Simvastatin acid loaded material based on osmotic principle for bone regeneration: A sustainable release approach

Simvastatin, a traditionally recognized lipid-lowering medication, has emerged as a potent osteoinductive agent with significant potential in bone tissue engineering and regenerative medicine. Its advantages include multi-pathways enhancement of bone healing, potential application in special populations with osteoporosis (e.g., the elderly and pregnant women), high safety profile, and low cost. However, the clinical translation of simvastatin for bone regeneration has been challenged by its poor aqueous solubility, limited bioavailability when administered orally, and potential systemic side effects at higher doses. In this study, an osmotic pump system was developed as an innovative localized delivery carrier for simvastatin acid-loaded material, which could maintain therapeutic drug concentrations at the defect site for extended periods while minimizing systemic exposure. The approach mitigated the local inflammatory response caused by the burst release of simvastatin acid and enhanced the osteogenesis effect both in vitro and in vivo. This study represented the first application that loaded drugs with biomaterials through osmotic pump principle which is applicable to most materials loaded with water-soluble drugs, broadening the range of loadable drugs and their clinical application scope.