Injectable, in situ polymerizable, biodegradable scaffolds based on poly(propylene fumarate) for guided bone regeneration
Peter, Susan Jill
Mikos, Antonios G.
Doctor of Philosophy
Poly(propylene fumarate) (PPF) was developed as a scaffold to guide bone regeneration. Synthesis of this material via refined reaction pathways led to increased purity and higher molecular weights of this unsaturated, linear polyester. Due to its unsaturated nature, PPF can be formulated as an injectable composite through the incorporation of a vinyl monomer (N-vinyl pyrrolidinone), a leachable porogen (sodium chloride), and a particulate phase ($\beta$-tricalcium phosphate). Variations in this formulation led to the development of a material that can cure in situ at body temperature, resulting in a scaffold with mechanical properties equivalent to human trabecular bone. The composite formulation was altered to determine its effect on the time course of degradation under both in vitro and in vivo conditions. Inflammatory response upon subcutaneous implantation was monitored during in vivo degradation, with all composite formulations eliciting a mild initial inflammatory response followed by thin fibrous encapsulation. Marrow stromal cells were used to develop a model for in vitro bone formation. Osteogenic supplements were added early in the culture time frame to optimize the proliferation of these cells, as well as their differentiation into osteoblasts. PPF/$\beta$-tricalcium phosphate composites provided an osteoconductive surface for the proliferation and differentiation of marrow-derived cells. Additionally, delivery of growth factors to induce bone regeneration was investigated by incorporating transforming growth factor beta-1 into biodegradable microspheres. Increased proliferation and osteoblastic differentiation of marrow-derived cells was observed when they were maintained in the presence of the growth factor-loaded microparticles.
Biomedical engineering; Chemical engineering; Pharmaceutical sciences