Polymer-Based Approaches to Bone Tissue Repair and Regeneration
Kasper, F. Kurtis
Doctor of Philosophy
The loss or damage of bone tissue due to trauma or surgical resection remains a significant clinical challenge. Limitations associated with the current gold standard of care, autografting, include donor site morbidity and an inherent lack of availability; thus prompting the need for alternative therapies and materials. Poly(propylene fumarate) (PPF) is a synthetic polymer that has previously been explored for bone tissue engineering applications. In this work, the properties of various formulations of PPF were optimized for specific clinical applications. Initially, a composite scaffold comprised of a solid PPF intramedullary rod and porous sleeve was evaluated in a segmental rat femoral defect model. The presence of the scaffold was able to increase the mechanical stability of the defect but also may have acted as a physical barrier to bone formation. In accordance with these results and through interactions with clinical collaborators, subsequent formulations of PPF targeted bony fractures and defects of the mandible. Key formulation parameters of PPF were varied in order to develop constructs with handling and mechanical properties suitable for mandibular fracture repair applications. Further consideration of the clinical relevancy of PPF-based materials led to the development of PPF as an analog to FDA-approved poly(methyl methacrylate) (PMMA)-based bone cement products. It was found that introducing crosslinked PPF particles to a liquid PPF phase could reduce the maximum crosslinking temperature as well as produce setting and handling characteristics comparable to that of current PMMA-based products. Lastly, as the development of biomaterials must continually adapt to fulfill changing clinical needs, a clinically focused project was performed in which porous PMMA-based implants were fabricated, characterized, and implanted under physician direction. Although successful, the limitations of PMMA including its non-degradable nature and the potential for bacterial contamination led to the development of degradable, porous PPF constructs capable of local antibiotic delivery for craniofacial applications. Properties of interest including degradation, porosity change over time, and antibiotic release kinetics were found to be suitable for craniofacial applications. The studies described here showcase the range of clinical applications that may be fulfilled by PPF-based materials.
Tissue engineering; Poly(propylene fumarate)