Elipar Trilight (750 mW/ cm²), 3M Espe, Germany). The illumination time on a
single spot was 40s. The procedure followed the manufacturers’ recommendation and
ISO 4049 standard. The specimen flanges were ground under an angle of 45° using
SiC paper (1200 grit). All specimens were stored for 14 days in distilled water at
37°C, deviating from the ISO 4049 standard.
Elastic Modulus (EM)
To determine the elastic response of the composites, the Young’s moduli were
calculated from load-displacement curves in a four-point bending test setup. The
specimens (n=10) were positioned in the test rig (distance between the lower supports:
20mm, upper fins: 10mm) of a universal testing machine (Zwick Z2.5, Zwick, Ulm,
Germany) and loaded up to 20 MPa with a crosshead speed of 0.75 mm/minute. By
the linear-elastic relationship between stress (in the range between 10 to 20 MPa) and
Chapter 4
48
strain the EM was calculated. An extensometer served to measure the true deflection
(system compliance) directly at the lower side of the specimen.
Fracture strength (FS)
To evaluate the initial flexural strength (FS), the four-point bending test was used (n =
15). Fifteen bars of each material were brought into the four-point test rig and loaded
until fracture with a crosshead speed of 0.75 mm/minute in a universal testing
machine (Z 2.5, Zwick, Germany).6,17,18,22 The measurements were carried out in
distilled water at 37°C.
Flexural Fatigue Limit (FFL)
The flexural fatigue limits (FFL) of the composite materials were determined for 105
cycles under equivalent test conditions at a frequency of 0.5 Hz (n=25). The
“staircase” approach was used for fatigue evaluation.12,13,20,22 For every cycle the
stress alternated between 1 MPa and the maximum stress. Tests were conducted
sequentially, with the maximum applied stress in each succeeding test being increased
or decreased by a fixed increment (5 MPa) of stress, according to whether the
previous test resulted in failure or not. The first specimen was tested at approximately
50% of the initial flexural strength value. As the data are cumulated around the mean
stress, the number of specimens required is less than with other methods (n=25). The
test stopped at a certain level below which no further failure occured. 6,12,13-15
The mean flexural fatigue limit (FFL) was determined using Eq. 1 and standard
deviation, using Eq. 2, respectively:
5.00
i
i
n
indXFFL (1)
029.062.1
2
22
i
iii
n
innindSD (2)
where X0 is the lowest stress level considered in the analysis and d is the fixed stress
increment.6,13,17 To determine the FFL, the analysis of the data was based on the least
frequent event (failures versus non failures). In Eq. 1 a negative sign was used when
Fatigue behavior of dental resin composites: Flexural fatigue in vitro vs. six years in vivo
49
the analysis was based on failures. The lowest stress level considered was designated
as i = 0, the next as i = 1, and so on, and ni was the number of failures or non-failures
at the given stress level. 6,13,17
Statistical treatment
The strength data (FS and FFL) were statistically treated using a one-way ANOVA
test followed by a modified LSD post-hoc routine (p < 0.05).
Clinical study
In the course of a randomized clinical study with approval of a local ethics committee
(University of Erlangen, Germany), 30 subjects (23 female, 7 male, mean age 32.9 (24-
59) years) with a minimum of two restorations to be placed in different quadrants
received at least two different Class II restorations (52 MO/OD, 16 MOD or more
surfaces, no cusp replacements) in a random decision.26 Thirty six Grandio restorations
were bonded with Solobond M (Voco) and 32 Tetric Ceram restorations were bonded
with Syntac (Ivoclar Vivadent). The cavities were cut using coarse diamond burs under
profuse water cooling (80 µm diamond, Komet, Lemgo, Germany), and finished with a
25 µm finishing diamond. Inner angles of the cavities were rounded and the margins
were not bevelled. After cleaning and drying under rubber dam isolation
(Coltene/Whaledent Inc., Altstätten, Switzerland), adhesive procedures were performed
with Solobond M (2-step etch-and-rinse adhesive) and Syntac (4-step etch-and-rinse
adhesive). The resin composite materials were applied into the cavity in layers of
approximately 2 mm thickness and adapted to the cavity walls with a plugger. Each
layer was light cured for 40 s (Elipar Trilight, 3M Espe, Seefeld, Germany). The
occlusal region was sculpted as exactly as possible under intraoral conditions, avoiding
visible overhangs. The light-emission window was placed as close as possible to the
cavity margins. The intensity of the light was checked periodically with a radiometer
(Demetron Research Corp., Danburg, CT, USA) and was found to be consistently above
650 mW/cm2. Visible overhangs were removed with a scaler and the rubber dam was
removed. Contacts in centric and eccentric occlusion were checked with foils (Roeko,
Langenau, Germany) and adjusted with finishing diamonds (Komet Dental, Lemgo,
Germany), shaped with flexible discs (3M Dental, St. Paul, USA), super-fine discs (3M
Dental, St. Paul, USA) and polishing brushes (Hawe-Neos Dental, Bioggio,
Switzerland). A fluoride varnish (Elmex Fluid, GABA, Lörrach, Germany) was applied
with a foam pellet (Pele-Tim, Voco, Cuxhaven, Germany) to complete the treatment.
Chapter 4
50
Impressions (Dimension Penta and Garant, 3M ESPE, Seefeld, Germany) were taken at
baseline, after 4 and 6 years and were used to make epoxy replicas (Alpha Die, Schütz
Dental, Germany) for x30 magnification cast analysis under a scanning electron
microscope (SEM) evaluating fatigue characteristics such as voids, chippings or cracks
within the resin composite, and 22 of them (n=11 per group) were subjected to SEM
margin analysis at x200. The replicas with the longest evaluable margins were selected
randomly. All in vitro and in vivo replicas were mounted on aluminum stubs, sputter-
coated with gold and examined under a SEM (Leitz ISI 50, Akashi, Tokyo, Japan) at
x200 magnification. SEM examination was performed by one operator having
experience with quantitative margin analysis who was blinded to the restorative
procedures. The marginal quality between resin composite and enamel was expressed as
percentage of the entire judgeable margin length, i.e. margins having been accessible by
the impression material in vivo. Marginal qualities were classified according to the
criteria “continuous/gap-free margin” and “gap/irregularity” for another study, here the
focus was set on marginal breakdown and cracks. Non-judgeable parts and artifacts
were excluded. Afterwards the percentage of “marginal fracture areas” in relation to the
individual judgeable margin was calculated as marginal fracture score. For better
comparison with in vitro results, gap-free margins were scored whether there was a
negative step or not.
Statistical analysis was performed using SPSS 14.0 (SPSS Inc., Chicago, IL, USA).
As the majority of groups in each of the two investigations did not exhibit normal data
distribution (Kolmogorov-Smirnov test), non-parametric tests were used (Wilcoxon
matched-pairs signed-ranks test, Mann-Whitney-U test) for pairwise comparisons at
the 95% significance level.
Results
Results of the laboratory part are displayed in Table 1. It was shown that Grandio
exhibited a significantly higher elastic modulus (p<0.05) and flexural fatigue limit
(p<0.05). Initial fracture strengths were not significantly different (p>0.05). Results
of the clinical investigation are shown in Tables 3 and 4. Irrespective of the resin
composite used, significant changes over time were found for all criteria applied in
clinical examinations (Friedman test; p<0.05). The main reason for the degradation
of the occlusal surface of the restorations was an increased surface roughness (41%
Fatigue behavior of dental resin composites: Flexural fatigue in vitro vs. six years in vivo
51
after 4 and 27% after 6 years) and more chipping especially in the proximal ridge
area (36% after 4 and 35 % after 6 years; Fig. 2). Voids were obvious mainly after 6
years (clinically 44% and SEM 73 %; Table 3 and 4). Except for the criterion “wear”
after 6 years (Pearson correlation coefficient 0.671) no correlation was calculated
between the clinical and cast evaluation (p>0.05; two-tailed correlation). Neither
restorative materials nor localization of the restorations (upper or lower jaw) had a
significant influence on the surface degradation at baseline and after 4/6 years
(p>0.05; Mann‐Whitney U-test). However, molar restorations performed worse than
premolar restorations regarding the clinical criterion “wear” after both 4 and 6 years
(premolars: 22% bravo after 4 and 44% after 6 years vs. molars: 61% bravo after 4
and 69% after 6 years).
Criteria and results of the x30 magnification cast analysis under the SEM are
displayed in Table 4. Here also, no significant differences were computed between the
materials Grandio and Tetric Ceram. Only in the x200 SEM analysis of restoration
margins, marginal breakdown areas were more often recorded for Tetric Ceram
(7.9%) vs. Grandio (4.8%). Examples for clinical images and corresponding SEM
pictures are explained in Figures 1-5. Predominant findings in both species of
investigations were slightly exposed restoration margins after 6 years of clinical
service due to mainly wear in the contact free areas (CFA; Figures 1b, 2b, 3b, 4b) and
more roughened surfaces in the occlusal contact areas (OCA).
Discussion
Biomaterials labs daily try to simulate clinical conditions in order to predict clinical
behavior of dental biomaterials.5,20-23 This is the only and most important justification
of the existence of this kind of laboratory. Without clinical relevance, what should be
the reason for in vitro research?
Beside other co-factors for clinical success with resin-based composites such as
marginal integrity, wear, biocompatibility and absence of postoperative
hypersenstivities2,3,9,10,24,25, fatigue is a major factor during biodegradation of
restorative materials. Fatigue loading has gained importance in materials science not
only regarding adhesion,5,22-24,26 since even for restorative materials the initially high
flexural strength values suffered a reduction of 50% after fatigue loading.
Chapter 4
52
The chosen in vitro setup of the present study was shown to give reliable and
reasonable results in several studies with an array of different classes of
materials.14,15,30-32 On first sight it may be awkward to evaluate a restorative material
as simple beam in a 4-point bending device, since the same material is always
adhesively bonded under clinical conditions. However, results from previous studies
as well as the present results demonstrate that FFL analysis of dental biomaterials
gives important results for their intraoral use in stress-bearing restorations.14,15,30-32
Facing the present results in both aspects in vitro and in vivo, it is crucial to achieve
equal or even similar test conditions in both setups.
One fundamental point here is light polymerization. On one hand, we had to stick to
previously published curing protocols to get comparable results to former
investigations;6,13,17 on the other hand, light-curing under clinical conditions should at
least be achievable. So it might be a consequence that in vitro specimens are still more
intensively light-cured than the same materials having been applied in vivo. The same
is true for storage times in vitro, so we used the well-established protocol of 2 weeks
water storage6,13,17 whereas loading began immediately intraorally.
Another critical point in the present simulation of clinical circumstances is the in vitro
setup in general. In vitro we used simple beams having been mechanically loaded as
bars and not as bonded resin composite restorations being stabilized inside the tooth.
Here, thermomechanical loading may be much closer to the real clinical situation,
however, also in a chewing simulation chamber with more complex and individually
styled restorations in natural teeth forces are more complex to handle.23
The normal way of testing dental biomaterials is to conduct preclinical issues first and
then carry out clinical trials. However, when in vitro and in vivo research is carried
out simultaneously as in the present paper, an appropriate comparison of both ways of
investigations is possible.4,23,26 So since 1998, we decided to perform in vitro and in
vivo research with the same materials simultaneously with both resin composites and
ceramic materials. This may be the most appropriate way to explain what happened
clinically and why it happened as well. Furthermore it is easier to determine
predictable parameters in the laboratory.
