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Statement of research interests

Introduction

Research in Biomaterials is undergoing a paradigm shift. Biomaterial can be defined as any

material used to make devices to replace a part or a function of the body in a safe, reliable,

economic, and physiologically acceptable manner. A biomaterial is a synthetic or natural

material used to replace part of a living system or to function in intimate contact with living

tissue.

First name: Esmaeil

Surname: Biazar

Nationality: Iranian

Place of Birth: Ramsar City, Mazandaran , Iran

Status: Single

Birthdate: 1977

Languages: Persian, English

Address: Department of Biomedical Engineering, IAU-Branch of Tonekabon , Tonekabon, Iran,

P.O.Box:4691814754

Tel.: +98-11-5525-5718 , 09118931556

Fax: +98-11-5427-4409

e.biazar@toniau.ac.ir ,kia_esm@yahoo.com ,www.toniau.ac.ir

Site address:

www.Biomaterialsengineering.com

Esmaeil Biazar

Assistant professor

Ph.D. Biomedical Engineering (Biomaterials)

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In this context, my principle research interests are synthesis and designs of biomaterials for

biomedical and tissue engineering. I use direct experimental investigation for interpretation of

results. Hereinafter, I will mention some of my works in this field.

• Ph.D: Biomedical Engineering (Biomaterials) from Science and Research University

(Tehran, Iran; 2006-2011).

Thesis title: Design of intelligent surfaces by graft co-polymerization of NIPAAm on PS surface

under UV radiation and its cellular investigation.

• M.Sc: Biomedical Engineering (Biomaterials) from Iran University of Science and

Technology (Tehran, Iran; 2003-2005).

Thesis title: The Effect of mechanical activation on size reduction of crystalline acetaminophen

drug particles.

• B.Sc: Applied Chemistry from Mazandaran University (Babolsar , Iran; 1998-2002).

MSc work

When I was a Master student in Iran University of Science and Technology (Tehran, Iran) I

worked on nano drugs and effect of mechanical activation on size reduction of crystalline

acetaminophen drug particles and its toxicological investigations [1,2].

PhD works

When I was a PhD student at Science and Research University (Tehran, Iran), my first work was

design of intelligent surfaces by graft co-polymerization of NIPAAm on polystyrene surface

under UV, Gamma radiations and its cellular investigations. Characterization has been done by

means of scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR

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and AFTIR), transmission-electron microscope (TEM) and differential scanning calorimetric

analysis (DSC) , thermo gravimetric analysis (TGA) and Contact angles[3,4]. I was evaluated

relation between surface roughness and cell adhesion by gravimetric, SEM, AFM, contact angle

measurement and cellular analyses. The gravimetric analysis clearly indicated an increase in the

grafting by adding 10% methanol to water. The study of surface topography by atomic force

microscopic (AFM) images showed an increase in the surface roughness and as a result of which,

a decrease in wettablity was observed. At 37 °C, epithelial cells were well attached and

proliferated on the grafted surfaces, while these cells were spontaneously detached below 32 °C

in the absence of any enzymes. Moreover, MTT assay and SEM images indicated good cell

viability and an increase in cell adhesion caused by the roughness increase. The results of this

study revealed the great potential of PNIPAM-grafted polystyrene for being used in the

biomedical fields such as cell sheet engineering and cell separation [5].

After PhD

In one team work, we have synthesized magnetic chitosan nanocomposite particles. In this study,

chitosan was chemically-bonded on the surface of magnetite nanoparticles, where 3-

aminopropyltriethoxysilane (APTES) was employed in advance to modify the magnetite

nanoparticles’ surface. Modified and unmodified magnetic nanoparticles were characterized by

FT-IR, TGA, TEM, VSM, DLS and MTT analyses. FT-IR, TGA and DLS results definitely

showed surface modification of magnetic nanoparticles with APTES and chitosan. TEM images

revealed the morphology of the obtained nanocomposite particles and their magnetic properties

were studied by evaluation of corresponding hysteresis loops via VSM analysis. MTT assay and

cellular results depicted high viability of coated magnetic nanoparticles with chitosan and their

usefulness in biomedical field, especially in cell separation applications [6].

