Thermoresponsive dual-network chitosan-based hydrogels with demineralized bone matrix for controlled release of rhBMP9 in the treatment of femoral head osteonecrosis.

Abstract

In an effort to mitigate or reverse the pathological progression of early-stage osteonecrosis of the femoral head (ONFH), this study employed a promising strategy that involves the sustained delivery of osteogenic factors to augment core decompression, facilitated by the use of composite hydrogels. Specifically, a hydrogel was synthesized by blending chitosan, Pluronic F-127, and tripolyphosphate, utilizing both ionic bonding and copolymer micelle cross-linking techniques. This hydrogel demonstrated exceptional biocompatibility, temperature responsiveness, pH-dependent biodegradation, and controlled release properties. The average pore diameter of the optimal hydrogel expanded to 45 μm, accompanied by zeta potentials of +34.72 ± 4.13 mV. The loading efficiency notably surpassed 90 %, while the sustained release of recombinant human bone morphogenetic proteins 9 (rhBMP9) was observed to last over 25 days at pH = 6.0 and over 36 days at pH = 7.4. This chitosan-based hydrogel, which sustained rhBMP9 release, significantly enhanced the proliferation and migration of bone marrow mesenchymal stem cells and human umbilical vein endothelial cells and promoted osteogenesis and angiogenesis both in vitro and in vivo. Collectively, our study presents an rhBMP9-loaded chitosan-based composite hydrogel system that offers innovative avenues for the research and clinical application of advanced biomaterials in the treatment of early ONFH.