Tunable Release of BMP-2 From Thiol-ene Click Hydrogels

Abstract

With over 6.3 million fractures that occur in the United States each year, autogenic and allogenic bone sources are becoming a dwindling resource. Bone Morphogenetic Protein-2 (BMP-2) has been shown to induce osteoblast differentiation, but uncontrolled release of these growth factors can cause potentially life threatening complications to occur. This issue provides motivation for the development of synthetic polymer based drug delivery systems, more specifically hydrogels, due to their tunability of the mesh size, rate of degradation, and ability to incorporate different growth factor-binding chemical moieties, such as bisphosphonates. Bisphosphonate is an affinity ligand that has been shown to electrostatically interact with BMP-2 and can be tethered into hydrogel matrices in order to non-covalently control release and maintain the bioactivity of the growth factor. In this study, we compare controlled release of osteogenic growth factor BMP-2 from tunable poly(ethylene glycol) hydrogels that were functionalized with varying amounts of the bisphosphonate sodium alendronate. By characterizing our hydrogel system through storage modulus and swelling ratio measurements and monitoring growth factor release rate through a rhBMP-2 specific ELISA assay, we found significant differences in release over a period of one week due to varying incorporation of bisphosphonate. These results indicate the need for further investigation to explore the release and tunability of our platform.