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In another team work, we have fabricated the different intelligent films and surfaces by chemical

and physical grafting and investigated their cellular properties for cell sheet engineering [7,8].

Current researches

In my current researches, I have increased the scope of work as follows:

Bone regeneration

1. Design of fluorapatite–hydroxyapatite nanoparticles synthesis to obtain more control on shape

and morphology using the sol-gel method. Powders obtained from the sol-gel process were

studied after they were dried at 80°C and heat treated at 550°C. The degree of crystallinity,

particle and crystallite size, powder morphology, chemical structure, and phase analysis were

investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier

transform infrared spectroscopy (FTIR), and zeta sizer experiments. The results of XRD analysis

and FTIR showed the presence of hydroxyapatite and fluorapatite phases. The in vitro behavior

of powder was investigated with mouse fibroblast cells. The results of these experiments

indicated that the powders were biocompatibile and would not cause toxic reactions. These

compounds could be applied for hard-tissue engineering [9,10].

Electron microscopic images of fluorapatite–hydroxyapatite nanoparticles [9].

2. In other studies, calcium phosphate nanoparticles such as hydroxyapatite (HA)/fluorapatite

(FA), with chitosan gel filled with unrestricted somatic stem cells (USSCs) were used for healing

calvarial bone in rat model. The healing effects of these injectable scaffolds, with and without

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stem cells, in bone regeneration were investigated by computed tomography (CT) analysis and

pathology assays after 28 days of grafting. The results of CT analysis showed that bone

regeneration on the scaffolds, and the amounts of regenerated new bone for USSC scaffold was

significantly greater than the scaffold without cell and untreated controls. Therefore, the

combination of injectable scaffolds especially with USSC could be considered as a useful

method for bone regeneration [11-13].

Implantation of scaffold in defected bone (In-vivo) [11].

Nerve regeneration

3. Cellular orientation control is important for neural tissue regeneration. Design of oriented

structures for cells with suitable features can be used in tissue engineering. One of the methods

of cellular orientation with the aim of regenerating which damaged tissues is utilizing oriented

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biocompatible substrates. This paper reports a one-step method with different solvents to

fabricate porous micro-patterned 2-D Polyhydroxybutyrate (PHB) scaffold sheets. The results

indicated that the porosity and pore morphology of the scaffolds are viable with respect to

proliferation rate, and a micro-pattern for cell alignment. The cells were successfully oriented on

micro grooved polymeric substrate which can be used for axon guidance and nerve regeneration.

Preliminary experiments indicate that the 2-D scaffold sheets are very promising as basis for

building 3-D scaffolds [14,15].

SEM images of oriented scaffolds.

4. An oriented poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit has been used to

evaluate its efficiency based on the promotion of peripheral nerve regeneration in rats. The

oriented porous micro-patterned artificial nerve conduit was designed onto the micro-patterned

silicon wafers, and then their surfaces were modified with oxygen plasma to increase cell

adhesion. The designed conduits were investigated by cell culture analyses with Schwann cells

(SCs). The conduits were implanted into a 30 mm gap in sciatic nerves of rats. Four months after

surgery, the regenerated nerves were monitored and evaluated by macroscopic assessments and

histology and behavioral analyses. This study proves the feasibility of the artificial nerve graft

filled with SCs for peripheral nerve regeneration by bridging a longer defect in an animal model

[16].

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SEM images of oriented guides and Schwann cells cultivated on it [16].

5. It has been confirmed that nanofibrous nerve conduit can promote peripheral nerve

regeneration in rats. In our studies, we used different nanofibrous nerve conduit such as PHBV,

modified PHBV with collagen, chitosan or gelatin, Silk (random and aligned nanofibers),

laminin to bridge a long gap in the peripheral nerve. These nanofibers assessed by cultivation of

Schwann cells[17-20].

SEM images of nanofibrous guides and Schwann cells cultivated on it[17-20].

