Date of Award
Doctor of Philosophy
Roberto S. Benson, Kevin M. Kit, Bin Zhao
This dissertation presents novel biodegradable and photo-crosslinkable building blocks to achieve polymer networks with controlled surface chemistry, stiffness, and topographical features for investigating cell-material interactions and targeting hard and soft tissue engineering applications. Chapter I reviews the recent progress in polymeric gel systems and how their physical properties can be tailored to regulate cell functions and satisfy the clinical needs. Chapter II presents a facile method to synthesize photo-crosslinkable poly(epsilon-caprolactone) acrylates (PCLAs) and reveal tunable cell responses to photo-crosslinked PCLAs. Chapter III investigates the mechanism of colorization in preparing crosslinkable polymers by reacting hydroxyl-containing polymers with unsaturated anhydrides or acyl chlorides in the presence of triethylamine. Chapter IV describes a systematic investigation on regulating materials properties and cell behavior using hybrid networks composed of amorphous poly(propylene fumarate) (PPF) and three PCLAs with variance in crystallinity and melting temperature. Schwann cell precursor line (SpL201) and pre-osteoblastic MC3T3-E1 responses to these polymer networks such as cell adhesion, spreading, and proliferation demonstrated non-monotonic dependence on the network composition. Chapter V synthesizes a series of novel injectable and photo-crosslinkable PPF-co-polyhedral oligomeric silsesquioxane (POSS) copolymers via two-step polycondensation to improve both stiffness and toughness and promote biological performance of bone tissue engineering scaffolds. Chapter VI photo-crosslinks PPF with methoxy poly(ethylene glycol) monoacrylate (mPEGA) to improve the hydrophilicity and wettability of PPF and MC3T3-E1 cell functions. Chapter VII investigates the role of exposed hydroxyapatite (HA) nanoparticles in influencing surface characteristics and MC3T3-E1 cell behavior on crosslinked PCLA/HA nanocomposites. Chapter VIII presents a method of tuning surface chemistry and nerve cell behavior by photo-crosslinking mPEGA with a hydrophobic, semicrystalline PCLA at various compositions. This approach lays the foundation for fabricating heterogeneous nerve conduits with a compositional gradient along the wall thickness. Chapter IX demonstrates the role of mechanical properties and surface features on nerve cell behavior using two photo-crosslinked poly(epsilon-caprolactone) triacrylates with distinct mechanical properties and parallel microgrooves with different dimensions. Chapter X and XII develop a novel photopolymerizable poly(L-lysine) and uses it to modify polyethylene glycol diacrylate hydrogels for creating a better, permissive nerve cell carrier that promoted cell functions for treatment of nerve injuries.
Cai, Lei, "Modulation of Bone and Nerve Cell Behavior Using Biodegradable Polymer Networks. " PhD diss., University of Tennessee, 2012.