Calcium phosphate bone cements with α-ketoglutarate polyester microspheres promote osteoporotic bone defect repair†

Excessive oxidative stress and inflammation are prevalent in osteoporotic bone defects, significantly impairing the efficacy of bone regeneration in such defects. Calcium phosphate bone cements (CPC) are a commonly employed material for repairing bone defects. However, the slow rate of osteogenic mineralization and biodegradation presents a significant challenge in meeting the requirements of osteoporotic bone treatment. In this study, α-ketoglutarate (α-KG) polyester microspheres were synthesized from α-KG. By introducing different mass ratios of α-KG polyester microspheres, we constructed CPC with α-KG polyester microspheres (CPC/α-KG) that exhibited an improved microenvironment, enhanced osteogenic differentiation, and increased biomineralization. The incorporation of α-KG polyester microspheres was instrumental in enhancing the physicochemical attributes, biodegradability, biocompatibility, osteogenic differentiation potential, and biomineralization of α-KG. Mechanistically, the CPC/α-KG improves the osteogenic microenvironment by inhibiting the inflammatory response and reducing oxidative stress through the PI3K/AKT signaling pathway. Notably, the addition of 10 wt% α-KG polyester microspheres resulted in the optimal osteogenic capacity for CPC/α-KG. In conclusion, the modified α-KG composites show potential as effective candidates for bone defect repair and regeneration.