Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemical and Biochemical Engineering

Supervisor

Drs. Kibret Mequanint

2nd Supervisor

Amin S. Rizkalla

Joint Supervisor

Abstract

Treatments of bone injuries and defects have been largely centered on replacing the lost bone with tissues of allogeneic or xenogeneic sources as well as synthetic bone substitutes, which in all lead to limited degree of structural and functional recovery. As a result, tissue engineering has emerged as a viable technology to regenerate the structures and therefore recover the functions of bone tissue rather than replacement alone. Hence, the current strategies of bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix (ECM) as templates onto which cells attach, multiply, migrate and function.

In this thesis work, a new class of biodegradable and bioactive organic-inorganic hybrid biomaterials were synthesized via a sol-gel process. Poly (e-caprolactone) (PCL) and tertiary bioactive glass (BG) were used as the polymer and inorganic phases, respectively. The polymer chains were successfully introduced into the inorganic sol while the networks were formed. The PCL/BG hybrid biomaterials exhibited an amorphous structure with spatially distributed calcium atom. Hydrogen bonding was formed to link organic and inorganic phases at molecular scale via the carbonyl group of the PCL and the silanol hydroxyl group of the silica network. The presence of surface silanol groups (Si-OH) as well as the homogenously incorporated Ca2+ and PO4-3 ions contributed to modulate the rate and total amount of bone-like HA deposition on the PCL/BG hybrid surfaces. The compressive modulus and strength of the PCL/BG hybrids increased with the decrease in PCL content. The highest values were achieved at the lowest PCL content (10 wt. %) and were around, 90 MPa and 1.4 GPa, respectively. The cell viability study revealed that the PCL/BG hybrid biomaterials (100 – 500 µg/ml) have no toxicity due to the hybridization process. The ability to tailor the bioactivity and mechanical properties of these novel PCL/BG hybrid materials could be used as screening tool to fabricate multifunctional PCL/BG hybrid biomaterials for specific biomedical applications.

The addition of PCL provided the way to control the rheological properties of the sol by reducing the rate of gelation, which in turn facilitated the successful fabrication of 3D PCL/BG hybrid scaffolds by electrospinning process. The 3D PCL/BG fibrous scaffolds exhibited high porosity, greatly improved wettability, significantly enhanced mechanical properties, and in vitro bone-like apatite formation ability. These scaffolds demonstrated excellent biocompatibility, with an evidence of supporting cell attachment and proliferation. Furthermore, early and enhanced expressions of collagen type I (Col I), alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OCN) compared with PCL scaffolds demonstrated the potential of PCL/BG hybrid scaffolds for promoting bone regeneration. The work described herein provides strong evidence that O/I hybrid scaffolds have a potential in bone regeneration, and paves a way for future studies.