Improvement of aqueous stability and anti-osteoporosis properties of Zn-MOF coatings on titanium implants by hydrophobic raloxifene

Endowed with superior tailorability and functionality, metal-organic frameworks (MOFs) have been exploited for their diverse applications in biomedicine. However, the instability of MOFs under an aqueous environment causes an accelerated degradation preventing their clinical applications and commercialization. To address this issue, studies have reported the incorporation of hydrophobic functional groups into MOF to enhance its stability. In this study, we aimed to fabricate a multifunctional coating on titanium implants by exploiting the synergy between Zn-based MOFs and raloxifene (Ral). We theorized that the integration of MOF and Ral will not only locally deliver the drug, but also take advantage of the hydrophobic functional group of Ral to enhance the stability of MOF in an aqueous environment. The release studies showed a sustained release of both Zn2+ and Ral for more than 14 d. In-depth in vitro investigations also verified that MOF/Ral coatings significantly enhanced the cell viability and osteogenic differentiation of osteoblasts, as well as decreasing the tartrate-resistant acid phosphatase activity and osteoclastic biomarker expressions. In addition, both micro-computed tomography and immunohistochemical analysis further confirmed the efficacy of MOF/Ral coatings in the formation of new bone within the femurs of osteoporotic rats. The feasibility of MOF/Ral coated titanium implants in inhibiting osteolysis and promoting osteogenesis has undoubtedly proved their clinical prospects in the treatment of osteoporotic bone injury.