(42e) Simultaneous Delivery of SDF-1? and BMP2 Using Enzymatically Degradable Hydrogels for Improved Osteogenesis

The use of bone morphogenic proteins (BMPs) show promise in therapies for improving bone regeneration; however, the high supraphysiological concentrations required for desired osteoinductive effects, costs, and patient variability have prevented BMP-based therapeutics from being fully realized. In this work, a matrix metalloprotease (MMP)-sensitive hyaluronic acid (HA)-based hydrogel was used for the delivery of both stromal cell-derived factor-1 alpha (SDF-1α) and BMP2 towards improving BMP-induced osteogenesis. SDF-1α plays an important role in stem cell trafficking and HA hydrogels are known to increase extracellular matrix production. A modified Boyden chamber assay was used to determine the in vitro chemotactic activities of SDF-1α and HA using human mesenchymal stem cells (hMSCs). A monoclonal antibody to CD44 (for HA specific blocking) and a CXCR4 antagonist (for SDF-1α specific blocking) were used to assess the individual effects of both SDF-1α and HA on cell migration. SDF-1a significantly increased hMSC chemotaxis, approximately 2-fold, when compared to chemotaxis without SDF-1a. Interestingly, HA also showed evidence of increasing chemotaxis.