Bio-Medical Sciences and Engineering PhD Thesis Defense by Muhammad Anwaar Nazeer

KOÇ UNIVERSITY

GRADUATE SCHOOL OF SCIENCES & ENGINEERING

BIO-MEDICAL SCIENCES AND ENGINEERING

PhD THESIS DEFENSE BY MUHAMMAD ANWAAR NAZEER

Title: Design, Fabrication and Characterization of Biodegradable Scaffolds for Tissue Engineering and Regenerative Medicine Applications

Speaker: Muhammad Anwaar Nazeer

Time: August 29, 2018, 11:00 AM

Place: Polymer Lab (SCI-246)

Koç University

Rumeli Feneri Yolu

Sariyer, Istanbul

Thesis Committee Members:

Prof. Dr. İskender Yılgör (Advisor, Koç University)

Prof. Dr. Halil Kavaklı (Koç University)

Assoc. Prof. Dr. Funda Yağcı Acar (Koç University)

Assoc. Prof. Dr. Pınar Yılgör Huri (Ankara University)

Assoc. Prof. Dr. Kadriye Tuzlakoğlu (Yalova University)

Abstract:

Biocompatible and biodegradable scaffolds for tissue engineering and regenerative medicine applications were developed. Bone and skin tissue engineering applications were focused throughout the study. Biomaterials such as hydroxyapatite (HA), chitosan (CS) and poly(lactic acid) (PLA) were used to fabricate scaffolds for potential bone regeneration applications. HA was synthesized through different production routes via sol-gel process. The process was critically analyzed and evaluated for synthesis of pure HA. Nano-composite scaffolds of CS/HA were fabricated through simple solvent casting method. Selection of proper solvent media (formic acid, a green solvent) produced stable and well defined dispersion of HA that resulted in intercalated structural composites. Furthermore, 3D PLA scaffolds were developed through fused deposition modeling and CS/HA were incorporated in these scaffolds. Formic acid enabled embedding of CS/HA through chemical etching of PLA surfaces. These scaffolds were analyzed in-vitro by seeding U2-OS human osteosarcoma cells. Scaffolds modified with CS/HA showed higher cell proliferation as compared to unmodified ones. The scaffolds developed in this study show great potential for use as substrates for bone tissue engineering applications.

For skin tissue engineering applications, polycaprolactone (PCL) and the blend of a polyurethane (PU) prepared through stoichiometric reaction of PCL (Mn=2000 g/mol) and 1,6-hexamethylene diisocyanate (HDI) and silk fibroin (SF) were used. PCL was synthesized through ring opening polymerization of Ɛ-caprolactone in the presence of T-9 catalyst and 1,2-bis(3-aminopropoxy)ethane as initiator. SF was obtained by degumming of silk cocoons through a novel process developed in this study and subsequent dissolution. Nano-fibrous scaffolds of PCL and PU with and without different amounts of SF were prepared through a “green” electrospinning process in formic acid, which is a low toxicity Q3C class 3 solvent, rather than commonly used class 2 solvents such as tetrahydrofuran (THF) and dimethylformamide (DMF). Successful addition of SF and its effect on these scaffolds was analyzed through various characterization techniques. In-vitro analysis was done by seeding Human BJ and NIH/3T3-Mouse embryo fibroblast cells on PCL, PCL/SF and PU, PU/SF scaffolds respectively. ATP and MTT cytotoxicity analyses revealed significant enhanced proliferation of fibroblast cells as compared to pristine PCL and PU scaffolds. We believe these novel composite scaffolds with good mechanical properties and bioactivity can be used for skin tissue engineering applications.