Synergistic Effects of SDF-1α and BMP-2 Delivery from Proteolytically Degradable Hyaluronic Acid Hydrogels for Bone Repair

In order to achieve adequate bone repair, bone morphogenetic protein-2 (BMP-2) is typically delivered in large, non-physiological doses and can result in significant adverse side effects.[1] To reduce the amount of BMP-2 necessary for bone formation, we delivered another molecule, stromal cell derived factor-1α (SDF-1α), which is involved in stem cell recruitment[2,3] in combination with BMP-2. An engineered hyaluronic acid (HA) hydrogel that degrades via matrix metalloproteinases (MMPs) was used to deliver both molecules and release was mediated by protease level. A critical-sized calvarial defect model was used to assess biomolecule delivery on bone formation. The treatment group with combined SDF-1α and BMP-2 hydrogel delivery showed significantly higher bone formation when compared to hydrogels loaded with the same BMP-2 or SDF-1α concentration alone and was comparable to BMP-2 at an order of magnitude higher concentration, suggesting that the combined delivery of both biomolecules synergistically improves osteogenesis.