3D bioprinted biomimetic MOF-functionalized hydrogel scaffolds for bone regeneration: Synergistic osteogenesis and osteoimmunomodulation

Critical-size bone defects remain a significant clinical challenge. The lack of endogenous stem cells with osteogenic differentiation potential in the defect area, combined with the inflammatory responses induced by scaffold implantation, highlights the need for biomaterials that can deliver stem cells and possess inflammatory regulation properties. In this study, we developed a 3D bioprinted gelatin methacrylate (GelMA) hydrogel scaffold modified with luteolin-loaded ZIF-8 (LUT@ZIF-8) nanoparticles, designed to deliver bone marrow mesenchymal stem cells (BMSCs) to the defect site and release bioactive components that promote osteogenesis and modulate the immune microenvironment. The LUT@ZIF-8/GelMA hydrogel scaffolds demonstrated excellent physical properties and biocompatibility. The sustained release of luteolin and zinc ions from the LUT@ZIF-8 nanoparticles conferred antibacterial, osteoinductive, and inflammatory regulation effects. The immune microenvironment modulated by LUT@ZIF-8/GelMA hydrogel scaffolds facilitated osteogenic differentiation of BMSCs. Furthermore, <i>in vivo</i> experiments confirmed the osteogenic and inflammatory regulation capabilities of the LUT@ZIF-8/GelMA hydrogel scaffolds. In conclusion, the 3D bioprinted LUT@ZIF-8/GelMA hydrogel scaffolds exhibit osteoimmunomodulatory properties, presenting a promising strategy for the treatment of bone defects.