Compared to other classes of restorative materials such as glass ionomer cements,
both resin composites under investigation provided sufficient initial flexural strengths
Fatigue behavior of dental resin composites: Flexural fatigue in vitro vs. six years in vivo
53
of >100 MPa. However, both Young’s modulus and flexural fatigue limit were
significantly higher for Grandio. In the present study, FFL of investigated materials
was 63 MPa for Grandio and 44 MPa for Tetric Ceram. These findings were not
statistically different at the initial stage of flexural strength. After mechanical fatigue,
the FFL of Grandio was 55% of the initial flexural strength, whereas Tetric Ceram
dropped to 45% of its initial flexural strength values. Regarding both aspects,
physicochemical characteristics were slightly better for Grandio which also exhibited
a somewhat increased filler load of 87%wt vs. 78%wt in Tetric Ceram. Facing the
overall clinical performance of both materials, slightly superior materials
characteristics for Grandio did not result in a significantly better clinical outcome, at
least after 6 years of clinical service. Only when dental restorative materials have
flexural fatigue limits of less than 20 MPa, it seems to be critical for clinical survival
with more frequent catastrophic bulk fractures even after considerably shorter clinical
observation periods.4 In a previous study under identical test conditions in vitro as
well as in vivo, Solitaire provided a FFL of 18 MPa which lead to unacceptably high
marginal and bulk fracture rates in vivo in the course of a prospective clinical study.4
Finally, the significantly higher FFL for Grandio when compared to Tetric Ceram led
to clinical consequences having been detected under the SEM during the marginal
quality evaluation: Grandio restorations exhibited significanlty less marginal
breakdown (4.8%) than Tetric Ceram restorations (7.9%). Although Grandio
restorations showed inferior marginal quality in a previous clinical trial,26 they
performed slightly better according to marginal fatigue characteristics in the present
investigation. However, these are microscopic findings suffering limited clinical
impact for the present observation period of 6 years when it comes to clinical survival
as the major criterion.
Up to now, wear was the predominantly detected degradation factor over time.14,15,25
In contrast, the influence of the clinical operator is still a major factor for clinical
success, maybe more than the difference between an FFL of 40 MPa vs. 50 MPa.33
Chapter 4
54
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dental resin composites. Dent Mater 2005;21:1150-1157.
2. Hickel R, Manhart J, Garcia-Godoy F. Clinical results and new developments
of direct posterior restorations. Am J Dent 2000;13:41D-54D.
3. Hickel R, Manhart J. Longevity of restorations in posterior teeth and reasons
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4. Krämer N, Garcia-Godoy F, Frankenberger R. Evaluation of resin composite
materials. Part II: in vivo investigations. Am J Dent 2005;18:75-81.
5. Lambrechts P, Braem M, Vanherle G. Buonocore memorial lecture. Evaluation
of clinical performance for posterior composite resins and dentin adhesives.
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6. Lohbauer U, von der Horst T, Frankenberger R, Krämer N, Petschelt A.
Flexural fatigue behavior of resin composite dental restoratives. Dent Mater
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7. Manhart J, Kunzelmann KH, Chen HY, Hickel R. Mechanical properties and
wear behavior of light-cured packable composite resins. Dent Mater
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8. Manhart J, Chen HY, Hickel R. The suitability of packable resin-based
composites for posterior restorations. J Am Dent Assoc 2001;132:639-645.
9. Manhart J, Chen H, Hamm G, Hickel R. Buonocore Memorial Lecture. Review
of the clinical survival of direct and indirect restorations in posterior teeth of
the permanent dentition. Oper Dent 2004;29:481-508.
10. Manhart J, Chen HY, Hickel R. Clinical evaluation of the posterior composite
Quixfil in class I and II cavities: 4-year follow-up of a randomized controlled
trial. J Adhes Dent 2010;12:237-243.
11. Braem M, Lambrechts P, Van Doren V, Vanherle G. The impact of composite
structure on its elastic response. J Dent Res 1986;65:648-653.
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12. Braem M, Davidson CL, Vanherle G, Van Doren V, Lambrechts P. The
relationship between test methodology and elastic behavior of composites. J
Dent Res 1987;66:1036-1039.
13. Braem MJ, Davidson CL, Lambrechts P, Vanherle G. In vitro flexural fatigue
limits of dental composites. J Biomed Mater Res 1994;28:1397-1402.
14. Keulemans F, Palav P, Aboushelib MM, van Dalen A, Kleverlaan CJ, Feilzer
AJ. Fracture strength and fatigue resistance of dental resin based composites.
Dent Mater 2009;25:1433-1441.
15. Turssi CP, Ferracane JL, Ferracane LL. Wear and fatigue behavior of nano-
structured dental resin composites. J Biomed Mater Res B Appl Biomater
2006;78:196-203.
16. Wilder AD, Jr., May KN, Jr., Bayne SC, Taylor DF, Leinfelder KF. Seventeen-
year clinical study of ultraviolet-cured posterior composite Class I and II
restorations. J Esthet Dent 1999;11:135-142.
17. Lohbauer U, Frankenberger R, Krämer N, Petschelt A. Time-dependent
strength and fatigue resistance of dental direct restorative materials. J Mater
Sci Mater Med 2003;14:1047-1053.
18. Lohbauer U, Rahiotis C, Krämer N, Petschelt A, Eliades G. The effect of
different light-curing units on fatigue behavior and degree of conversion of a
resin composite. Dent Mater 2005;21:608-615.
19. Abe Y, Braem MJ, Lambrechts P, Inoue S, Takeuchi M, Van MB. Fatigue
behavior of packable composites. Biomaterials 2005;26:3405-3409.
20. Drummond JL, Lin L, Al-Turki LA, Hurley RK. Fatigue behaviour of dental
composite materials. J Dent 2009;37:321-330.
21. Feilzer AJ, de Gee AJ, Davidson CL. Setting stress in composite resin in
relation to configuration of the restoration. J Dent Res 1987;66:1636-1639.
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22. Frankenberger R, Garcia-Godoy F, Lohbauer U, Petschelt A, Krämer N.
Evaluation of resin composite materials. Part I: in vitro investigations. Am J
Dent 2005;18:23-27.
23. Frankenberger R, Krämer N, Lohbauer U, Nikolaenko SA, Reich SM.
Marginal integrity: is the clinical performance of bonded restorations
predictable in vitro? J Adhes Dent 2007;9 Suppl 1:107-116.
24. De Munck J, Van Landuyt K, Peumans M, Poitevin A, Lambrechts P, Braem
M, Van Meerbeek B. A critical review of the durability of adhesion to tooth
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25. Gaengler P, Hoyer I, Montag R, Gaebler P. Micromorphological evaluation of
posterior composite restorations - a 10-year report. J Oral Rehabil
2004;31:991-1000.
26. Garcia-Godoy F, Krämer N, Feilzer AJ, Frankenberger R. Long-term
degradation of enamel and dentin bonds: 6-year results in vitro vs. in vivo.
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27. Braem MJ, Lambrechts P, Gladys S, Vanherle G. In vitro fatigue behavior of
restorative composites and glass ionomers. Dent Mater 1995;11:137-141.
28. Krämer N, Reinelt C, Garcia-Godoy F, Taschner M, Petschelt A,
Frankenberger R. Nanohybrid composite vs. fine hybrid composite in extended
class II cavities: clinical and microscopic results after 2 years. Am J Dent
2009;22:228-234.
29. Krämer N, Reinelt C, Richter G, Petschelt A, Frankenberger R. Nanohybrid vs.
fine hybrid composite in Class II cavities: clinical results and margin analysis
after four years. Dent Mater 2009;25:750-759.
30. Drummond JL. Cyclic fatigue of composite restorative materials. J Oral
Rehabil 1989;16:509-520.
31. Drummond JL, Bapna MS. Static and cyclic loading of fiber-reinforced dental
resin. Dent Mater 2003;19:226-231.
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57
32. Ferracane JL, Condon JR. In vitro evaluation of the marginal degradation of
dental composites under simulated occlusal loading. Dent Mater 1999;15:262-
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33. Frankenberger R, Reinelt C, Petschelt A, Krämer N. Operator vs. material
influence on clinical outcome of bonded ceramic inlays. Dent Mater
2009;25:960-968.
Chapter 4
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59
CHAPTER 5
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years.
Chapter 5
60
Introduction
Although a prospective clinical trial is not an in vitro study as reflected by the topic of
the present thesis, clinical data are the one and only desirable comparison tool for
dental restorative materials. Moreover, they can be linked to preclinically evaluated in
vitro data. Therefore, it is important to compare the presented in vitro data with
clinical outcome of directly bonded dental biomaterials such as resin-based
composites.
Cavitated carious lesions are today predominantly restored by use of resin
composites.1-4 Durable adhesion to tooth hard tissues still is the fundamental
prerequisite for pit and fissure sealings, direct and indirect resin composites, and
bonded all-ceramic restorations 5-9. When adhesion mechanisms fail, gap formation
and secondary caries corroborate clinical success of restorations 10-13.
Bonding to enamel is clinically durable at least when the etch-and-rinse approach is
applied,1,6,12,14-16 dentin still provides inferior adhesion,8,9,13,17-20 but also clinically
acceptable sealing is obtainable to limit the occurrence of postoperative
hypersensitivity.4,6,7,11,12,21,22 Although bonded resin composites have proven to
durably seal dentin especially with multi-step adhesives,14,17,19,23-25 it is still unclear
whether it is possible to maintain a stable proximal seal in Class II cavities with
proximal margins extending beyond the amelocemental junction. In vitro studies give
varying results after thermomechanical loading and/or long-term storage, mostly with
distinct advantages for two- or three-step adhesives compared to simplified adhesive
systems.23,24,26-28 Prospective clinical trials remain ultimate instruments, but preclinical
in vitro investigations are still needed for experimental questions and preclinical
screening.17,26,29
One of the most severe problems of clinical trials of dental materials is apparent: while
affording acceptable results after some years of clinical service, there is a certain risk
that the adhesive and/or resin composite under investigation is not in the market
anymore.1,11,12,15,16,30,31 However, it is not a matter of course that this kind of clinical
trial reveals favorable results, so also catastrophic outcomes were observed when
fundamental prerequisites are neglected such as hygroscopic expansion or flexural
fatigue behavior.15 And it may be still true that, e.g. amalgam, may be superior to resin
composites for restoration of very extended defects,21
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years
61
Research and development of resin-based composites during the last decade generated
different subspecies of restorative materials, such as hybrid resin composites, fine
hybrid resin composites, nanohybrid resin composites, or even nano resin composites
(Filtek Supreme XTE, 3M ESPE, Seefeld, Germany). Especially the latter ones
entered the market with claims of less polymerization shrinkage, lowered shrinkage
stress and even higher wear resistance.32-37 In most of the cases, however, a truly better
clinical outcome is not proven. On the other hand, it is stated from recent in vivo
results that modern nano hybrid resin composite may provide an enamel-like wear
behavior.38,39
Therefore, the aim of this clinical trial was to investigate two different restorative
material systems (i.e. adhesive and resin composite) in extended Class II cavities over
6 years in order to observe differences between conventional (Tetric Ceram) and
partially nanofilled (Grandio) resin composites. The null-hypothesis tested was that
there would be no difference between the different resin composites with their
respective adhesives under investigation.
Methods and Materials
Patients selected for this study met the following criteria: 1) Absence of pain from the
tooth to be restored; 2) possible application of rubber dam during luting of restoration;
3) no further restorations planned in other posterior teeth; 4) high level of oral
hygiene; 5) absence of any active periodontal and pulpal desease; 6) restorations
required in two different quadrants (split mouth design).
Thirty patients (23 female, 7 male, mean age 32.9 (24-59) years) with a minimum of
two restorations to be replaced in different quadrants received at least two different
restorations in a random decision according to recommendations of the CONSORT
statement.40 Thirty-six Grandio restorations were bonded with Solobond M (Voco,
Cuxhaven, Germany) and 32 Tetric Ceram restorations were bonded with Syntac
(Ivoclar Vivadent, Schaan, Liechtenstein). All restorations (only Class II, 52 MO/OD,
16 MOD or more surfaces, no cusp replacements) were re-restorations made by one
dentist in a private practice (31 upper bicuspids, 12 upper molars, 14 lower bicuspids,
11 lower molars). Reasons for replacement were caries (n=19), insufficient esthetics
(n=2), and secondary caries (n=47). For all teeth receiving restorations, current X-rays
(within 6 months of the procedure) were present. After evaluating the radiographs, 53
Chapter 5
62
cavities (78%) were treated as caries profunda. Twenty-four cavities (35%) revealed
no enamel at the floor of the proximal box, while 33 cavities (49%) exhibited a
proximal enamel width of <0.5 mm.
