Three-dimensional bioglass-nanoclay scaffold with localized controlled release of 4-octyl itaconate promotes bone regeneration in osteoporotic bone defects

Osteoporotic bone defect repair is a complex physiological process occurring under pathological conditions, which primarily involves the inhibition of bone resorption and the promotion of bone formation. In recent years, composite scaffolds for localized drug delivery have been developed to enhance the healing of osteoporotic bone defects, emerging as a promising yet challenging area of research and clinical application. In the present study, we fabricated a composite scaffold (BG-XLS/ZIF8@4-OI) enabling the localized and controlled release of 4-octyl itaconate (4-OI), a cell-permeable itaconate derivative, for the treatment of osteoporotic bone defects. The scaffold exhibited an interconnected porous structure with pore sizes ranging from 100 to 500 μm, favorable mechanical strength, and sustained release of 4-OI. In vitro, MC3T3-E1 cells demonstrated strong adhesion and proliferation on the composite scaffold. Additional in vitro experiments confirmed that scaffold extracts were non-toxic to cells, effectively inhibited osteoclast formation, and promoted osteoblast proliferation and differentiation. In vivo, the BG-XLS/ZIF8@4-OI scaffold effectively promoted local bone regeneration within the defect region in a rat osteoporotic cranial defect model. In conclusion, these findings indicate that the BG-XLS/ZIF8@4-OI scaffold exhibited good biocompatibility and safety for osteoporotic cranial bone defect repair in rats, improved the local osteoporotic microenvironment, and promoted bone formation, holding immense potential to enhance osteoporotic bone defect repair.