Date of Award
Doctor of Philosophy
Comparative and Experimental Medicine
Madhu Dhar, David Anderson, Jack Gotcher, Shawn Bourdo, Alex Biris
The field of bone tissue engineering features a wide variety of biomaterials designed to facilitate repair and restoration of injured bone tissue. Due to the complex nature of bone, these graft materials face unique challenges in accommodating this highly dynamic environment in which internal structures are being constantly remodeled via osteoblastic and osteoclastic functions. Therefore, effective graft designs must incorporate compositional elements that are capable of promoting and facilitating such activity to permit successful integration with native tissue. These osteobiologic characteristics, including osteo-conduction, osteo-induction, and osseo-integration, are key factors in determining a materials osteogenic capacity and its potential as a bone graft technology. The comprised studies focus on the development and biological assessment of a construct that incorporates osteobiologic components, nano-hydroxyapatite (nHA) and decellularized bone particles (DBPs), within a polymeric binder to form osteogenic matrices for enhancing bone repair. A battery of in vitro and in vivo assessments of this osteogenic platform were carried out at various stages of the development process to characterize the impact of this biomaterial on multiple cell lines, both immortalized and naïve, as well as in different rodent bone defect models, in both long bone and oromaxillofacial applications. Promising in vitro and in vivo data at early stages paved the way for more extensive testing, in particular the examination of target proteins expressed in treated tissue, through immunohistochemical techniques, and of the molecular impact of the graft material, using both metabolomic and transcriptomics. Positive detection of key proteins associated with osteogenic and cell attachment functions further supported evidence that scaffolds served as effective matrices for cellular migration and subsequent osteo-differentiation. Additionally, the development of potential pathways of effect for these constructs on exposed naïve cells provided key targets for future studies, which may elucidate the precise mechanisms responsible for the observed biological responses. Furthermore, this multi-omics methodology presents a powerful tool for the evaluation of new graft technologies, promoting the potential of intelligent biomaterial design for specific applications.
Bow, Austin, "Novel Osteobiologics for Bone Tissue Engineering. " PhD diss., University of Tennessee, 2019.