All restorations were inserted in permanent vital teeth without pain symptoms. An
extension for prevention was disregarded for maximal substance protection; however,
the majority of restorations were previously prepared with undercuts for amalgam
retention. The cavities were cut using coarse diamond burs under profuse water cooling
(80 µm diamond, Komet, Lemgo, Germany), and finished with a 25 µm finishing
diamond. Inner angles of the cavities were rounded and the margins were not bevelled.
After cleaning and drying under rubber dam isolation (Coltene/Whaledent Inc.,
Altstätten, Switzerland), adhesive procedures were performed with Solobond M (2-step
etch-and-rinse adhesive) and Syntac (4-step etch-and-rinse adhesive). The resin
composite materials were applied into the cavity in layers of approximately 2 mm
thickness and adapted to the cavity walls with a plugger. Each layer was light cured for
40 seconds (Elipar Trilight, 3M ESPE, Seefeld, Germany). The occlusal region was
modeled as exactly as possible under intraoral conditions, avoiding visible overhangs.
The light-emission window was placed as close as possible to the cavity margins. The
intensity of the light was checked periodically with a radiometer (Demetron Research
Corp., Danburg, CT, USA) and was found to be constantly above 650 mW/cm2.
As soon as polymerization was completed, the surface of the restoration was checked for
defects and corrected when necessary. Visible overhangs were removed with a scaler
and the rubber dam was removed. Contacts in centric and eccentric occlusion were
checked with foils (Roeko, Langenau, Germany) and adjusted with finishing diamonds
(Komet Dental, Lemgo, Germany), shaped with flexible discs (3M Dental, St. Paul,
USA), super-fine discs (3M Dental, St. Paul, USA) and polishing brushes (Hawe-Neos
Dental, Bioggio, Switzerland). A fluoride varnish (Elmex Fluid, GABA, Lörrach,
Germany) was used to complete the treatment.
At the initial recall (baseline, i.e. within 2 weeks), and after 6 months, 1, 2, 4, and 6
years, all restorations were assessed according to the modified United States Public
Health Service (USPHS) criteria (Tables 5.1 and 5.2) by two independent
investigators using loupes with x3.5 magnification, mirrors, probes, bitewing
radiographs, impressions (Dimension Penta and Garant, 3M-ESPE, Seefeld,
Germany), and intraoral photographs. Replicas were collected for later marginal and
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years
63
wear analysis (studies in preparation). Recall assessments were not performed by the
clinician who initially placed the restorations.
Statistical appraisal was computed with SPSS for Windows XP 14.0 (SPSS Inc.,
Chicago, IL, USA). Statistical unit was one tooth, differences between groups were
evaluated using Mann-Whitney U-test, changes over time were calculated with the
Friedman test (p=0.05).
Modified
criteria Description
Analogous USPHS
criteria
“Excellent” Perfect
“alpha” “Good”
Slight deviations from ideal performance,
correction possible without damage to tooth or
restoration
“Sufficient”
Few defects, correction impossible without
damage to tooth or restoration.
No negative effects expected “bravo”
“Insufficient”
Severe defects, prophylactic removal for
prevention of severe failures “charlie”
“Poor” Immediate replacement necessary “delta”
Table 5.1: Evaluated clinical codes and criteria.
Results
The overall success rate was 100% after 6 years of clinical service, while drop out of
patients was 0%. Results of the clinical investigation are displayed in Tables 5.2‐5.7.
Neither restorative material nor localization of the restoration (upper or lower jaw)
had a significant influence on any criterion after 6 years (p>0.05; Mann‐Whitney U
test). However, molar restorations performed worse than premolar restorations
regarding marginal integrity (4 years), restoration integrity (6, 12, 24, 48 months),
and tooth integrity (4 and 6 years; Table 5.8). Irrespective of the resin composite
used, significant changes over time were found for all criteria applied in clinical
Chapter 5
64
examinations (Friedman test; p<0.05). Marginal integrity started with a major portion
of overhangs in all marginal areas having been detected until the 1‐year recall and
distinctly dropping afterwards (overhangs at baseline 44%; 6 months: 65%; 1 year:
47%; 2 years: 6%; 4 years: 4%; and 6 years: 3%). Beyond the 1‐year recall, more and
more negative step formations due to wear were detected (Table 5.5). This
phenomenon was earlier seen in molars (87 % bravo after 4 years) than in premolars
(51 % bravo after 4 years; Table 5.8a).
Baseline (n=68) 2 Years (n=68) 4 Years (n=68) 6 Years (n=68)
Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo
[%] [%] [%] [%] Date of investigation
1.2 months 24.4 months 49.2 months 73.3 months Criterion
Surface roughness
100
99 1
93 7
82 18
Color match 94 6 93 7 84 13 3 84 16
Marginal integrity
44 54 2
60 40
34 66
41 59
Tooth Integrity 91 9
40 47 13 29 56 15 31 48 21
Restoration Integrity 93 4 3 9 41 50 1 25 74 3 34 63
Proximal contact
94 4 2 82 16 2 91 7 1 85 13 2
Change of sensitivity
97
3 100
100
98
2
Hyper- 91 7 2 100
100
100
sensitivity
Radiographic assessment
91 4 5
96 1 3
Table 5.2: Descriptive statistics for all assessed restorations.
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years
65
Baseline (n=36) 2 Years (n=36) 4 Years (n=36) 6 Years (n=36)
Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo
[%] [%] [%] [%] Criterion
Surface roughness
100
97 3
92 8
78 22
Color match 92 8 92 8 81 14 5 78 22
Marginal integrity
50 47 3
53 47
36 64
39 61
Tooth integrity 86 14
47 42 11 31 58 11 33 50 17
Restoration integrity
100
11 45 44 3 28 69 3 39 58
Proximal contact
94 3 3 89 11 94 6 83 17 Change of sensitivity
100 100 100 100 Hyper-
97 3 100 100 100 sensitivity
Radiographic assessment
89 3 8 97 3
Table 5.3: Descriptive statistics for all Grandio restorations. *
Chapter 5
66
Baseline (n=32) 2 Years (n=32) 4 Years (n=32) 6 Years (n=32)
Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo Alpha1 Alpha2 Bravo
[%] [%] [%] [%]
Criterion
Surface roughness 100
100
94 6
87 13
Color match 97 3 94 6 88 13 91 9
Marginal integrity 37 63
69 31
31 69
44 56
Tooth integrity 97 3
31 53 16 28 53 19 28 47 25
Restoration integrity
85 9 6 6 38 56
22 78 3 28 69
Proximal contact 94 3 3 75 22 3 88 9 3 88 9 3
Change of sensitivity 94
6 100
100
97
3
Hyper- 84 13 3 100
100
100
sensitivity
Radiographic assessment 94 6
94 3 3
Table 5.4: Descriptive statistics for all Tetric Ceram restorations.
Criterion Baseline (n=68)
24 months (n=68)
48 months (n=68)
72 months (n=68)
Alpha I Excellent
44.1 % 0.0 % 0.0 % 0.0%
Alpha II Negative step 8.8 % 44.1 % 29.4% 38.2% Slight defects, easily Overhang 44.1 % 5.9 % 4.4% 1.5% correctable Stained
overhang 1.5 % 10.3 % 0.0 % 1.5%
Bravo Slight defects, not
Gap / negative step
1.5 % 16.2 % 23.5% 11.8%
correctable without damage
Staining 0.0 % 23.5 % 42.6% 47.2%
Table 5.5a: Descriptive statistics regarding “marginal integrity” (all restorations).
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years
67
Criterion Baseline (n=36)
24 months (n=36)
48 months (n=36)
72 months (n=36)
Alpha I Excellent
50.0 % 0.0 % 0.0% 0.0%
Alpha II Negative step 5.6 % 38.9 % 27.8% 33.3% Slight defects, easily
Overhang 38.9 % 2.8 % 8.3% 2.8%
correctable Stained overhang
2.8 % 11.1 % 0.0 % 2.8%
Bravo Slight defects,
Gap / negative step
2.8 % 19.4 % 25.0% 8.3%
not correctable without damage
Staining 0.0 % 27.8 % 38.9% 52.8%
Table 5.5b: Descriptive statistics regarding “marginal integrity” (Grandio restorations).
Criterion Baseline (n=32)
24 months (n=32)
48 months (n=32)
72 months (n=32)
Alpha I Excellent 37.5 % 0.0 % 0.0% 0.0%
Alpha II Negative step 12.5 % 50.0 % 31.3% 43.8% Slight defects, easily Overhang 50.0 % 9.4 % 0.0 % 0.0 %
correctable Stained overhang
9.4 % 0.0 % 0.0 %
Bravo Gap / negative step
0.0 % 12.5 % 21.9% 15.6%
Slight defects, not correctable without damage
Staining 0.0 % 18.8 % 46.9% 40.6%
Table 5.5c: Descriptive statistics regarding “marginal integrity” (Tetric Ceram restorations).
Chapter 5
68
Criterion Baseline (n=68)
24 months (n=68)
48 months (n=68)
72 months (n=68)
Alpha I Excellent 91.2 % 39.7 % 29.4% 30.9%
Alpha II Enamel chipping
1.5 % 4.4 % 0.0 % 5.9 %
Slight defects, easily
Enamel crack 7.4 % 42.6 % 55.9% 41.2%
correctable Wear 0.0 % 0.0 % 0.0 % 1.5 %
Bravo Enamel chipping
0.0 % 10.3 % 14.7% 13.2%
Slight defects, not correctable without damage
Enamel crack 0.0 % 2.9 % 0.0 % 5.9 %
Wear 1.5 %
Table 5.6a: Descriptive statistics regarding “tooth integrity” (all restorations).
Criterion Baseline (n=36)
24 months (n=36)
48 months (n=36)
72 months (n=36)
Alpha I Excellent 86.1 % 47.2 % 30.6% 33.3%
Alpha II Enamel chipping
2.8 % 2.8 % 0.0 % 5.6 %
Slight defects, easily
Enamel crack
11.1 % 38.9 % 58.3% 41.7%
correctable Wear 0.0 % 0.0 % 0.0 % 2.8 %
Bravo Enamel chipping
0.0 % 8.3 % 11.1% 8.3 %
Slight defects, not correctable without damage
Enamel crack
0.0 % 2.8 % 0.0 % 5.6 %
Wear 0.0 % 0.0 % 0.0 % 2.8 %
Table 5.6b: Descriptive statistics regarding “tooth integrity” (Grandio restorations).
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years
69
Criterion Baseline (n=32)
24 months (n=32)
48 months (n=32)
72 months (n=32)
Alpha I Excellent 96.9 % 31.3 % 28.1% 28.1%
Alpha II Enamel chipping
0.0 % 6.3 % 0.0 % 6.3 %
Slight defects, easily
Enamel crack
3.1 % 46.9 % 53.1% 40.6%
correctable
Bravo Enamel chipping
0.0 % 12.5 % 18.8% 18.8%
Slight defects, not correctable without damage
Enamel crack
0.0 % 3.1 % 0.0 % 6.3 %
Table 5.6c: Descriptive statistics regarding “tooth integrity” (Tetric Ceram restorations).
Criterion
Baseline (n=68)
24 months (n=68)
48 months (n=68)
72 months (n=68)
Alpha I Excellent 92.6 % 8.8 % 1.5% 2.9%
Alpha II Chipping 2.9 % 0.0 % 0.0% 1.5% Slight defects, easily
Crack 0.0 % 1.5 % 0.0% 0.0%
correctable Roughness / Abrasion
1.5 % 39.7 % 25.0% 32.4%
Bravo Chipping 0.0 % 2.9 % 7.4% 2.9% Slight defects, not correctable without damage
Crack probing 2.9 % 0.0 % 4.4% 1.5%
Abrasion 0.0 % 30.9 % 51.5% 58.8% Roughness 0.0 % 4.4 % 7.4% 0.0% Void 0.0 % 11.8 % 2.9% 0.0%
Table 5.7a: Descriptive statistics regarding “restoration integrity” (all restorations).
