Bgh/GelMA/CMCS hydrogel with bone MSC-EVs for lunate defect repair

PURPOSE: Kienböck disease, characterized by avascular necrosis of the lunate bone, remains difficult to treat. This study developed a 3D-printed Bgh/GelMA/CMCS (BGC) hydrogel scaffold loaded with bone mesenchymal stem cells (MSC-EVs) for lunate bone repair. METHOD: MSC-EVs were isolated using ultracentrifugation, and incorporated into BGC lunate-like scaffolds via 3D-printing. Scaffold properties, including surface morphology, biomechanical strength, degradation, and EV release, were investigated. Rabbit lunate defects were treated with these hydrogel scaffolds, and their structure and stability were evaluated. Inflammation, neovascularization, and bone generation were analyzed. RESULTS: The BGC hydrogel scaffold loaded with MSC-EVs maintained bioactivity with excellent biocompatibility and stability, releasing EVs slowly over a month. In vitro, EVs@BGC hydrogel promoted HUVEC and BMSC proliferation, migration, and tube formation. In vivo, the M1/M2 ratio and inflammatory factors decreased significantly one-week post-implantation, while CD31 and VEGF-positive cells increased at four weeks, and BMP2 and OPN-positive cells at eight weeks. HE staining and Masson's trichrome showed better bone generation in the EVs@BGC group. CONCLUSIONS: The EVs@BGC lunate-like hydrogel scaffold provides structural support and sustained MSC-EV release, reducing early inflammation and enhancing neovascularization and bone formation over time.