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6. In other studies, we used nanofibrous nerve conduits to bridge a 30-mm-long gap in the rat

sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were observed

and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been

reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There

were Schwann cells and glial cells in the regenerated nerves. Masson’s trichrome staining

showed that there were no pathological changes in the size and structure of gastrocnemius

muscle cells on the operated side of rats. Within 4 months after surgery, rat sciatic nerve

functional recovery was evaluated per month by behavioral analyses, including toe out angle, toe

spread analysis, walking track analysis, extensor postural thrust, swimming test, open-field

analysis and nociceptive function. Results showed that rat sciatic nerve functional recovery was

similar after fibrous conduit and autologous nerve grafting. These findings suggest that

nanofibrous nerve conduits are suitable for repair of long-segment sciatic nerve defects[21-24].

Implantation of neural guides in defected sciatic nerve (Rat model) and their histological & behavioral

investigations (In-vivo)[21-24].

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Skin regeneration

7. In defects of partial-thickness injury, regeneration occurs simply under the conservative

treatments. However, for full-thickness skin defects, complexity processes are required. Stem

cell therapy and tissue engineering have emerged as a promising new approach in almost every

medicine specialty. In previous studies, we designed bio-polymeric scaffolds (synthetic or

natural polymers or their blend) with different structures and morphologies (nanofibers and

sponges) or modified the biopolymers by physical (Plasma treatment) or chemical processes for

skin regeneration[25-31].

SEM images of the scaffolds (porous (sponge) and nanofiber)[25-27].

8. In other studies, we evaluated the wound-healing effects of unrestricted somatic stem cells

loaded in nanofibrous or sponge PHBV scaffolds (cross linked with chitosan or gelatin),

implanted into the full thickness skin defects of rats. Afterwards, the scaffolds were evaluated by

structural, microscopic, physical and mechanical assays and cell culture analyses. Defects were

treated with the scaffolds without and with USSCs. MTT assay, immunostaining, and wound

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pathology were performed for groups twenty one days after implantation. Cellular experiments

showed a better cell adhesion, growth and proliferation inside the cross-linked scaffolds

compared to un-cross linked ones. In animal models, all groups, excluding the control group,

exhibited the most pronounced effect on wound closure, with the statistically significant

improvement in wound healing being seen at post-operative day 21. Histological and

immunostaining examinations of healed wounds from all groups, especially the groups treated

with stem cells. Thus, the grafting of chitosan-cross-linked nanofibrous scaffold loaded with

USSC showed better results during the healing process of skin defects in rat models[26-31].

Histology of wounds by H&E staining in the different scaffolds without and with stem cells on post-operative

day 21[27].

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Cornea regeneration

9. The aim of these studies was to develop a suitable scaffold for limbal stem cell (LSC)

expansion that can serve as a potential alternative substrate to replace human amniotic

membrane. We developed many scaffolds with different morphologies (sponge, nanofiber

(aligned or random), and hydrogels) from different synthetic and natural biopolymers (gelatin,

silk, polyhydroxyalkanoates ,..)[32-36].

Intelligent hydrogel (Chitosan /Gelatin)[36].

SEM images of nanofibrous scaffold and limbal stem cell cultured on it [34].

Carbon nanotubes for drug delivery

10. In another team work, we have functionalized of carbon nanotubes with different derivatives

and investigated their toxicity [37-41].

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SEM images of modified SWNTs [41].

11. In other study, carbon nanotubes (SWCNTs,MWCNT) pre-functionalized covalently with a

paclitaxel (PTX) anticancer drug and folic acid (FA) as a targeting agent for many tumors. The

samples investigated and evaluated by different analyses such fourier transform infrared (FTIR),

scanning electron microscope (SEM), thermal gravimetric analysis (TGA), absorption

spectroscopic measurements (UV-visible) and elemental analysis. Results showed well

conjugation of targeting molecule and anticancer drug on carbon nanotube surfaces. This work

demonstrated that the CNT-PTX-FA system was a potentially useful system for the targeted

delivery of anticancer drug [41].

Conjugation process of PTX and FA onto amide functionalized SWNT [41].

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Future plans

1) Designing the intelligent films using PNIPAm and natural biopolymers for increasing

the cell viability, adhesion and detachment (Cell sheet engineering).

2) Modification of intelligent chitosan hydrogels as an injectable design loading cells and

growth factor to obtain better cellular viability, adhesion and growth promotion for tissue

engineering especially cartilage and bone regeneration (Intelligent hydrogel).

