Controlled delivery of recombinant human bone morphogenetic protein-2 by using glucose-sensitive core–shell nanofibers to repair the mandible defects in diabetic rats

The repair of mandible defects in diabetics has remained a challenge for a relatively long period. Bone tissue engineering scaffolds combined with controlled drug delivery systems can be considered as a promising strategy to resolve this problem. In this study, a novel glucose-sensitive scaffold composed of core-shell nanofibers with glucose oxidase immobilization was fabricated and characterized. In particular, polyethylene oxide encapsulating recombinant human bone morphogenetic protein-2 (rhBMP-2) formed the fiber's inner core layer and crosslinked polyvinyl alcohol mixed with N-(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride simultaneously formed the outer shell layer. The results prove that this scaffold yielded reliable glucose sensitivity performance, which implies that it can serve as a valve to control rhBMP-2 release in real time in response to changes in ambient glucose concentrations. In addition, a cell culture study revealed that this scaffold could effectively promote proliferation and osteogenic differentiation capacity of bone mesenchymal stem cells under hyperglycemic conditions. Finally, in vivo results further demonstrated that this material induced the optimal effect to promote the mandible regeneration in diabetic rats. In general, this glucose-sensitive scaffold provides a novel and potential therapeutic method for diabetics with mandible defects.