Polyphenols-functionalized hydroxyapatite nanocomposites/carbohydrazide grafted gelatin/oxidized dextran adhesive hydrogel with osteogenic and angiogenic activity for bone defect repair.

Abstract

Current bone adhesives face critical limitations in osseointegration and vascularization, severely restricting their efficacy in bone defect repair. To address these challenges, we report an injectable adhesive hydrogel synergizing tannic acid-functionalized hydroxyapatite nanocomposites and deferoxamine to remodel microenvironment for bone defect repair. Structural characterization via scanning electron microscope confirmed a porous network with homogeneous nanocomposites dispersion. Meanwhile, rheological studies revealed shear-thinning injectability and self-healing capability. Besides, the hydrogel exhibited interfacial adhesion and cytocompatibility, supporting >90% cell viability with enhanced migration and proliferation. Notably, in vitro studies demonstrated multifunctionality: the hydrogel enhanced angiogenic activity through increased endothelial tubule formation. Moreover, the hydrogel upregulated osteogenic differentiation via elevated expression of runt-related transcription factor 2, osteocalcin, and alkaline phosphatase. In a femoral defect rat model, micro-CT analysis revealed greater new bone volume and superior trabecular thickness and trabecular number in hydrogel-treated groups at 8 weeks. Furthermore, histological examination including H&E and Masson staining demonstrated that the hydrogel contributed to newly forming bone and mature collagen deposition. Immunohistochemical evaluation confirmed enhanced neovascularization in vivo. Hence, this work developed an injectable adhesive hydrogel as a promising bone adhesive for bone defect repair through material-mediated microenvironment with synergistic multifunctionality in osteogenesis and angiogenesis.