Chapter 5
70
Criterion Baseline (n=36)
24 months (n=36)
48 months (n=36)
72 months (n=36)
Alpha I Excellent 100.0 % 11.1 % 2.8% 2.8%
Alpha II Chipping 0.0 % 0.0 % 0.0 % 0.0 % Slight defects, easily
Crack 0.0 % 0.0 % 0.0 % 0.0 %
correctable Roughness / Abrasion
0.0 % 44.4 % 27.8% 38.9%
Bravo Chipping 0.0 % 5.6 % 8.3% 2.8% Slight defects, not correctable without damage
Crack probing 0.0 % 0.0 % 2.8% 0.0 %
Abrasion 0.0 % 16.7 % 50.0% 55.6% Roughness 0.0 % 5.6 % 8.3% 0.0 % Void 0.0 % 16.7 % 0.0% 0.0 %
Table 5.7b: Descriptive statistics regarding “restoration integrity” (Grandio restorations).
Criterion Baseline (n=32)
24 months (n=32)
48 months (n=32)
72 months (n=32)
Alpha I Excellent
84.4 % 6.3 % 0.0 % 3.1 %
Alpha II Chipping 6.3 % 0.0 % 0.0 % 3.1 % Slight defects, easily
Crack 0.0 % 3.1 % 0.0 % 0.0 %
correctable Roughness / Abrasion
3.1 % 34.4 % 21.9% 25.0%
Bravo Chipping 0.0 % 0.0 % 6.3% 3.1% Slight defects, not correctable without damage
Crack probing 6.3 % 0.0 % 6.3% 3.1%
Abrasion 0.0 % 46.9 % 53.1% 62.5% Roughness 0.0 % 3.1 % 6.3% 0.0 % Void 0.0 % 6.3 % 6.3% 0.0 %
Table 5.7c: Descriptive statistics regarding “restoration integrity” (Tetric Ceram
restorations).
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years
71
48 months 72 months
Criterion premolars (n=45)
molars (n=23)
premolars (n=45)
molars (n=23)
Alpha I Excellent
2.2 % 4.3 % 0.0 % 0.0 %
Alpha II Negative step
40.0% 8.7 % 44.4% 26.1 %
Slight defects, easily Overhang 6.7 % 0.0 % 2.2 % 0.0 % correctable Stained
overhang 0.0 % 0.0 % 2.2% 0.0%
Bravo Gap /
negative step
20.0% 26.1 % 8.9 % 17.4%
Slight defects, not correctable without damage
Staining 31.1% 60.9 % 42.2% 56.5%
Table 5.8a: Descriptive statistics of premolars vs. molars regarding “marginal integrity”. No significant difference could be calculated after 72 months (p=0.073) in contrast to the result after 48 months (p=0.007; Mann‐Whitney U‐test).
48 months 72 months
Criterion premolars (n=45)
molars (n=23)
premolars (n=45)
molars (n=23)
Alpha I Excellent
37.8 % 13.0 % 42.2% 8.7 %
Alpha II Enamel chipping
0.0 % 0.0 % 6.7 % 13.0 %
Slight defects, easily Enamel crack
53.3% 60.9 % 35.6% 52.2 %
correctable Wear 0.0 % 0.0 % 2.2% 0.0 %
Bravo Enamel chipping
8.9 % 26.1 % 6.7 % 26.1 %
Slight defects, not correctable without damage
Enamel crack
0.0 % 0.0 % 4.4 % 8.7 %
Wear 0.0 % 0.0 % 2.2 % 0.0 % Table 5.8b: Descriptive statistics of premolars vs. molars regarding “tooth integrity”. Significant differences could be calculated after 48 (p=0.013) and 72 months (p=0.003; Mann‐Whitney U‐test).
Chapter 5
72
48 months 72 months
Criterion premolars (n=45)
molars (n=23)
premolars (n=45)
molars (n=23)
Alpha I Excellent
2.2 % 4.3 % 0.0 % 8.7 %
Alpha II Chipping 2.2 % 0.0 % 2.2 % 0.0 % Slight defects, easily
Crack 0.0 % 0.0 % 0.0 % 0.0 %
correctable Roughness / Abrasion
33.3 % 4.3 % 40.0% 17.3%
Bravo Chipping 4.4 % 8.7 % 4.4 % 0.0 % Slight defects, not correctable without damage
Crack probing
4.4 % 4.3 % 2.2 % 0.0 %
Abrasion 40.0 % 73.9 % 51.1 % 73.9% Roughness 8.9 % 4.3 % 0.0 % 0.0 % Void 4.4 % 0.0 % 0.0 % 0.0 %
Table 5.8c: Descriptive statistics of premolars vs. molars regarding “restoration integrity”. No significant difference was calculated after 72 months (p=0.321) in contrast to the 48 month findings (p=0.018; Mann‐Whitney U‐test).
Tooth integrity significantly deteriorated due to increasing enamel cracks over time
(p<0.05; Table 5.6). Enamel chippings or cracks were significantly more frequently
observed in molars (26% bravo after 4 years / 35 % bravo after 6 years) than in
premolars (9% bravo after 4 years/11% bravo after 6 years). The main reasons for
decreasing “restoration integrity” were visible signs of surface roughness and distinct
wear traces (28% after 1 year, 75% after 2 years, 84% after 4 years, 91% after 6
years; Table 5.7). Visible wear of both materials under investigation was detectable
earlier in molars (74% bravo after 4 years) than in premolars (40% bravo after 4
years; Table 5.8c, Figures 5.1 and 5.2).
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years
73
Figure 5.1
Clinical view of a Grandio restoration after 6 years (upper left first premolar). A discoloration at the palatal proximal margin was detectable, probably due to a small overhang. Wear and negative step formation in the occlusal portion of the restoration was obvious. The surface appears rough.
Figure 5.2
Clinical view of a Tetric Ceram restoration after 6 years (upper right first premolar, same patient as in Figure 5.1). No discoloration was detectable clinically. Wear and negative step formation in the occlusal portion of the restoration was detectable. In the occlusal contact area of the lateral ridge, the surface show signs of surface fatigue (small cracks) and the surface appears rough.
Discussion
Fundamental prerequisites for clinical success with resin-based composites as
posterior restorative material still must be met in order to achieve clinical success
with this particular group of dental materials.10-12,18,30,41 There is no doubt that resin
composites are almost perfect for minimally invasive posterior cavities, however, it
is to the date not fully understood how far we can go in terms of cavity extension. So
it is still frequently argued that resin composites suffer some disadvantages in very
Chapter 5
74
extended cavities and should therefore be replaced by other materials and techniques
such as indirectly bonded restorations.21 When large cavities need to be restored, the
major objections against resin composites are the dangers of developing recurrent
caries and the non-predictable wear rates over time.42 The problem with secondary
caries is even more common when proximal Class II margins are located in dentin.
At least from in vitro and in vivo investigations dealing with indirect ceramic inlays
and onlays, it is proven that even margins extending beyond the amelocemental
junction can be safely restored.6,16,25,42 For Class V restorations it is similar, although
50% of margin length is located in dentin.4,19,20,22 On the other hand, proximal
marginal seal in dentin-bordered cavities restored with direct resin composite
restorations, is underrepresented in the literature of the field.21 Thus, the setup of this
clinical trial excluded minimally invasive cavities and was mainly restricted to
amalgam replacement restorations resulting in 35% of cavities with no proximal-
cervical enamel and 49% with <0.5 mm proximal enamel width. Finally, after 6
years of clinical service, these restorations did not reveal significantly worse clinical
outcomes, and moreover, neither recurrent caries nor severe marginal staining was
detected.
The most recent recommendations for clinical trials with restorative materials 31
could not be addressed, because these recommendations were published considerably
after the beginning of the present study. Therefore, it was not possible to include
more evaluation aspects among well-suited protocols such as the CONSORT
statement.15,16,40,42
Direct and indirect resin composites as well as all-ceramic inlays have to be bonded
for acceptable clinical outcome.5,10,11,14,30 The selection of materials for this study
was carried out after thorough in vitro testing with promising results for both
materials used, in terms of good marginal adaptation and long-term stability,24,27,28,43
because previous studies clearly indicated that it may be dangerous to make clinical
trials with materials having failed some preclinical screenings.15,43
Although the different adhesives used in the present investigation required special
bonding protocols, i.e. wet bonding with the acetone-based Solobond M, this
obviously did not negatively influence clinical results in terms of postoperative
hypersensitivities. Initially, restorations bonded with Syntac exhibited slightly more
hypersensitivities (baseline to 6 months) (3% vs. 0% bravo scores), but this played
Microhybrid vs. nanohybrid resin composites in extended cavities after 6 years
75
no role past the 1-year recall. Therefore, both the internal sealing of dentin and tight
dentin margins were possible with both adhesives under investigation. Even so,
dealing with the clinical outcome of complete restorative systems (i.e. adhesive plus
resin composite) always is more complicated than evaluating two adhesives with one
resin composite in order to minimize variables. This paper is not able to completely
elucidate this particular problem, but the promising results over the 6-year period
support the assumption that both systems are clinically acceptable.
Including nanofillers in recent resin composites is widespread in adhesive dentistry
today. Major advantages are primarily enhanced translucency effects and increased
polishability.12,44,45 Irrespective of these aspects, clinical reports dealing with this
class of materials exhibited no significant advantages in vivo.12 In the present
investigation, Tetric Ceram was used as fine hybrid resin composite (without
nanofillers), and Grandio was used as one of the first resin composites with
incorporated nanofillers among conventional hybrid type fillers as so-called
nanohybrid resin composite.12,32,37
Altogether, the null hypothesis of the present investigation was confirmed because
there was no difference in the clinical behavior between Grandio and Tetric Ceram
used for extended Class II posterior restorations.
Chapter 5
76
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5. Bergenholtz G. Evidence for bacterial causation of adverse pulpal responses in
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7. Manhart J, Chen HY, Hickel R. Three-year results of a randomized controlled
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8. Peumans M, Kanumilli P, De Munck J, Van Landuyt K, Lambrechts P, Van
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composite restorations placed using the total-etch technique. J Esthet Restor
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12. Ernst CP, Brandenbusch M, Meyer G, Canbek K, Gottschalk F, Willershausen
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13. Feilzer AJ, de Gee AJ, Davidson CL. Setting stress in composite resin in
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15. Krämer N, Garcia-Godoy F, Frankenberger R. Evaluation of resin composite
materials. Part II: in vivo investigations. Am J Dent 2005; 18:75-81.
16. Krämer N, Taschner M, Lohbauer U, Petschelt A, Frankenberger R. Totally
bonded ceramic inlays and onlays after eight years. J Adhes Dent 2008;
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17. Frankenberger R, Perdigao J, Rosa BT, Lopes M. "No-bottle" vs "multi-bottle"
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19. Van Meerbeek B, Perdigao J, Lambrechts P, Vanherle G. The clinical
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22. Van Meerbeek B, Kanumilli P, De Munck J, Van Landuyt K, Lambrechts P,
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of enamel. Dent Mater 2005; 21:375-383.
23. De Munck J, Van Meerbeek B, Yoshida Y et al. Four-year water degradation
of total-etch adhesives bonded to dentin. J Dent Res 2003; 82:136-140.
24. Frankenberger R, Tay FR. Self-etch vs etch-and-rinse adhesives: effect of
thermo-mechanical fatigue loading on marginal quality of bonded resin
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25. Frankenberger R, Krämer N, Lohbauer U, Nikolaenko SA, Reich SM.
Marginal integrity: is the clinical performance of bonded restorations
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26. Dietschi D, De Siebenthal G, Neveu-Rosenstand L, Holz J. Influence of the
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27. Frankenberger R, Strobel WO, Krämer N et al. Evaluation of the fatigue
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28. Frankenberger R, Strobel WO, Lohbauer U, Krämer N, Petschelt A. The effect
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Biomed Mater Res B Appl Biomater 2004; 69:25-32.
29. Frankenberger R, Krämer N, Petschelt A. Technique sensitivity of dentin
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adaptation. Oper Dent 2000; 25:324-330.
