Natural and mobile interactions

Long chains of HADYNAMIC RHEOLOGYFOR HYALURONIC ACID

FILLERS

Embraceperformance

WELCOME TO THE ERA OF

DYNAMIC AESTHETICS

5003

45/0

1 –

Febr

uary

201

6

RESILIENT BEAUTY

TEOSYAL®RHA 1 to 4 are medical devices class III (CE0086). Please refer to instructions of use.

4. Nusgens BV. Hyaluronic acid and extracellular matrix: a primitive molecule? Ann Dermatol Venereol 2010; 137: S3-S8.5. Stern R et al. The many ways to cleave hyaluronan. Biotech Adv 2007; 537-57.6. Stern R et al. Hyaluronan fragments: an information-rich system. European Journal of Cell Biology. 2006; 85: 699-715. 7. Cyphert JM, Trempus CS, Garantziotis S. Size matters: molecular weight specificity of hyaluronan effects in cell biology. Int J Cell Biol 2015; Article ID 563818.8. Szabo A, Szabo B, Balogh E, Zelko R, Antal I. Structural elucidation of hyaluronic acid gels after heat sterilisation. Polymer Testing 2013; 32: 1322-5.

Increasing HA stability and concentration into the dermis, and preserving its optimal length may contribute to enhance

the skin quality, its regeneration capacity and hydration to counteract ageing process4.

LMW HA

Short chains of HA

Opposite functions of the short chains of HA

With age, the quality of HA in the dermis changes : especially the HA polymers are shortened leading to a higher proportion of short chains (Low Molecular Weight (LMW) HA < 500 kDa) vs long chains4. Inadvertent degradation of the polymer during its crosslinking process may have deleterious effects and limit usefulness of the product5.

Exacerbating

inflammatory

process6

Deleterious impact on skin

health and ageing6,7

Loss of

viscoelastic

properties8

Loss of space filler and

shock absorber roles1

S H O R T C H A I N S H Y A L U R O N I C A C I D : L O N G C H A I N S V S

1. Mendoza G et al. Antioxydant profile of hyaluronan: physico-chemical features and its role in pathologies. Mini-Reviews in Medicinal Chemistry. 2009; 9: 1479-88.2. Anderegg U et al. More than just a filler – the role of hyaluronan for skin homeostasis. Experimental Dermatology. 2014; 23; 295-303. 3. Laurent TC & Fraser RE. Hyaluronan. FASEB Journal.1992; 6: 2397-404.

Thanks to these properties, hyaluronic acid maintains tissue architecture, volume and hydration1,2.

HMW HA

Structural role of the long chains of HA

In a healthy skin, native HA is made of long chains (High Molecular Weight (HMW) HA > 1 000 kDa)1. These long chains of natural HA self-organize in a 3D mobile network:

Extracellular matrix

expansion1Hygroscopy3

Viscoelasticity1,2

Tissue structure

and volume2,3Hydration2,3

Shock absorber1,2

The most commonly used rheological parameters to characterize HA gels (elastic modulus G’, viscous modulus G’’...)17-19 are usually measured under low stress and small oscillations. Such conditions do not actually reflect the mechanical stress a filler is put to by its function20.TEOXANE Laboratories decided to go beyond and developed new parameters facilitating the characterization and discrimination of various gels depending on their clinical objectives : the Strength & the Stretch.

Obtained by integrating the G’ curve, the dynamic G’ or Strength characterizes the robustness of a gel, i.e. its ability to keep its mechanical properties on a full range of stress.

The Strength is a good indicator of the structure resistance

of the gel to repeated small stress, like micromovements of the facial tissues.

T O WA R D S R E S I L I E N C E

9. Kantar Health. The European TEOSYAL®PEN trial included 30 physicians and 236 patients. 42 patients had never received manual injection with a hyaluronic acid-based filler. Report n°40HB64. 2015.10. Michaud T, et al. Facial dynamics and emotional expressions in facial aging treatments. Journal of Cosmetic Dermatology. 2014;1-13. 11. Gold MH, et al. Use of hyaluronic acid fillers for the treatment of the aging face. Clinical Interventions in Aging. 2007;2(3):369–376. 12. Breithaupt AD, et al. Next-generation dermal fillers and volumizers. Cosmet Dermatol. 2012;25:184-19. 13. Pierre S, et al. Basics of dermal filler rheology. Dermatol Surg. 2015;41(suppl 1):120-6.

