Synthesis of poly(lactide)-based amphiphilic block copolymers and hydroxyapatite nanoparticles for bone tissue engineering applications

Abstract

Due to the drawbacks associated with traditionally used bone substitutes, such as autografts and allografts, the field of tissue engineering, regenerative medicine and biomaterials science has recently come to the forefront with new strategies for bone repair and de novo tissue formation. Current research has focused on employing bionanocomposites composed of polymers, such as poly(lactide) (PLA), and inorganic calcium phosphate ceramics, such as hydroxyapatite (HA). These hybrid materials benefit from combining biodegradability, biocompatibility, bioactivity, and other advantageous scaffold properties to better mimic biological and structural characteristics of native bone. With this in mind, the work presented in this dissertation focuses on the synthesis of well-controlled PLA homopolymers, as well as amphiphilic block copolymers. This was achieved via the ring opening polymerization (ROP) of lactide using an organocatalyst and the successful combination of ROP of lactide and the reversible addition-fragmentation chain transfer (RAFT) polymerization of poly(ethylene glycol) ethyl ether methacrylate (PEGEEMA) using a novel heterofunctional initiator/chain transfer agent (inifer). Comprehensive kinetics studies also provided valuable insights into the factors influencing the synthesis of well-defined block copolymers. These polymers were then successfully processed into fibrous scaffolds using electrospinning techniques and the different parameters affecting fiber formation and morphology were investigated. In addition, the prepared scaffolds were evaluated in terms of overall hydrophilicity, in vitro performance, and biodegradation behavior. Furthermore, a hydrothermal synthesis approach was employed to produce well-defined HA nanoparticles with tunable sizes that can be used in biomimetic nanocomposite scaffolds. Lastly, the surface modification of the HA nanoparticles was investigated via a grafting-from approach using the ROP of lactide, as well as via the use of a poly(dopamine) coating. Overall, the results presented in this dissertation provide important mechanistic insights into the successful synthesis of well-controlled amphiphilic block copolymers and also contribute to developing facile methods to prepare biomimetic HA nanoparticles and biodegradable fiber scaffolds. The findings also further highlight the importance of polymer and nanoparticle-containing bionanocomposite scaffolds, which have the potential to greatly improve the treatment of bone defects and bone loss.