ZIF-8-Modified Multifunctional Bone-Adhesive Hydrogels Promoting Angiogenesis and Osteogenesis for Bone Regeneration.

Abstract

Designing bone adhesives with adhesiveness, antideformation, biocompatibility, and biofunctional effects has great practical significance for bone defect reconstructive treatment, especially for bone graft repair surgery. Here, we designed zeolitic imidazolate framework-8 nanoparticle (ZIF-8 NP)-modified catechol-chitosan (CA-CS) multifunctional hydrogels (CA-CS/Z) to stabilize the bone graft environment, ensure blood supply, promote osteogenic differentiation, and accelerate bone reconstruction. Characterizations confirmed the successful synthesis of CA-CS/Z hydrogels. Hydrogels exhibited advanced rheological properties, reliable mechanical strength, and excellent adhesion for clinical applications. Based on excellent biocompatibility, it could enhance paracrine of the vascular endothelial growth factor (VEGF) in rat bone marrow mesenchymal stem cells (rBMSCs) to ensure blood supply reconstruction in bone defect areas. Furthermore, the ZIF-8 NPs released from the hydrogels could also up-regulate the production and secretion of alkaline phosphatase, collagen 1, and osteocalcin, promoting the osteogenic differentiation of rBMSCs. In addition, the antibacterial properties of CA-CS/Z could also be observed. In vivo experiments further provided a powerful proof that CA-CS/Z promoted vascularized osteogenesis in wound areas by stabilizing bone graft materials and greatly accelerated the speed and healing of bone reconstruction. These results indicate the promising potential of CA-CS/Z hydrogels with promoting implantation stability, angiogenesis, and osteogenesis for bone regeneration applications.