3) Modification of nanofibrous scaffolds coated by silk and collagen biopolymers as a

neural guide (Neural engineering)..

4) Designing the oriented & cross-linked porous tubes from silk and collagen

biopolymers as a neural guide (Neural engineering)..

5) Designing of nanofibrous scaffolds from cross-linked collagen, elastin and silk with

synthetic biopolymers as a scaffold for loading cells and growth factor for skin

regeneration (Skin regeneration).

6) Designing the oriented cross-linked lamellas from collagen using magnetic

nanoparticles for cornea stromal regeneration (Cornea regeneration).

7) Designing the cross-linked scaffolds (oriented, random and others structures) from

synthetic and natural biopolymers for cornea epithelial and endothelial regeneration

(Cornea regeneration).

8) Designing the keratoprostheses using novel technologies (electro-spinning and 3D

printing) (Artificial Cornea).

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References

1. Esmaeil Biazar and et al. The Effect of acetaminophen nanoparticles of liver toxicity in a rat model.

Int.J.Nanomed. 2010:5:197-2011(ISI / Impact factor: 4.383).

2. Esmaeil Biazar and et al. The Effect of the mechanical activation on size reduction of crystalline

acetaminophen drug particles. Int.J.Nanomed.2009:4:283-287(ISI / Impact factor: 4.383).

3. Esmaeil Biazar and et al. The Effect of Gamma Radiation Dose on the Surface Modification of

Polystyrene Film by Nanometric Grafting Poly(N-isopropylacrylamide) for Cell Engineering

Applications. Int.J.Nanomed. 2010:5:1-9 (ISI / Impact factor: 4.383).

4. Esmaeil Biazar and et al. Cell sheet engineering: solvent effect on nanometric grafting of poly-n-

isopropylacrylamide onto polystyrene substrate under ultraviolet radiation. Int.J.Nanomed. 2011:6 295–

302(ISI / Impact factor: 4.383).

5. Esmaeil Biazar and et al. Cell adhesion and surface properties of poly styrene surfaces grafed with

Poly(N-Isopropylacrylamide. Chinese j polym sci. 2013;31(11):1509-1518 (ISI/Impact factor: 1.835).

6. Esmaeil Biazar and et al. Preparation of Magnetic Chitosan Nanocomposite Particles and Their

Susceptibility for Cellular Separation Applications. Journal of Colloid Science and Biotechnology.

2012;1:1–7 (American scientists society, PUBMED).

7. Esmaeil Biazar and et al. Harvesting epithelial cell sheet based on thermo- sensitive hydrogel.

Journal of Paramedical Sciences (JPS). 2010;1(3):27-33(ISC,PUBMED).

8. Esmaeil Biazar and et al. Synthesis and properties of thermo- sensitive hydrogels based on

PVA/Chitosan/PNIPAAm. Oriental journal of chemistry. 2011; 27(4):1443-1449 (ISI).

9. Esmaeil Biazar and et al. Synthesis of fuorapatite–hydroxyapatite nanoparticles and its toxicity

investigations. Int.J.Nanomed. 2011:6 197–201(ISI / Impact factor: 4.383).

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10. Esmaeil Biazar and et al. Mechanical properties of chitosan-starch composite filled hydroxyapatite

micro and nano powders. J Nanomater. 2011; doi:10.1155/2011/391596 (ISI / Impact factor: 1.644).

11. Esmaeil Biazar and et al. Bone formation in calvarial defects by injectable nanoparticular scaffold

loaded with Stem Cells. Expert Opin. Biol. Th. (2013) 13(12):1653-1662 (ISI / Impact factor: 3.743).

12. Esmaeil Biazar and et al. Bone reconstruction in rat calvarial defects by chitosan/hydroxyapatite

nanoparticles scaffold loaded with unrestricted somatic stem cells. Artif Cell Nanomed B. 2015; 43:

112–116 (ISI / Impact factor: 1.015).

13. Esmaeil Biazar, Saeed Heidari Keshel. Electrospun Poly hydroxybutyrate-co-hydroxyvalerate

(PHBV)/ Hydroxyapatite Scaffold with Unrestricted Somatic Stem Cells (USSCs) for Bone

Regeneration. ASAIO J. 2015;61(3):357-365(ISI / Impact factor: 1.516).

