"Biomaterial Strategies for Improved Bone Healing and Immunomodulation in BMP-2 Delivery"

Advisor:  Robert E. Guldberg, Ph.D. (Georgia Institute of Technology)

Committee:
Edward A. Botchwey, PhD. (Georgia Institute of Technology)
Andrés J. García, Ph.D. (Georgia Institute of Technology)
Johnna S. Temenoff, Ph.D. (Georgia Institute of Technology)
Lisa Tran, M.D. (Emory University)

Musculoskeletal injuries account for two-thirds of all injuries that occur in the United States annually, and among these injuries, large bone defects are particularly challenging to repair. Although bone morphogenetic protein-2 (BMP-2) delivered on a resorbable collagen sponge has shown clinical success in long bone healing, complications associated with the empirical use of supraphysiological doses of BMP-2, including heterotopic mineralization and inflammation, necessitate the development of a biomaterial carrier that localizes growth factors to the site of injury. In the development of bone tissue engineering strategies, another critical design parameter is the timing of delivery vehicle degradation, since bone regeneration may be impeded by the presence of residual biomaterials at the injury site. Further, bioactive, naturally derived extracellular matrix (ECM) products with pro-healing and immunomodulatory properties are attractive therapeutics with rapid translatability that may function to augment bone regeneration.

The goal of this work is to engineer a hybrid degradable biomaterial system for BMP-2 delivery that promotes bone formation and limits complications in the surrounding soft tissue. Using a critically sized rat segmental bone defect model, we will (i) evaluate the effects of partial oxidation of RGD alginate hydrogels on BMP-2 release and bone regeneration, (ii) elucidate the spatiotemporal effects of high-dose BMP-2 as a function of delivery vehicle on inflammation and bone healing, and (iii) investigate the ability of amnion-derived ECM to modulate inflammation and enhance bone regeneration. Modification of the delivery vehicle to allow for prolonged growth factor availability may increase the regenerative potential of low-dose BMP-2. Additionally, biomaterials with immunomodulatory properties may help minimize adverse side effects associated with high-dose BMP-2 delivery, while harnessing the healing efficacy of BMP-2 for bone tissue engineering applications.