Design of Biomimetically Inspired Hydroxyapatite-gelatin Based Composite for Bone Scaffold Application

摘要

Bone tissue engineering (BTE) requires a sturdy biomimetic scaffold for restoration of large bone defects. This dissertation describes the progress made in improving our previously developed Gemosil composite consisting of Hydroxyapatite-Gelatin (HAp-Gel) with silane cross-linker as a potential scaffold. Our initial goal was to further improve the mechanical strength of the composite. We first successfully doubled the mechanical strength of the composite through adding selected co-solvent during the sol-gel process. We further experimentally confirmed that the improvement of the mechanical strength is due to the improved morphology of both the silane network and the Gemosil composite. Unfortunately, the scaffold fabricated from this composite (even with the newly optimized processing condition) underwent rapid degradation in water, and rapidly lost its mechanical strength.;To mitigate this degradation issue, we attempted to incorporate a cross-linkable polymer into the Gemosil composite, aiming to further increase mechanical strength of the Gemosil composite with an additional polymeric network (i.e., reinforcing network). Specifically, we synthesized a new biocompatible and biodegradable copolymer, poly(L-lactide-co-propargyl carbonate) with pendent catechol functional groups. These catechol functional groups served as "liaison" molecules to help to improve the interfacial adhesion between the polymer network and the various components of the Gemosil. We demonstrated that through incorporating this copolymer together with mussel-inspired dopamine into Gemosil system, the compressive strength of the scaffold could be improved by 20% under aqueous condition.;Finally, despite the impressive adhesive and coating property of dopamine/polydopamine demonstrated by us and others, polydopamine (PDA) has its own limitations. For instance, PDA's black color is not favored for clinical applications and its polymerization mechanism is still elusive. We synthesized a series of dopamine analogues with different alkyl chain lengths between the catechol and the amine. We found all of these new dopamine analogues were able to polymerize. Through studying the adhesive and coating ability of these new dopamine analogues, together with systems having catechol and selected alkyl amines (unbound to catechol), we showed that the covalent linkage between the catechol and the amine via an alkyl chain is not required to show the adhesive property; however, this covalent link is crucial to achieve the impressive coating property of dopamine and its analogs. Our findings offer new insights in designing mussel-inspired materials for future BTE application, and further mechanistic understanding of the polymerization of dopamine and these new dopamine analogues.