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evaluation of a nanofilled composite in posterior teeth: 12-month results. Oper
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31. Hickel R, Roulet JF, Bayne S et al. Recommendations for conducting
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controlled clinical studies of dental restorative materials. Science Committee
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for evaluation (Part II) of direct and indirect restorations including onlays and
partial crowns. J Adhes Dent 2007; 9 Suppl 1:121-147.
32. Lambrechts P, Braem M, Vanherle G. Buonocore memorial lecture. Evaluation
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33. Lohbauer U, Frankenberger R, Krämer N, Petschelt A. Strength and fatigue
performance versus filler fraction of different types of direct dental
restoratives. J Biomed Mater Res B Appl Biomater 2006; 76:114-120.
34. Clelland NL, Pagnotto MP, Kerby RE, Seghi RR. Relative wear of flowable
and highly filled composite. J Prosthet Dent 2005; 93:153-157.
35. Schwartz JI, Söderholm KJ. Effects of filler size, water, and alcohol on
hardness and laboratory wear of dental composites. Acta Odontol Scand 2004;
62:102-106.
36. Turssi CP, De Moraes PB, Serra MC. Wear of dental resin composites: insights
into underlying processes and assessment methods--a review. J Biomed Mater
Res B Appl Biomater 2003; 65:280-285.
37. Ferracane JL, Condon JR. In vitro evaluation of the marginal degradation of
dental composites under simulated occlusal loading. Dent Mater 1999; 15:262-
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38. Palaniappan S, Elsen L, Lijnen I, Peumans M, Van Meerbeek B, Lambrechts P.
Three-year randomised clinical trial to evaluate the clinical performance,
quantitative and qualitative wear patterns of hybrid composite restorations.
Clin Oral Investig 2010;14:441-458.
39. Palaniappan S, Bharadwaj D, Mattar DL, Peumans M, Van Meerbeek B,
Lambrechts P. Three-year randomized clinical trial to evaluate the clinical
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40. Needleman I, Worthington H, Moher D, Schulz K, Altman DG. Improving the
completeness and transparency of reports of randomized trials in oral health:
the CONSORT statement. Am J Dent 2008; 21:7-12.
41. Abdalla AI, Davidson CL. Comparison of the marginal integrity of in vivo and
in vitro Class II composite restorations. J Dent 1993; 21:158-162.
42. Krämer N, Garcia-Godoy F, Reinelt C, Frankenberger R. Clinical performance
of posterior compomer restorations over 4 years. Am J Dent 2006; 19:61-66.
43. Frankenberger R, Garcia-Godoy F, Lohbauer U, Petschelt A, Krämer N.
Evaluation of resin composite materials. Part I: in vitro investigations. Am J
Dent 2005; 18:23-27.
44. Attar N. The effect of finishing and polishing procedures on the surface
roughness of composite resin materials. J Contemp Dent Pract 2007; 8:27-35.
45. Jung M, Sehr K, Klimek J. Surface texture of four nanofilled and one hybrid
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81
CHAPTER 6
General discussion:
Is the clinical performance of bonded restoratives predictable in the laboratory?
Chapter 6
82
Introduction
Dental biomaterials are subjected to considerable degradation processes during
clinical service over time.1-5 After amalgam, having been the standard restorative for
posterior restorations for more almost two centuries, today tooth-colored materials
such as resin-based composites are the treatment option of choice for the majority of
patients.6-13 Adhesive dentistry's long-term success is proven for pit and fissure
sealing, direct and indirect resin composites, and ceramic inlays.11,13-25 Nevertheless,
even in the era of nano-optimized resin-based composites, polymerization shrinkage
still relies on durable adhesion to enamel and dentin as a fundamental prerequisite, and
vice versa, without successful adhesion, gap formation potentially jeopardizes clinical
long-term success.4,26-36
Adhesion to phosphoric acid etched enamel is no longer a concern for dentists due to
its clinically proven durability,4-6,31,35,37-40 however, durability of self-etch adhesives in
heavily loaded Classes I and II is still not clinically proven, whereas in cervical
lesions, medium-term results are promising.12,21,22,41,42 Knowledge about adhesion to
dentin is different; the self-etch approach - at least with two steps - seems to be the
most promising way to get durable bonds beside multi-step etch-and-rinse
systems.30,31,35,40,43,44 Comparing enamel and dentin as adhesive substrates still reveals
dentin to be the weaker substrate due its tubular structure and intrinsic wetness which
leads to permeability problems with all-in-one self-etch adhesives.27,31,33-35,44-47
More or less all degradation processes found for dental biomaterials are related to
fatigue.10,37,48-55 Especially with resin-based composites, fatigue is not only a matter of
loss of adhesive performance over time (adhesive fatigue) but also of bulk fatigue
(fracture) and surface fatigue (wear). For resin composites, two fatigue phenomena
(adhesive fatigue leading to recurrent caries and bulk fatigue leading to fractures) are
responsible for the vast majority of clinical failures observed during clinical long-term
trials.6,7,11,16,56 Wear is in most of the cases less clinically relevant because worn resin
composites may still be clinically serviceable, however, loss of anatomic form over
time may lead to occlusal interferences.10,57-59 Research in restorative dentistry is,
since decades, focused on predicting clinical issues in the lab.60 Of course, clinical
long-term trials remain the ultimate instrument for thoroughly evaluating dental
biomaterials. However, the main problem with clinical trials is that when they give
General discussion
83
valuable results after several years of observation time, the adhesive and/or resin
composite may no longer be on the market.
Therefore, preclinical in vitro investigations are very important, however, it is
contradictorily reported in the literature whether these tests are able to reliably predict
clinical behavior. So the aim of this paper was to investigate this particular question
with a special focus on marginal integrity, bulk fatigue (fracture), and surface fatigue
(wear).
Materials and Methods
Publications in dental and biomaterial journals with dental materials since 1990 were
retrieved in PubMed, MedLine, Dimdi, and Embase. Search key words were: margin,
gap, marginal integrity, marginal adaptation, enamel margin, dentin margin, marginal
quality, fracture, chipping, bulk fracture, abrasion, and wear. We only chose papers
dealing with resin composites. Congress abstracts were completely ignored. Top
cited papers were retrieved from www.scopus.com in order to prioritize publications
that were frequently referred to39. As indicator for top cited papers, the frequency of
citations per year (CPA) was set >5.
Results
An overview of top cited papers dealing with marginal integrity, fatigue, and wear of
bonded restorations is displayed in Tables 6.1-6.3.
Marginal quality
Papers reporting direct comparisons between in vitro and in vivo results are scarce in
the literature in the field of adhesive dentistry. However, several evaluations of
marginal integrity from the preclinical point of view exist as do a few papers
focusing on marginal adaptation in vivo. Marginal integrity papers in vitro repeatedly
report a superior performance of etch-and-rinse adhesives in enamel
bonding,16,18,19,22,31,35,36,39,40,48,61,62 however, again there are contradictory reports of
Hannig et al. claiming self-etch adhesives being an alternative to phosphoric acid
even in stress-bearing cavities.63,64 For dentin bonding, Frankenberger and Tay
Chapter 6
84
reported equal results for etch-and-rinse adhesives and two-step self-etch adhesives
in dentin margins of Class II cavities after thermomechanical loading, and
significantly worse results when all-in-one adhesives were used for bonding of resin
composites in vitro.35
Abdalla and Davidson directly compared in vitro and in vivo applied resin composite
restorations in Class II cavities with less microleakage in the laboratory.65 Two
papers of our group investigated the resin composites Ariston pHc and Solitaire both
in vitro and in vivo. In the in vitro part, both restoratives exhibited some
shortcomings,36 however, these previously reported materials properties led to
catastrophic outcomes in vitro with mean survival times for both materials of 2.4
years.66 Frankenberger et al. also compared the same materials in vitro and in vivo
with respect to marginal adaptation of Class I resin composite resotrations in
molars.39 Here, some minor differences were noticed between the in vitro and the in
vivo situation, however, the rankings regarding the adhesive’s performances were the
same, revealing superior results for etch-and-rinse adhesives when compared to self-
etch adhesives.39 And among the self-etch adhesives, two-step self-etch adhesives
were more effective than one-step self etch adhesives.39 Another publication
observed marginal quality for Grandio and Tetric Ceram restorations both in vitro
and in vivo over 6 years.4 Also here, in vitro and in vivo results for marginal quality
were similar until the 6-year recall with a combined 6-year water
storage/thermomechanical loading scenario.4 Heintze et al. compared results of
clinical studies with bonded Class V resin composite restorations with two different
in vitro stressing regimens for a variety of 37 adhesives.44 They concluded that the
systematic analysis of the correlation between laboratory data of marginal adaptation
and the outcome of clinical trials of Class V restorations revealed that the correlation
was weak and only present if studies were compared which used the same composite
for the in vitro and in vivo evaluation.44
Bulk fatigue / fracture behavior
Regarding the fatigue behavior related to flexural strength, some studies evaluated the
flexural fatigue behavior in terms of a so-called flexural fatigue limit (FFL).48,49,67-79
The flexural fatigue limits (FFL) of the composite materials were determined for 105
General discussion
85
cycles under equivalent test conditions at a frequency of 0.5 Hz (n = 25). The
“staircase” approach was used for fatigue evaluation.70 For every cycle the stress
alternated between 1 MPa and the maximum stress. Tests were conducted
sequentially, with the maximum applied stress in each succeeding test being increased
or decreased by a fixed increment of stress, according to whether the previous test
resulted in failure or not. The first specimen was tested at approximately 50% of the
initial flexural strength value. As the data are cumulated around the mean stress, the
number of specimens required is less than with other methods. The mean flexural
fatigue limit (FFL) is determined using Eq. 1 and standard deviation, using Eq. 2,
respectively:
5.00
i
i
n
indXFFL (1)
029.062.1
2
22
i
iii
n
innindSD (2)
X0 is the lowest stress level considered in the analysis and d is the fixed stress
increment. To determine the FFL, the analysis of the data was based on the least
frequent event (failures versus nonfailures). In Eq. 1 a negative sign was used when
the analysis was based on failures. The lowest stress level considered was designated
as i = 0, the next as i = 1, and so on, and ni was the number of failures or non-failures
at the given stress level. Turssi et al. evaluated FFLs of microfill versus nanfilled resin
composite with equal to worse outcome for the nanomaterials.80 Abe et al. compared
an array of resin composites with results having been inferior for most of the packable
resin composites under investigation.81 Lohbauer et al. evaluated the FFL behavior of
different resin composites for posterior use and concluded that high initial flexural
strengths do not automatically mean high FFLs.77,78 In a direct in vitro - in vivo
comparison of resin-based materials regarding FFL and clinical outcome, the low FFL
for the resin composite Solitaire led to unacceptably high fracture rates in vivo, so the
authors concluded that FFL >30 MPa is the critical threshold value for bulk fatigue in
order to withstand masticatory forces and clinical fatigue life over time.66,77,78
Chapter 6
86
Surface contact fatigue/clinical wear
Early abrasion studies during the first stages of resin composite testing were cast
analyses according to some scales such as the Leinfelder scale allowing estimates of
clinical wear in terms of calibrated casts in 50 µm steps.1,52,53,82-88 Compared to
preclinical screenings where normally only the test material is abraded,54,55,89,90
clinical wear measurements in restorative dentistry always deal with enamel and
restorative materials and an exact determination of reference points is only possible
with demanding 3D laser devices.57-59,91-93 Due to the expensive tool and
sophisticated software issues, very few 3D laser scan studies dealing with clinical
wear phenomena are available in the literature, reporting wear rates after 3 years of
clinical service of ~80 µm.91,92
Discussion
In vitro research on dental adhesive biomaterials is necessary, because a) special
experimental research questions would never pass an ethics committee and b) not
every adhesive and/or resin-based composite can be the subject of randomized
prospective clinical trials because these are time-consuming and expensive.