Selecting a dermal filler with the right rheological properties is key to achieve the natural,

long lasting desired aesthetic result13

What do your patients need9?

Natural results and safety are among the top 3 concerns of the patients

Ideal features of a dermal filler

• Resilience properties: injectables must adapt to facial movements in a similar manner to native tissue10

• Painless11,12

• Easily injectable12

• Naturally incorporated into the patient’s dermis

• Long lasting yet reversible results12

Concerns of the patients before hyaluronic acid injection :

Trust in doctor

Natural results

Minimum side effects

Minimal pain

Financial aspect

Fear of injection

0% 20% 40% 60% 80% 100%

Extremely important

Important

Moderately important

Somewhat important

Not very important

Not at all important

14. Pomarède N et al. Hyaluronic acid injection. Ann Dermatol Venereol 2009; 136:S287-9.15. TEOXANE Patents FR2945293/WO2010131175, FR2968305/WO2012077054 and FR1260145/WO2014064633.16. TEOXANE; Data on file, measurement by an independent laboratory of the HA degree of modification by 1H NMR.

TEOXANE Laboratories innovation

‘Preserved Network’ method

Optimization of the crosslinking parameters15Temperature + Pressure + pH + Initial HA concentration & molecular weight + Mixing conditions + Duration

Maintains natural viscoelastic properties: Dynamic structure

Better preserved natural

and mobile interactions

Better preserved length

of the HA chains

Less modified HA : lower

BDDE rate (1.9 - 4.0%)16

Long chains > short chains

Natural and mobileinteractions BDDE

From native HA to dermal filler

Classical crosslinking methodClassical crosslinking methods require harsh conditions, resulting in a higher rate of short chains and thus a higher BDDE rate (5.0 - 10.0%) to obtain a monophasic cohe-sive gel14:

Damages natural viscoelastic properties: Rigid structure

Short chains > long chains

BDDE

17. Falcone SJ, Berg RA. Temporary Polysaccharide Dermal Fillers: A Model for Persistence Based on Physical Properties. Dermatol Surg 2009; 35: 1238-43.18. Sundaram H, Cassuto D. Biophysical Characteristics of Hyaluronic Acid Soft-Tissue Fillers and Their Relevance to Aesthetic Applications. Plast Reconstr Surg 2013 Oct; 132(4 Suppl 2): 5S-21S.19. Kablik J, Monhett GD, Yu LP, Chang G, Gershkovich J. Comparative Physical Properties of Hyaluronic Acid Dermal Fillers. Dermatol Surg 2009; 35: 302–312.20. Kausch HH. Matériaux Polymères: Propriétés Mécaniques et Physiques. PPUR presses polytechniques 2001: 262.

By associating the Strength and Stretch concepts,

dynamic rheology brings a holistic and comprehensive

response to the gel behaviour

To complete this dynamic approach and considering that the real deformations a filler is submitted to are actually beyond the linear viscoelastic region, the next step was to assess the gel behavior in the non-linear viscoelastic region20.

TCH

Under normal conditions of use in aesthetic medicine an HA gel undergoes:

The conventional rheology measures do not provide information about the gel behavior under such large deformations.

Obtained by a new testing approach, deformation by creep, the Stretch

indicates the malleability and adaptability of the gel to a determined stress

in the non-linear viscoelastic region.

T H E DY N A M I C R H E O L O G Y C O N C E P T

Strength: resistance to compression

Stretch

➜➜ ➜

50

150

200

Linear viscoelastic region

«G' dynamique» = Strength

Non-linearviscoelastic region

Stress τ (Pa)

Robustness of the HA network structure depending on the stress intensity

Facial dynamismUltra thin needleStress applied by the injector