Development of Novel Photopolymerizable Hyaluronic Acid/Heparin-Based Hydrogel Scaffolds with a Controlled Release of Growth Factors for Enhanced Bone Regeneration

Abstract

In this study, the effect of novel BMP-2-loaded photo-cured hydrogels on in vitro and in vivo osteogenesis were explored. The well-defined HA-heparin hydrogel was prepared by a photopolymerization of aminoethyl methacrylate (AEMA) grafted hyaluronic acid (HA) and AEMA-grafted heparin. Subsequently, the resulting hydrogels contained BMP-2 at different concentrations. First, a series of BMP-2-loaded hydrogels were characterized to determine their mechanical properties and release profiles. The results from rheology, swelling ratio, and release kinetics suggest that BMP-2 contained HA-g-Hhep gel (B/HA-g-Hhep gel) had sustained release during 4 weeks with minimal initial burst. Furthermore, the released BMP-2 maintained its biological activity. MTT and live/dead assays showed that the B/HA-g-Hhep gel had good biocompatibility to be used as a scaffold for bone regeneration. In vivo studies of B/HA-g-Hhep gel exhibited significantly enhanced osteogenesis, compared with other types of HA-heparin hydrogels. These excellent results indicated that B/HA-g-Hhep gel has a great potential for a controlled release of growth factor, leading to a good bone regeneration.