Synthetic Hydrogel Delivery of Growth Factors and Demineralized Bone Matrix for Bone Augmentation
Kinard, Lucas A.
Mikos, Antonios G.
Doctor of Philosophy
The overarching objective of this thesis was to investigate synthetic hydrogel delivery of growth factors and demineralized bone matrix (DBM) for bone augmentation. Our motivation rests on observed weaknesses of current clinical approaches to bone augmentation, which synthetic hydrogels hope to overcome based on non-invasive application, contouring, tunability, and drug delivery. First, we investigated the release of bone morphogenetic protein-2 (BMP-2) from gelatin microparticles. Hydrogel composites based on oligo(poly(ethylene glycol) fumarate) (OPF) were prepared to investigate the effect of gelatin amount, gelatin type, and BMP-2 loading phase on release. The most significant factor affecting the release of BMP-2 was the loading phase, whereby gelatin loading reduced the burst release and increased BMP-2 release during later phases. Our results indicated tunability of the physical properties and BMP-2 release kinetics of our hydrogel composites. Second, we developed a rat model for bone augmentation and investigated our BMP-2 delivery system in vivo. Our animal model achieved rigid immobilization of bilateral implants apposed to the parietal bone of the rat. The BMP-2 release profile was varied and compared to the implantation of a material control without BMP-2. The volume of bone augmentation did not vary between groups after 4 weeks largely due to insignificant hydrogel degradation. Altogether, a promising rat model of bone augmentation was established; however, refinement of the hydrogel composites was suggested. Lastly, we investigated OPF for the delivery of DBM for bone augmentation in a rat model. OPF constructs were designed and fabricated by varying the content of rat-derived DBM particles and using two DBM particle size ranges. The physical properties of the constructs and the bioactivity of the DBM were evaluated. Select formulations were evaluated in vivo compared to an empty control to investigate the effect of DBM dose and construct properties on bone augmentation. Overall, constructs with higher DBM content achieved the greatest volume of bone augmentation, exceeding lower DBM constructs and empty implants by 3-fold and 5-fold, respectively. We established that a synthetic, biodegradable hydrogel can function as a carrier for DBM, and that the volume of bone augmentation achieved by the constructs correlated directly to DBM dose.
Synthetic hydrogel; Drug delivery; Bone augmentation; Chemical engineering