Google
Yelp
Facebook
Twitter
ChEnected
342945 Simultaneous Delivery of SDF-1α 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.
Maleimide-modified HA (MaHA) dissolved in phosphate buffered saline (PBS) was crosslinked with a matrix metalloprotease (MMP) sensitive peptide according to a Michael Type additional reaction, allowing for protease-mediated hydrogel degradation and growth factor release. MaHA hydrogels loaded with either 100 ng/scaffold of SDF-1α or BMP2 were degraded in 10, 2, or 1 U/ml type II collagenase (non-specific MMP degradation) at 37°C and compared to degradation in PBS. In the presence of MMPs, hydrogel degradation and growth factor release was controlled as a function of both collagenase concentration and hydrogel formulation. At high collagenase concentrations (10 U/ml) hydrogel degradation occurred rapidly overnight. At lower concentrations, hydrogel degradation occurred slower with growth factor release over a period of approximately two weeks in 1 U/ml collagenase. Minimal hydrogel degradation and growth factor release were observed in the absence of MMPs. The in vitro chemotactic activity of SDF-1α released from MaHA hydrogels was also determined. Current work is evaluating the simultaneous delivery of SDF-1α and BMP2 in an in vivo cranial defect rat model on BMP-induced osteogenesis.