14. Esmaeil Biazar and et al. Design of an oriented porous polymeric guide for neural regeneration.

Int. J. Polym Mater Po. 2014, 63: 753–757 (ISI/Impact factor: 3.568).

15. Esmaeil Biazar and et al. Solvent effect in phase separation for fabrication of micro-patterned

porous scaffold sheets. Int. J. Polym Mater Po. 2016, In press (ISI/Impact factor: 3.568).

16. Esmaeil Biazar and et al. Rat Sciatic Nerve Reconstruction Across a 30 mm Defect Bridged by an

Oriented Porous PHBV Tube With Schwann Cell as Artificial Nerve Graft. ASAIO J . 2014; 60:224–233

(ISI / Impact factor: 1.516).

17. Esmaeil Biazar and et al. Review: Types of neural guides and using nanotechnology for peripheral

nerve reconstruction. Int.J.Nanomed. 2010:5 839–852 (ISI / Impact factor: 4.383).

18. Esmaeil Biazar and et al. Gelatin-Modified Nanofibrous PHBV Tube as Artificial Nerve Graft for

Rat Sciatic Nerve Regeneration. Int. J. Polym Mater Po. 63: 330–336 (ISI/Impact factor: 3.568).

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19. Esmaeil Biazar and et al. Chitosan-cross linked nanofibrous PHBV nerve guide for rat sciatic nerve

regeneration across a defect bridge. ASAIO J. 2013; 59:651–659 (ISI / Impact factor: 1.516).

20. Esmaeil Biazar et al. Development of oriented nanofibrous silk guide for repair of nerve defects.

Int. J. Polym Mater Po..2015; In press (ISI/Impact factor: 3.568).

21. Esmaeil Biazar and et al. Rat sciatic nerve regeneration across a 30-mm defect bridged by a

nanofibrous PHBV and Schwann cell as artificial nerve graft. Cell Commun Adhes. 2013: 20(1-2):41-49

(ISI / Impact factor: 2.414).

22. Esmaeil Biazar and et al. Behavioral evaluation of regenerated rat sciatic nerve by a nanofibrous

PHBV conduit filled with Schwann cell as artificial nerve graft. Cell Commun Adhes. 2013;20(5):93-

103 (ISI / Impact factor:2.414).

23. Esmaeil Biazar and et al. Nanofibrous nerve conduits for repair of 30-mm-long sciatic nerve

defects. Neural Regen Res. 2013;8(24):2266-2274 (ISI / Impact factor:0.22).

24. Esmaeil Biazar and et al. Efficacy of nanofibrous conduits in repair of long segment sciatic nerve

defects. Neural Regen Res. 2013;8(27):2501-2509 (ISI / Impact factor: 0.22).

25. Esmaeil Biazar and et al. Fabrication of Collagen-Coated Poly (beta-hydroxy butyrate-co-beta-

hydroxyvalerate) Nanofiber by Chemical and Physical Methods. Oriental journal of chemistry. 2011;

27(2): 385-395 (ISI).

26. Esmaeil Biazar and et al. Regeneration of Full-Thickness Skin Defects Using Umbilical Cord

Blood Stem Cells Loaded into Modified Porous Scaffolds. ASAIO J .2014; 60:106–114. (ISI / Impact

factor: 1.516).

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27. Esmaeil Biazar and et al. Effects of chitosan cross linked nanofibrous PHBV scaffold combined

with mesenchymal stem cells on healing of full-thickness skin defects. J. Biomed Nanotechnol.

2013;9(9):1471-1482( ISI / Impact factor:5.338).

28. Esmaeil Biazar and et al. Unrestricted Somatic Stem Cells Loaded in Nanofibrous Scaffolds as

Potential candidate for Skin Regeneration. Int. J. Polym Mater Po. 2014,63: 741–752 (ISI/Impact factor:

3.568).

29. Esmaeil Biazar and et al. The healing effect of unrestricted somatic stem cells loaded in

nanofibrous Polyhydroxybutyrate-co-hydroxyvalerate scaffold on full-thickness skin defects. J Biomater

Tiss Eng. 2014; 4:20-27(ISI / Impact factor: 2.066).