Nevertheless, it is still not fully understood whether and what we can really simulate
in the lab and where major shortcomings are. So, the objective of this paper was to
clarify the question “Is clinical performance of dental biomaterials predictable in the
lab?”. Roulet thought about this topic years ago indicating that in vitro research
suffers from interpretation problems and even in vivo studies always reveal
significant limitations.94
Today, there are still only a handful of studies directly comparing in vitro with in
vivo results from the same workgroup. Abdalla and Davidson published the first
“Comparison of the marginal integrity of in vitro and in vivo Class II composite
restorations” being unique so far. This investigation dealt with microleakage in
laboratory and ex vivo specimens.65 Whereas only 40% of in vitro specimens
revealed microleakage after mechanical loading, 100% of in vivo restorations
exhibited microleakage.65 Therefore, the authors concluded that laboratory studies
may not be able to completely predict clinical behavior of adhesive junctions in the
oral cavity.65
General discussion
87
Clinical studies are mainly peformed in Classes V or II cavities being the latter the
most difficult to obtain. Major advantages of clinical trials in Class V cavities were
referred to as non-existing macromechanical retention, considerable amounts of
dentin margins, probably less influence of the particular resin composite, and easy
judgement of retention vs. retention loss.20-22,43,44,62 However, the main problem in
adhesive dentistry is not retention of Class V restorations, it is still to prove whether
bonded resin compositess are able to fully replace amalgam in stress-bearing
posterior cavities. However, disadvantages of Classes I and II are that retention is
often provided by undermining dentin decay and subsequent undercuts, and less
presence of clinically judgeable dentin margins.4,6,9 So marginal quality assessments
in posteror stress-bearing resin composite restorations may be less suitable to
investigate adhesives alone compared to non-carious Class V restorations, however,
clinical importance facing millions of stress-bearing posterior resin composite
restorations is great.6
Opdam et al. reported marginal integrity and postoperative sensitivity in Class II
restorations in vivo finding that etch-and-rinse adhesives showed good results in
enamel bonding and self-etch adhesives produced less postoperative
hypersensitivity.17 When clinical staining is related to inferior or loss of enamel
bonding durability, and postoperative hypersensitivities are linked to inferior or loss
of dentin bonding quality, this was predictable from laboratory investigations.39
Four recent publications of our workgroup aimed to evaluate resin composites and
their corresponding adhesives in both aspects, in vitro and in vivo.4,36,39,66
Frankenberger et al. reported in vitro performance of resin composites by means of
microtensile bond strenghts to enamel and dentin, flexural fatigue behavior, and wear
behavior. The resin composites Ariston pHc and Solitaire were different from
contemporary resin composites, i.e. Ariston exhibited significantly less adhesion,
Solitaire revealed an inferior flexural fatigue limit.36 Krämer et al. reported clinical
findings of identical materials demonstrating catastrophic clinical outcome with
several bulk fractures of Solitaire, and even more failures of Ariston restorations
caused by postoperative hypersensitivities and enamel fractures.66 Frankenberger et al.
compared different classes of adhesives in vitro and in vivo with identical enamel
bonding rankings for the different bonding approaches.39 The same was true for a
recent publication showing 6-year results in vitro and in vivo with again similar
Chapter 6
88
outcomes over time.4 So in all cases, clinical performance of resin composites in
Classes I and II cavities was predictable from laboratory results, especially significant
differences between etch-and-rinse adhesives and self-etch adhesives in enamel
bonding durability. So even the results of Heintze et al.43,44 actually match the
outcome of our workgroup where always the same resin composites were used in vitro
and in vivo which may have contributed to the more consistent values.4,39
All these findings clearly reflect that marginal quality prediction is possible from
laboratory studies, however, marginal integrity is only one among several crucial
factors for clinical outcome with bonded tooth-colored materials. A high amount of
gaps after thermomechanical challenge in vitro increases the probability of the same
scenario in vivo. However, this does not necessarily lead to recurrent decay because
the presence of marginal gaps in vivo does not necessarily lead to secondary caries.
One ultimate question is still unclear: when e.g. resin composite restoration achieves
good results in an in vitro marginal quality assessment, it is rather predicable that its
clinical marginal quality will not cause significant problems. On the other hand, can
we conclude this also from the other side of the scale? Probably not. We still do not
know below which percentage of gap-free margin it is not safe to use the material
combination also clinically.
The final reason in favor of in vitro research regarding marginal quality is that many
studies focus on experimental questions that would never pass an ethics committee
for a clinical trial. In these cases in vitro studies are the only way, giving important
tendencies for clinical application of dental biomaterials. Among all in vitro
approaches to predict clinical outcome, thermomechanical loading and subsequent
marginal analysis is the closest scenario to the clinical situation, however, it is almost
as intricate as a clinical trial.
As the frequency of citations as well as the presence of top cited papers clearly
reflects, flexural fatigue behavior of dental biomaterials receives far less attention.
However, a few top papers indicate that flexural fatigue behavior of dental
biomaterials is closely related to clinical outcome in terms of fracture
behavior.36,48,49,66,67,70,71,95 Compared to the multiple questions about marginal quality,
FFL measurements in vitro are able to exactly define a kind of lower borderline at
~30 MPa flexural fatigue limit, because below that level clinically much more
fractures were observed.66 On the other hand, there are still not enough clinical data
General discussion
89
proving that higher and higher initial and fatigue values for flexural strength
automatically lead to less fractures observed in clinical recalls after several years of
clinical service.96
Wear is an important consequence of occlusal interactions.10,16,91,97,98 If not
controlled, wear could lead to poor masticatory function with a concomitant
reduction in quality of life.99-102 However, for most of the investigated resin-based
composites this is simply not the case.10,16,91,97,98 Compared with other modes of in
vitro testing of dental biomaterials, preclinical wear simulation is the most
sophisticated branch.52,53,86,98,103,104 Clinical wear is a very complex scenario being
influenced by several factors such as pH, contact-free abrasion, occlusal contact
fatigue, and antagonist structure and material.52,53,86,98,103,104 Most of the in vitro
regimens are only able to mimic one of these several co-factors. Analyzed as an
array, many different wear simulation scenarios could finally result in an appropriate
estimation of clinical wear.52,53,86,98,103,104 Also here it is clearly visible in Table 6.3
that the scientific importance of wear investigations decreased during the last decade
and top cited papers are scarce. 3D laserscans are the ultimate instrument to evaluate
clinical wear, however, there is an urgent need for more clinical data with different
restoratives.98
In times of ranking publications according to their journal impact factor (JIF),
citations are an important tool in order to judge the importance of individual papers
in the literarure. High JIF regularly result from frequently cited papers. As performed
before with a substantial amount of citations, the authors again decided to include
this aspect by focussing on frequently cited papers being indicated by CPA (citations
per anno; Tables 6.1-6.3). For the top cited paper published by Van Meerbeek et al.
this means that this single publication receives an individual or "true" impact factor
of 50 compared to the journal impact factor of ~3 meaning that the importance of the
paper exceeds the importance of the journal by means of 16. Although citation
rankings and measurement are always criticized to be somewhat subjective, it is the
only way to judge or rank scientific outcome. The same is true for the journal impact
factor, i.e. it may not be an optimum tool for author evaluations, however, is there a
better alternative? So finally, the inclusion of top cited papers is of at least some
relevance and should not be underestimated.
Chapter 6
90
Conclusions
Clinical marginal quality is predictable from in vitro adhesive fatigue investigations
with thermomechanical loading, but it is not possible to determine a cut off for
clinically successful marginal quality. Flexural fatigue can be appropriately
determined in the lab as well, having been successful in defining lower borderlines for
additional clinical safety. To compare in vitro and in vivo results according to wear
phenomena, valid in vivo results are too seldom. Altogether, it has to be taken into
account that the described co-factors are only a few among several important aspects
in restorative dentistry, i.e. overall clinical performance is not predictable from fatigue
aspects alone.
Year Author Title Citations per year (CPA)
2003 Van Meerbeek et al.13 Adhesion to enamel and dentin: Current status and future challenges
50.9
1997 Mehl at al.23 Physical properties and gap formation of light-cured composites with and without softstart polymerization
14.5
1995 Feilzer et al.24 Influence of light intensity on polymerization shrinkage and integrity of restoration-cavity interface
12.1
2005 Frankenberger & Tay35
Self-etch vs etch-and-rinse adhesives: effect of thermo-mechanical fatigue loading on marginal quality of bonded resin composite restorations
10.8
1990 Kemp-Scholte et al.41 Complete marginal seal of Class V resin composite restorations effected by increased flexibility
10.3
1999 Hannig et al.63 Self-etching primer vs. phosphoric acid: an alternative concept for composite-to-enamel bonding
10.0
2000 Peumans et al. 25 Porcelain veneers: A review of the literature 9.0 2000 Frankenberger et al.45 Technique sensitivity of dentin bonding: Effect of
application mistakes on bond strength and marginal adaptation
8.6
1998 Opdam et al.17 Marginal integrity and postoperative hypersensitivity in Class II resin composite restorations in vivo
6.8
2007 Heintze43 Systematic reviews: I. The correlation between laboratory tests on marginal quality and bond strength. II. The correlation between marginal quality and clinical outcome
6.0
2000 Frankenberger et al.2 Leucite-reinforced glass ceramic inlays and onlays after six years: clinical behavior
6.0
1990 Kemp-Scholte & Davidson60
Marginal integrity related to bond strength and strain capacity of composite resin restorative systems
5.8
2007 Frankenberger et al. 39
Marginal integrity: Is the clinical performance of bonded restorations predictable in vitro?
5.7
Table 6.1: Top cited papers (CPA >5) regarding marginal adaptation of resin composites.
General discussion
91
Year Author Title Citations per year (CPA)
1997 Gladys et al.95 Comparative physico-mechanical characterization of new hybrid restorative materials with conventional glass-ionomer and resin composite restorative materials
11.4
2003 Drummond et al.73 Static and cyclic loading of fiber-reinforced dental resin
8.9
2005 Lohbauer et al.78 The effect of different light-curing units on fatigue behavior and degree of conversion of a resin composite
5.6
Table 6.2: Top cited papers (CPA >5) regarding bulk fatigue behavior of resin composites.
Year Author Title Citations per year (CPA)
1998 Bayne et al.99 A characterization of first-generation flowable composites
11.3
2005 Sarrett et al.101 Clinical challenges and the relevance of materials testing for posterior composite restorations
9.6
1996 Mair et al.100 Wear: Mechanisms, manifestations and measurement. Report of a workshop
7.4
2005 Turssi et al.102 Filler features and their effects on wear and degree of conversion of particulate dental resin composites
7.4
Table 6.3: Top cited papers (CPA >5) regarding surface fatigue / wear of resin composites.
Chapter 6
92
Figure 6.1: Biodegradation of a resin composite restoration in a lower first molar after 6 years of clinical service. R: Resin composite. E: Enamel. Clinical wear is clearly visible around the occulsal margins. Gap formation does not play a major role in this case.4
General discussion
93
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91. Palaniappan S, Bharadwaj D, Mattar DL, Peumans M, Van Meerbeek B,
Lambrechts P. Three-year randomized clinical trial to evaluate the clinical
performance and wear of a nanocomposite versus a hybrid composite. Dent
Mater 2009;25:1302-1314.
92. Palaniappan S, Elsen L, Lijnen I, Peumans M, Van Meerbeek B, Lambrechts P.
Three-year randomised clinical trial to evaluate the clinical performance,
quantitative and qualitative wear patterns of hybrid composite restorations.
Clin Oral Investig 2010;14:441-458.
Chapter 6
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93. Winkler MM, Lautenschlager EP, Boghosian A, Greener EH. An accurate and
simple method for the measurement of dental composite wear. J Oral Rehabil
1996;23:486-493.
94. Roulet JF. Marginal integrity: clinical significance. J Dent 1994;22 Suppl 1:S9-
12.
95. Gladys S, Van Meerbeek B, Braem M, Lambrechts P, Vanherle G.
Comparative physico-mechanical characterization of new hybrid restorative
materials with conventional glass-ionomer and resin composite restorative
materials. J Dent Res 1997;76:883-894.
96. Lambrechts P, Ameye C, Vanherle G. Conventional and microfilled composite
resins. Part II. Chip fractures. J Prosthet Dent 1982;48:527-538.
97. Sarrett DC, Ray S. The effect of water on polymer matrix and composite wear.
Dent Mater 1994;10:5-10.
