Angiogenesis–osteogenesis coupling and immunomodulatory CGRP@nano MOF-loaded CMCS/GelMA hydrogel for bone regeneration†

The management of bone defects poses a significant challenge for clinicians, necessitating effective strategies to regulate immune inflammation, angiogenesis, and osteogenic differentiation for successful bone regeneration. In this study, we developed a novel hydrogel composed of carboxymethyl chitosan (CMCS) and gelatin methacryloyl (GelMA) designed for the sustained release of the bioactive component calcitonin gene-related peptide (CGRP) and zeolitic imidazolate framework-8 (ZIF-8). CGRP was initially encapsulated within ZIF-8 and subsequently integrated into the CMCS/GelMA hydrogel matrix. In vitro evaluations revealed that the hydrogel exhibited exceptional biocompatibility and antimicrobial properties, effectively promoting osteogenesis and angiogenesis while modulating M2 macrophage polarization. Furthermore, in vivo assessments indicated that the CGRP@MOF/CG hydrogel significantly regulated the local immune microenvironment and accelerated the healing of cranial defects in rat models. This study provides valuable references for the design and fabrication of multifunctional materials for enhancing bone regeneration.