Biomimetic Scaffolds for Ligament Tissue Engineering
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The primary objective of my thesis was to investigate the effect of crimp-like fibrous scaffolds on bovine fibroblasts and to develop a scaffold for anterior cruciate ligament (ACL) tissue engineering. To achieve this objective, fibrous biodegradable polymeric scaffolds were fabricated, which upon relaxation developed a crimp-like structure, which resembled the crimp seen in native collagen. The understanding of the crimp mechanism allowed for controlling crimp-like patterns in various polymer fibre systems, and was determined to be due to residual stress coupled with an operating temperature (Top) above the glass transition temperature of the polymer (Tg). The benefit of crimp was evaluated by seeding fibroblasts on crimp-like fibres that were subjected to dynamic mechanical loading. The results showed a significant increase in extracellular matrix (ECM) accumulation by fibroblasts that experienced crimp unfolding. In addition, fibroblasts seeded on mechanically stimulated crimp-like fibrous scaffolds formed ECM bundles that resembled collagen fibre fascicles. Two separate studies were conducted to fabricate fibrous scaffolds with high modulus: one on thermoplastic polyesters and the other on a photocrosslinkable polyester. Of the thermoplastic polyesters investigated, poly(L-lactide-co-D,L-lactide) P(LLA-DLLA) exhibited the highest modulus, and was the most resistant to hydrolytic degradation. These fibres were placed in a heated aqueous environment to exhibit a crimp-like pattern similar to that of native collagen. Bovine fibroblasts were shown to attach, proliferate and deposit ECM on the surface of the P(LLA-DLLA) fibrous scaffolds. In addition, the deposited ECM appeared to be organized in distinctive bundles that resembled fascicles found in native ACL. However, upon crimp unfolding the crimp was not completely recovered. Photocrosslinkable poly(L-lactide-co-trimethylene carbonate cinnamate) P(LLA-TMC cinnamate) fibres in addition to supporting cell proliferation and ECM accumulation, completely recovered their crimp-like pattern, via [2 + 2] cycloaddition of the cinnamate groups. The recovery of crimp upon unfolding is a novel design feature incorporated into electrospun fibres as it innately mimics the function of collagen fibres found in the ACL. From the results obtained it is evident that crimp and its unfolding are key design features/conditioning techniques that need to be incorporated into fibrous scaffolds that possess high modulus, intended for ligament tissue engineering.