98. Turssi CP, De Moraes PB, Serra MC. Wear of dental resin composites: insights
into underlying processes and assessment methods--a review. J Biomed Mater
Res B Appl Biomater 2003;65:280-285.
99. Bayne SC, Thompson JY, Swift EJ, Jr., Stamatiades P, Wilkerson M. A
characterization of first-generation flowable composites. J Am Dent Assoc
1998;129:567-577.
100. Mair LH, Stolarski TA, Vowles RW, Lloyd CH. Wear: mechanisms,
manifestations and measurement. Report of a workshop. J Dent 1996;24:141-
148.
101. Sarrett DC. Clinical challenges and the relevance of materials testing for
posterior composite restorations. Dent Mater 2005;21:9-20.
102. Turssi CP, Ferracane JL, Vogel K. Filler features and their effects on wear and
degree of conversion of particulate dental resin composites. Biomaterials
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General discussion
103
103. Heintze SD, Cavalleri A, Forjanic M, Zellweger G, Rousson V. A comparison
of three different methods for the quantification of the in vitro wear of dental
materials. Dent Mater 2006;22:1051-1062.
104. Schwartz JI, Soderholm KJ. Effects of filler size, water, and alcohol on
hardness and laboratory wear of dental composites. Acta Odontol Scand
2004;62:102-106.
Chapter 6
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105
Summary
106
Tooth-colored materials such as resin composites should be safely used for patients in
terms of clinical behavior. Esthetics are more or less a side aspect in the posterior
region. However, it is probably the most important issue for patients all over the world
to receive invisible restorations. This summary section picks up relevant issues having
been addressed in the introduction section (Chapter 1) to build a thematic bridge in
this thesis and to provide some framework for future thoughts.
Resin composite materials are well-suited materials to bond to tooth hard tissues and
furthermore to support enamel and dentin in terms of cuspal adhesive stabilization. It
is well-proven that adhesion in dentistry can be safely applied in many ways, such as
pit and fissure sealings, direct and indirect resin composites, and bonded ceramic
restorations. Bonding to phosphoric acid etched enamel is accepted to be clinically
successful, however, marginal staining or gap formation have been also reported as
major incidents already after medium-term observations. Also dentin can be bonded
and sealed successfully, being rather quickly represented by the absence of
postoperative hypersensitivities. When no hypersensitivities occur, the dentin seal
should be estimated to be sufficient, at least to avoid fluid movement inside the dentin
tubules. Long-term bonding degradation over time is interesting to observe, therefore
it was the topic of the second part of the thesis to do so (Chapter 2). Also, the central
idea was to accelerate degradation in vitro, in this case degeneration of resin-dentin
bonds by artificial saliva compared to mineral oil (control). Resin-dentin beams
bonded with three different etch-and-rinse adhesives (two-step: Prime&Bond NT,
Excite/three-step: All-Bond 2) were prepared after 3 years of storage in the described
media and subjected to transmission electron microscopy (TEM). An "extreme
control" was introduced by autoclaving at 121°C and 103kPa. The TEM images
clearly showed that the extreme control scenario did not result in denatured collagen
when having been protected by adhesive resin. The control group with mineral oil
exhibited almost intact hybrid layers over 3 years with minimal silver deposits,
whereas in the test group with artificial saliva, extensive nanoleakage was observed.
All ultrastructural parameters, i.e. extent of nanoleakage, interfacial staining
characteristics, and the structure of the collagen fibrils in hybrid layers and underlying
dentin were completely different and revealed considerable aging processes when
storage was accelerated using artificial saliva.
Summary
107
Dentin bonding is more responsible for proper dentin seal and consequent reduction of
postoperative hypersensitivities. In contrast, enamel bonding is important for
restoration retention and marginal integrity, i.e. unstained margins, especially in the
visible area. Therefore, in the next stage marginal quality in enamel and dentin was
evaluated simultaneously in vitro and in vivo. This was achieved by starting both
investigations at the same time to get comparable results between preclinical and
clinical investigations (Chapter 3). In this section, 32 in vitro specimens were
compared to 22 in vivo specimens regarding marginal adaptation in enamel and
dentin. Clinically, replicas of baseline investigations and 6-year recalls were
compared, and in vitro we investigated replicas initially and after 2190 days of water
storage with and without thermomechanical loading for accelerated aging processes
under a SEM. Due to inferior proximal access to dentin margins, marginal adaptation
to dentin was only assessed in vitro. Here, percentages of gap-free margins dropped
from 98-100% at the beginning to 55-66% after thermomechanical loading alone and
67-75% after water storage alone and to 42-52% after both accelerated aging
mechanisms together. Enamel margins remained 100% gap-free in vitro and 86-90%
in vivo at the beginning, dropping to 85-87% after water storage and
thermomechanical loading in vitro and 74-80% in vivo. So besides some more
artifacts and overhangs due to the more challenging clinical situation, results in
marginal quality were almost identical between in vitro and in vivo specimens.
After having worked out the value of accelerated aging on resin-dentin and resin-
enamel bonding behavior, the following step was to focus on material properties of
resin composites for posterior use. Especially flexural strength and flexural fatigue
behavior have been of special interest for us due to the fact that it received increased
attention facing increasing marginal and bulk fracture rates in clinical trials dealing
with direct resin composites. A thorough evaluation of flexural fatigue characteristics
was therefore the aim of the next chapter of the present thesis (Chapter 4). Following
the same strategy as in Chapter 3, here we also simultaneously started both in vitro
and in vivo evaluations. For the in vitro part, elastic modulus, flexural strength, and
flexural fatigue limit according to the staircase method were assessed. In vivo, clinical
fracture behavior in terms of marginal breakdown and bulk fractures/chippings were
observed and correlated to the outcome detected in vitro. In vitro results showed
similar values initially, however, flexural fatigue limits were higher for Grandio
compared to Tetric Ceram. In contrast, no such differences occured in vivo up to the
108
6-year recall of the same materials having been under investigation. Only at a closer
view, facing x200 magnification of marginal breakdown sites, revealed that Tetric
Ceram showed more areas of marginal defects (7.9%) compared to Grandio (4.8%).
The ultimate instrument for definitive estimation and judgement of dental biomaterials
is still the randomized clinical long-term trial. A prospective clinical long-term trial
was carried out over a 6-year observation time, using the same restorative materials
(Solobond M/Grandio, Syntac/Tetric Ceram) previously described (Chapter 5).
Thirty patients received at least two different restorations in a random decision
according to recommendations of the CONSORT statement. Thirty-six Grandio
restorations were bonded with Solobond M, 32 Tetric Ceram restorations were bonded
with Syntac (only Class II, 52 MO/OD, 16 MOD or more surfaces). Twenty-four
cavities (35%) revealed no enamel at cervical margin, 33 cavities (49%) exhibited less
than 0.5 mm cervical enamel width. At the baseline initial recall, after 6 months, 1, 2,
4, and 6 years, all restorations were assessed according to modified United States
Public Health Service (USPHS) criteria by two independent investigators using loups
with x3.5 magnification, mirrors, probes, bitewing radiographs, impressions, and
intraoral photographs. The overall success rate was 100% after 6 years of clinical
service, while drop out of patients was 0%. Neither restorative materials nor
localization of the restorations had a significant influence on any criterion after 6
years. However, molar restorations performed worse than premolar restorations
regarding marginal integrity (4 years), restoration integrity (6, 12, 24, 48 months), and
tooth integrity (4 and 6 years). Irrespective of the resin composite used, significant
changes over time were found for all criteria applied in clinical examinations.
Marginal integrity started with a major portion of overhangs in all marginal areas
having been detected until the 1‐year recall and distinctly dropping afterwards
(overhangs at baseline 44%; 6 months: 65%; 1 year: 47%; 2 years: 6%; 4 years: 4%;
and 6 years: 3%). Beyond the 1‐year recall, more and more negative step formations
due to wear were found. Tooth integrity significantly deteriorated due to increasing
enamel cracks over time. Enamel chippings or cracks were significantly more
frequently observed in molars than in premolars. Main reasons for decreasing
“restoration integrity” were visible signs of surface roughness and distinct wear traces.
Visible wear of both materials under investigation was earlier detectable in molars
(74% bravo after 4 years) than in premolars (40% bravo after 4 years).
Summary
109
The final question remains and is addressed with the last issue of the present thesis,
i.e. what is this all about or in different words: Is clinical performance of bonded
restoratives predictable in the lab (Chapter 6)? It could be repeatedly shown that the
easiest way of predicting clinical behavior is assessment of marginal integrity. Here
the best correlation between in vitro and in vivo results can be found. The explanation
is clear: restoring real teeth with real restorations and loading them with real forces
being similar to subcritical loads in vivo finally results in realistic estimations of later
observable clinical behavior. It was clearly shown that by use of etch-and-rinse
adhesives a tight enamel seal is provided both in vitro and in vivo being well-suited to
counteract polymerization forces and to withstand occlusal stresses in the oral cavity.
However, this estimation is not correlated to the risk for secondary caries, because gap
formation not always, nor quickly results in the formation of secondary caries. Here a
complex biofilm acts on different tooth hard tissues, which is extremely hard to
simulate under in vitro conditions using an artificial mouth. So the final correlation
gap-caries is clearly not yet achieved with present investigations having been carried
out for the present thesis. Regarding fatigue behavior related to flexural strength, the
literature reveals that promising initial flexural strengths do not logically mean high
FFLs and an FFL of >30 MPa may be the critical threshold value for bulk fatigue in
order to withstand masticatory forces and clinical fatigue over its lifetime. This
furthermore supports the aspect that thorough in vitro screening of dental biomaterials
is only sufficient when long-term fatigue phenomena are considered in order to get
accelerated aging. Regarding clinical wear, few 3D laser scan studies are available in
the literature, reporting wear rates after 3 years of clinical service of ~80 µm.
Altogether, there is a certain value for accelerated in vitro testing of dental
biomaterials which is very highly esteemed because financial resources get smaller,
and ethics committees’ approval are harder to obtain.
In conclusion, the present thesis clearly shows that in vitro research will be even more
important during the next decade of research in restorative dentistry.
110
111
Samenvatting
112
Voor een veilige toepassing van tandkleurige vulmaterialen, zoals kunststof
composieten (hierna zonder meer aangeduid als composiet), is het klinisch gedrag
van groot belang. Esthetiek is in het posterieure gebied minder van belang.
Desondanks hechten onze patiënten wereldwijd veel belang aan ‘onzichtbare’
restauraties. Deze samenvatting richt zich op de relevante zaken die aan de orde
komen in de inleiding (hoofdstuk 1) van dit proefschrift om een thematische brug op
te bouwen en om een zeker kader te bieden voor toekomstige gedachtenvorming.
Composiet restauratie-materialen zijn zeer geschikt om te hechten aan de harde
tandweefsels (glazuur en dentine) wat van belang is om het tandweefsel te
ondersteunen waardoor het herstel van sterkte van het gebitselement wordt
ondersteund. Het is aangetoond dat hechting in de tandheelkunde in vele klinische
situaties veilig kan worden toegepast. Bijvoorbeeld in fissuur-afdichtingen, directe en
indirecte composietrestauraties, en in adhesief bevestigde keramische restauraties.
Hechting aan met fosforzuur geëtst glazuur is klinisch een betrouwbaar gebleken
methode. Desondanks zijn randverkleuring en rand-spleetvorming gerapporteerd als
optredende verschijnselen bij middellangetermijnonderzoek. Ook kan aan tandbeen
(dentine) worden gehecht waarbij dit levende weefsel met succes wordt afgedicht en
afgeschermd van omgevings-invloeden wat de afwezigheid van postoperatieve
overgevoeligheden verklaart. Als er geen hypergevoeligheid optreedt, wordt de
dentine afdichting als voldoende ingeschat om de vloeistofbeweging in de
dentinetubili te voorkomen. Degradatie van de hechting aan dentine met de tijd, op de
lange termijn, is een interessant fenomeen dat het onderwerp van onderzoek is van het
tweede deel van het proefschrift (Hoofdstuk 2). Het centrale uitgangspunt van dit
onderzoek was om de degradatie te versnellen in vitro door de kunststof-dentine-
verbinding aan kunstspeeksel of minerale olie (controle) bloot te stellen. Kunststof-
dentine-staafjes, aan elkaar gehecht door middel van drie verschillende ets-en-spoel
adhesiefsystemen (twee-staps systemen: Prime & Bond NT, Excite; drie-staps
systeem: All-Bond 2) werden toegepast. Na 3 jaar opslag in de beschreven media
werd het hechtvlak met transmissie elektronenmicroscopie (TEM) beoordeeld. Een
"extreme controlegroep" werd in de autoclaaf aan 121°C en 103kPa druk blootgesteld.