30. Esmaeil Biazar and et al. The healing effect of unrestricted somatic stem cells loaded in collagen-

modified nanofibrous PHBV scaffold on full-thickness skin defects. Artif. Cell. Nanomed B . 2014;

42:210-216 (ISI / Impact factor: 1.015).

31. Hoda bahrami , Esmaeil Biazar and et al. Human unrestricted somatic stem cells loaded in

nanofibrous PCL scaff old and their healing effect on skin defects. Artif Cell Nanomed B. 2015; In press

(ISI / Impact factor: 1.015).

32. Alireza Baradaran-Rafii, Esmaeil Biazar and Saeed Heidari-keshel. Cellular Response of Limbal

Stem Cells on Polycaprolactone Nanofibrous Scaffolds for Ocular Epithelial Regeneration. Curr Eye

Res. In press. 2015(ISI / Impact factor: 1.639).

33. Alireza Baradaran-Rafii, Esmaeil Biazar and Saeed Heidari-keshel. Cellular Response of Limbal

Stem Cells on Poly (Hydroxybuthyrate-co-Hydroxyvalerate) Porous Scaffolds for Ocular Surface

Bioengineering. Int. J. Polym Mater and Polym Biomater.2015; 64: 815–821 (ISI/Impact factor: 3.568).

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34. Alireza Baradaran-Rafii, Esmaeil Biazar and Saeed Heidari-keshel. Cellular Response of Limbal

Stem Cells on PHBV/Gelatin Nanofibrous Scaffold for Ocular Epithelial Regeneration. Int. J. Polym

Mater and Polym Biomater.2015; 64: 879–887(ISI/Impact factor: 3.568).

35. Alireza Baradaran-Rafii, Esmaeil Biazar and Saeed Heidari-keshel. Oriented Nanofibrous Silk as a

Natural Scaffold for Ocular Epithelial Regeneration. J Biomater Sci Polym Ed. 2015;26:1139-1151. (ISI

/ Impact factor: 1.648).

36. Esmaeil Biazar. Saeed Heidari Keshel, Maryam Rostampour, Golbahar Khosropour, Atefesadat

Bandbon B, Alireza Baradaran-Rafii. Derivation of Epithelial-like Cells from Eyelid Fat Derived Stem

Cells in Thermosensitive Hydrogel. Journal of Biomaterials Science Polymer Edition. 2015. DOI:

10.1080/09205063.2015.1130406 (ISI/Impact factor: 1.65).

37. Javad Azizian, Hasan Tahermansouri ,Esmaeil Biazar , Saeed heidari , Davood chobfrosh Khoei

.Functionalization of carboxylated multiwall nanotubes with imidazole derivatives and their toxicity

investigations. Int.J.Nanomed. 2010:5 907–914(ISI / Impact factor: 4.383).

38. Hasan Tahermansouri and Esmaeil Biazar. Functionalization of carboxylated multi-wall carbon

nanotubes with 3,5-diphenyl pyrazole and an investigation of their toxicity. Carbon. 2013; 63:594 (ISI /

Impact factor: 6.196).

39. Hasan Tahermansouri and Esmaeil Biazar . Functionalization of carboxylated multi-wall carbon

nanotubes with 3,5-diphenyl pyrazole and an investigation of their toxicity. New Carbon Mater. 2013;

28(3):199–207(ISI / Impact factor: 0.979).

40. Hasan Tahermansouri, Yaser Aryanfar, and Esmaeil Biazar. Synthesis, Characterization, and the

Influence of Functionalized Multi-Walled Carbon Nanotubes with Creatinine and 2-

Aminobenzophenone on the Gastric Cancer Cells. B Korean Chem. Soc. 2013; 34(1):149 (ISI / Impact

factor: 0.797).

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41. Sara Tavakolifard , Esmaeil Biazar , Khalil Pourshamsian & Mohammad H. Moslemin. Synthesis

and evaluation of single-wall carbon nanotube-paclitaxel-folic acid conjugate as an anti-cancer targeting

agent. Artif Cell Nanomed B. 2015; In press (ISI / Impact factor: 1.015).