Vitamin D3-loaded calcium citrate/calcium sulfate composite cement with enhanced physicochemical properties, drug release, and cytocompatibility

Vitamin D3 (VD3), an important regulator of calcium and phosphate ion concentrations in blood serum, participates in bone formation by promoting calcium and citrate deposition at defect sites while further stimulating bone calcification and osteoblast function. In this study, VD3-loaded calcium sulfate (VD3/CS) and calcium citrate/calcium sulfate (VD3/CC/CS) cements were successfully fabricated for the first time. The incorporation of VD3 into the cements did not alter their structures or physicochemical properties. Additionally, compared with the VD3/CS cement, the VD3/CC/CS composite cement showed higher mechanical strength (28.87 MPa), better injectability (94.48%), and more appropriate setting time (23.7 min). Depending on the method by which the loaded VD3 was adsorbed, both VD3/CS and VD3/CC/CS cements could achieve sustained drug release. However, due to their different compositions, VD3/CS cement samples, owing to the dissolution of their matrix, showed faster VD3 release rates, while VD3/CC/CS composite cement samples showed more controlled VD3 release rates, owing to the presence of a physical barrier created by calcium citrate. The VD3/CC/CS composite cement samples also demonstrated excellent bioactivity at cellular level, indicating that the VD3/CC/CS composite cement might be beneficial for the localised treatment of bone defects, especially osteoporotic bone.