Polymer Chemistry

Biography

Biography: Oommen Varghese

Abstract

Designing injectable gels that mimic the natural extracellular matrix (ECM) has been of great interest in the field of regenerative medicine. We have previously demonstrated that hyaluronic acid (HA) hydrogel having hydrazone crosslinkages could be used for efficient delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and form bone in vivo within 6 weeks when injected below the rat periostium. Though rhBMP-2 is very potent for inducing bone formation, recently, extensive debate has taken place on the clinical use of rhBMP-2 since several complications in patients has been observed. This is mainly due to supraphysiological dose that is clinically used since the collagen-based BMP-2 carrier is inefficient and does not stabilize rhBMP-2 in vivo. We have devised a new strategy to engineer hydrazone crosslinked HA hydrogel such that it differentially interact with rhBMP-2 and provide different release kinetics of the bioactive protein. In order to understand the binding affinity between HA modification and the heterodimer structure of rhBMP-2, we performed computational analysis by performing molecular docking followed molecular dynamics experiments. The results of the computational analysis clearly indicated that electrostatic and Vander Waal’s interactions play a predominant role in stabilizing rhBMP-2 and control its release. To further understand the significance of protein release on bone formation, we performed in vivo bone induction experiments in a rat ectopic model. The in vitro release experiments corroborated very well with the in vivo experiments, which clearly indicate that improving BMP-2 interactions with HA has major impact in stem cell recruitment and bone induction in vivo. Such a biomaterial design strategy could also be easily adapted to deliver other growth factors for different biomedical applications.