Sustained and Localized In Vitro Release of BMP-2/7 RANKL and Tetracycline from FlexBone an Elastomeric Osteoconductive Bone Substitute

摘要

This study tests the hypothesis that synthetic composites containing a high percentage of osteoconductive biominerals well-integrated with a hydrophilic polymer matrix can be engineered to provide both the structural and biochemical framework of a viable synthetic bone substitute. FlexBone, an elastic hydrogel-mineral composite exhibiting excellent structural integration was prepared by crosslinking pHEMA hydrogel in the presence of 25wt% nanocrystalline hydroxyapatite and 25wt% tricalcium phosphate. Biologically active factors tetracycline, BMP-2/7 and RANKL that stimulate bone formation and remodeling were encapsulated into FlexBone during polymerization or via post-polymerization adsorption. SEM and DMA analyses showed that the encapsulation of tetracycline (5.0wt%) did not compromise the structural integrity and compressive behavior of FlexBone, which could withstand repetitive megapascal-compressive loadings and be securely press-fitted into critical femoral defects. Dose-dependent, sustained in vitro release of tetracycline from FlexBone was characterized by spectroscopy and bacterial inhibition. A single dose of 40-ng-BMP-2/7 or 10-ng-RANKL pre-encapsulated with 50-mg-FlexBone, released over 1 week, was able to locally induce osteogenic differentiation of myoblast C2C12 cells and osteoclastogenesis of macrophage RAW264.7 cells, respectively. With a bone-like structural composition, useful surgical handling characteristics and tunable biochemical microenvironment, FlexBone provides an exciting opportunity for the treatment of hard-to-heal skeletal defects with minimal systemic side effects.