Abstract
Non-union bone fractures present a complex clinical challenge where bone tissue is unable to heal without intervention. This clinical problem promoted wide-spread interest in developing enhanced tissue healing through the use of cells, signals, and scaffolds via tissue engineering. This work focused on developing a tissue engineered scaffold for bone tissue healing and regeneration by incorporating biomolecules into a polyampholyte polymer system. In the first part of this work, the formulation of a polyampholyte polymer system was optimized for enhanced biocompatibility. Characterization of qualitative nonfouling and conjugation capacity were evaluated, as well as quantitative cell adhesion, proliferation, and viability. Additionally, the polymer system performance was enhanced with a novel zwitterionic crosslinker to improve its potential future in vivo applications. The zwitterionic cross-linked hydrogel exhibited excellent nonfouling properties along with increased cell adhesion and viability to conjugated fibrinogen compared to a control hydrogel.
The second part of this work then investigates the impact of calcium exposure on the bioactivity of bovine serum albumin (BSA). Calcium modified BSA improved overall preosteoblast cell adhesion. Additionally, as the calcium exposure increased, the primary cell binding pathways transitioned. Potential implications of this will be discussed.
Finally, the last part of this dissertation focuses on the delivery of calcium modified, bioactive BSA via a polyampholyte polymer hydrogel. An optimal calcium exposure concentration promoted strong levels of adhesion and viability for preosteoblast cells. Together, these results demonstrate great potential for a novel bone tissue engineered strategy based on the delivery of bioactive albumin from a biocompatible polyampholyte hydrogel.