Nano SIM@ZIF-8 modified injectable High-intensity biohydrogel with bidirectional regulation of osteogenesis and Anti-adipogenesis for bone repair

Hyperlipidemia negatively affects osteogenesis, thereby impairing bone healing. However, few biomaterials have been developed for bone tissue engineering to solve this problem. Herein, the preparation of specific biomaterials that can promote osteogenesis and suppress adipogenesis holds great promise for reconstructive bone defect treatment. In this study, we propose the construction of a nano simvastatin-laden zeolitic imidazolate framework-8 (nano [email protected]) modified injectable high-intensity biohydrogel, composed of poly (ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA) to form nano [email protected]/PEGDA/SA (defined as nSZPS), which can stimulate osteogenic differentiation and inhibit adipogenic differentiation. The characterization and drug loading efficiency of the nanoparticles were examined to confirm the successful synthesis of nano [email protected] Within the PEGDA/SA delivery platform, nSZPS showed excellent injectability and mechanical strength through rheological and mechanical tests. Moreover, owing to the sustained release of SIM and bioactive Zn ions, nSZPS not only possessed excellent biocompatibility but also significantly enhanced the osteogenic differentiation ability and inhibited the adipogenic efficacy of BMSCs in vitro. Furthermore, nSZPS showed excellent osseointegration and lipid-lowering abilities in healing bone defects of hyperlipidemic rats by decreasing PPARγ expression and increasing RUNX2 expression in vivo. In addition, the bidirectional regulatory mechanisms of nSZPS in bone defects may be closely related to the mutual regulation of the PPARγ and Wnt/β-CATENIN pathways. In summary, this nano [email protected] modified injectable high-intensity biohydrogel might be a promising strategy for complex bone regeneration, especially in hyperlipidemic microenvironments.