De TEM-beelden laten duidelijk zien dat dit extreme controle scenario niet leidt tot
het ontstaan van gedenatureerd collageen wanneer het dentine is afgedekt met een
kunststof van een dentine hechtsysteem. De hybride laag van de controlegroep die
werd blootgesteld aan minerale olie bleef vrijwel intact over de onderzoeksperiode
Samenvatting
113
van 3 jaar met een minimum aan zilverneerslag, terwijl in de testgroep blootgesteld
aan kunstmatig speeksel, uitgebreide nanolekkage werd waargenomen. Alle
ultrastructurele parameters, dat wil zeggen: de omvang van nanolekkage, interface
verkleuringen en de structuur van de collageenfibrillen in de hybride lagen en in het
onderliggende dentine waren totaal verschillend en illustreren intense
verouderingsprocessen die in dit onderzoek werden versneld met behulp van
kunstmatig speeksel.
Hechting aan dentine is verantwoordelijk voor een goede afdichting van het tandbeen
en de daaruit voortvloeiende vermindering van postoperatieve overgevoeligheden.
Daarentegen is hechting aan glazuur van belang om de restauratie houvast te geven en
voor een goede ‘onzichtbare’ overgang tussen tandweefsel en restauratie, de
randaansluiting. Daarom werd in de volgende fase van het onderzoek van dit
proefschrift de kwaliteit van de randaansluiting van een vulling met glazuur en met
dentine gelijktijdig in vitro en in vivo geëvalueerd. Dit werd gerealiseerd door het
gelijktijdig starten van beide onderzoeken om zo vergelijkbare resultaten tussen de
preklinische en klinische onderzoeken (hoofdstuk 3) te verkrijgen. In dit
deelonderzoek is de randaansluiting van composiet restauraties aan glazuur en aan
dentine met elkaar vergeleken, in vitro met 32 monsters en in vivo met 22 monsters.
Klinisch werden replica's van de baseline-resultaten met die van 6-jaar recalls
vergeleken, en in vitro werden baseline replica’s vergeleken met replica’s na 2.190
dagen blootstelling aan water met of zonder thermomechanische belasting. De
(versnelde) verouderingsprocessen werden met Scanning Electron Microscopy (SEM)
geëvalueerd. Vanwege de met direct zicht slecht toegankelijke approximale dentine-
randaansluitingen werd de randaansluiting aan dentine alleen in vitro onderzocht. In
vitro daalde het percentage van de lekvrije randaansluitingen van 98-100% bij
aanvang tot 55-66% na uitsluitend thermomechanische belasting en tot 67-75% na het
uitsluitend blootstellen aan water en tot 42-52% na blootstelling aan beide versnelde
verouderingsmechanismen. De glazuurrandaansluiting was voor de in vitro monsters
aan het begin 100% lekvrij terwijl in vitro dit variëerde van 86 - 90%. Blootstelling
aan water en thermomechanische belasting leidde tot een daling naar 85 - 87% in vitro
en naar 74 - 80% in vivo. Ondanks het feit dat de klinische situatie gepaard gaat met
wat meer artefacten en overhangende restauraties, waren de gevonden in vitro en in
vivo onderzoeksresultaten nagenoeg identiek.
114
Na meer zicht te hebben gekregen op de waarde van versnelde veroudering van de
kunststof hechting aan dentine en aan glazuur was de volgende stap in dit onderzoek
om zich te concentreren op de materiaaleigenschappen van composieten voor
toepassing in de posterieure delen van het gebit. Vooral inzicht in buigsterkte en
(buig-)vermoeiingsgedrag zijn van bijzonder belang voor het verklaren van de
randlekkage en bulkfracturen die in klinische studies met directe composieten vaak
worden gevonden. Een grondige evaluatie van de buig-vermoeidheid karakteristieken
was dan ook het doel van het volgende hoofdstuk van dit proefschrift (hoofdstuk 4).
Volgens dezelfde strategie als in hoofdstuk 3, werd hier ook tegelijkertijd
aangevangen met zowel in vitro als in vivo onderzoek. In het in vitro deel werd de
elasticiteitsmodulus, buigsterkte en buigingsvermoeiingsgrens volgens de “staircase”
methode bepaald. In vivo, werd het klinisch gedrag in termen van randbreuk,
bulkfracturen en ‘chipping’ beoordeeld en gecorreleerd met de uitkomsten van het in
vitro onderzoek. In vitro resultaten tonen bij aanvang dezelfde waarden voor de
verschillende vulmaterialen, echter de buigings/vermoeiingsgrenzen waren hoger voor
Grandio in vergelijking met Tetric Ceram. Daarentegen werden in vivo, waarbij
dezelfde materialen zijn onderzocht, geen verschillen gevonden, zelfs niet na 6 jaar.
Alleen bij een beter zicht, met x200 vergroting van de plaatsen waar randbreuk werd
gevonden, bleek dat Tetric Ceram meer randafwijkingen (7,9%) liet zien ten opzichte
van Grandio (4,8%).
Het ultieme instrument voor de definitieve bepaling van de klinische geschiktheid van
tandheelkundige biomaterialen is nog steeds gerandomiseerd klinisch onderzoek. Met
gebruikmaking van dezelfde vulmaterialen (Solobond M / Grandio, Syntac / Tetric
Ceram), eerder beschreven in de vorige hoofdstukken, werd een prospectieve
klinische langetermijnstudie uitgevoerd met een observatietijd van 6-jaar (hoofdstuk
5). Dertig patiënten ontvingen ten minste twee verschillende restauraties waarbij de
materiaalkeuze op basis van aanbevelingen van de CONSORT verklaring willekeurig
werd bepaald. Zesendertig Grandio restauraties werden met Solobond M als dentine
hechtsysteem geplaatst, 32 Tetric Ceram restauraties werden met Syntac als dentine
hechtsysteem geplaatst (alleen Klasse II, 52 MO / OD, 16 MOD of meer
oppervlakken). In vierentwintig caviteiten (35%) was geen glazuur op de cervicale
rand aanwezig, 33 caviteiten (49%) vertoonden minder dan 0,5 mm cervicale
glazuurbreedte. De restauraties werden bij aanvang, na 6 maanden, 1, 2, 4 en 6 jaar
beoordeeld, op basis van de gemodificeerde United States Public Health Service
Samenvatting
115
(USPHS) criteria door twee onafhankelijke onderzoekers met behulp van loepen met
x3.5 vergroting, spiegels, sondes, bitewing röntgenfoto's, afdrukken, en intra-orale
foto's. Het totale succespercentage van klinisch functioneren was 100% na 6 jaar, alle
patiënten zijn gedurende deze periode in onderzoeksgroep gebleven. Noch
vulmaterialen, noch lokalisatie van de restauraties hebben een significante invloed
gehad op het bepalen van de kwaliteit van functioneren na 6 jaar. Echter,
molaarrestauraties presteerden slechter dan premolaarrestauratiesmet betrekking tot de
integriteit van de randaansluiting (4 jaar), restauratie integriteit (6, 12, 24, 48
maanden), en tand integriteit (4 en 6 jaar). Ongeacht het gebruikte composiet, werden
significante veranderingen in de tijd gevonden voor alle criteria die in het klinisch
onderzoek werden geëvalueerd. De beoordeling van de randaansluiting bij aanvang
leidde tot de constatering van relatief veel overhangende randen (1 jaar) en namen
daarna af (overhang baseline 44%, 6 maanden 65%; 1 jaar: 47%; 2 jaar: 6%; 4 jaar:
4% en 6 jaar: 3%). Naast de 1-jaar recall, werden meer en meer randhoogteverschillen
als gevolg van slijtage gevonden. Tandintegriteit verslechterde als gevolg van het
toenemen van glazuurbarsten in de tijd. Glazuur-‘chipping’ of -barsten werden
significant vaker waargenomen in molaren dan in de premolaren. De belangrijkste
redenen voor het verminderen van "restauratie integriteit" waren zichtbare tekenen
van ruwheid van het oppervlak en duidelijke slijtagesporen. Voor beide materialen
was de zichtbare slijtage eerder detecteerbaar in molaren (74% bravo na 4 jaar) dan bij
premolaren (40% bravo na 4 jaar).
In hoofdstuk 6 wordt de vraag waar het in dit proefschrift om draait behandeld: zijn
klinische prestaties van adhesief geplaatste restauraties te voorspellen met
laboratoriumonderzoek? Meerdere malen is aangetoond dat de makkelijkste manier
van het voorspellen van het klinische gedrag de evaluatie van de marginale integriteit
is. Op dit gebied kan de optimale correlatie tussen in vitro en in vivo resultaten
worden gevonden. De verklaring hiervoor is duidelijk: testresultaten met natuurlijke
tanden en kiezen die zijn voorzien van echte restauraties die worden belast met de
krachten die vergelijkbaar zijn met de subkritische belastingen in vivo resulteren
uiteindelijk in een realistische inschatting van het latere klinisch waarneembare
gedrag. Het is duidelijk aangetoond dat door toepassing van ets- en spoel adhesief
systemen een stevige afdichting van het glazuur, zowel in vitro als in vivo, wordt
verkregen en dat deze hechting zeer geschikt is om de polymerisatiekrachten op te
vangen en om de functionele occlusale spanningen in de mondholte te weerstaan.
116
Echter deze schatting is niet gecorreleerd met het risico op secundaire cariës.
Randspleetvorming leidt niet altijd tot de vorming van secundaire cariës. Een
complexe biofilm ontstaat in de randspleet welke verschillend werkt op de
verschillende harde tandweefsels. De biofilm is uiterst moeilijk te simuleren onder in
vitro omstandigheden. Dus inzicht in de correlatie tussen randspleetvorming en
hetontstaan van cariës is duidelijk nog niet verkregen met de onderzoeken uit dit
proefschrift. Met betrekking tot vermoeiingskarakteristieken in relatie tot buigsterkte,
blijkt in de wetenschappelijke literatuur dat een veelbelovende buigsterkte waarde bij
aanvang niet per definitie betekent dat dit resulteert in een hoge vermoeiingslimiet
(FFL). Een FFL-waarde van > 30 MPa lijkt een kritische drempelwaarde voor
bulkvermoeidheid te zijn om de kauwkrachten langdurig te weerstaan. Dit ondersteunt
het feit dat grondige in-vitro screening van tandheelkundige biomaterialen slechts
toereikend is wanneer vermoeidheidskarakteristieken worden meegewogen. Met
betrekking tot klinische slijtage zijn er enkele studies beschikbaar in de literatuur
waarbij gebruik wordt gemaakt van 3D laser scantechnologie, waarbij de
gerapporteerde slijtage na 3 jaar klinische dienst is in de orde van grootte van ~ 80
µm. De waarde voor versnelde in-vitro testen van tandheelkundige biomaterialen is
van groot belang, de financiële middelen voor klinisch onderzoek nemen af en de
goedkeuring van ethische commissies is steeds moeilijker te verkrijgen.
Tot slot, dit proefschrift laat duidelijk zien dat het belang van in-vitro-onderzoek in de
restauratieve tandheelkunde tijdens het komende decennium zal toenemen.
117
Acknowledgements
118
To my wife Katherine Garcia-Godoy, who has been a constant beacon in my life and career. Without her this thesis would not have been possible.
To Prof. Albert Feilzer, for his constant support to this project.
To my co-promoters, Prof. Roland Frankenberger and Prof. Norbert Krämer for their vital support to this thesis. With their help this project has been possible.