The development of novel multifunctional drug system 7,8-DHF@ZIF-8 and its potential application in bone defect healing

Abstract

Physical exercise has long been considered an essential regulator of bone formation. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is an important cytokine released during physical exercise to promote osteogenic differentiation and facilitate the bone defect healing process. In this study, we developed a multifunctional system 7,8-DHF@ZIF-8, which combines the superior osteogenesis and angiogenesis properties of ZIF-8 and the unique capability of 7,8-DHF to mimic the function of BDNF to compensate for the routine physical exercise missed during the bone defect period. Various material characterizations were performed to confirm the successful synthesis of 7,8-DHF@ZIF-8. Drug release experiments suggested that 7,8-DHF@ZIF-8 could achieve slow diffusive release under physiological conditions within seven days. In vitro cell experiments indicated that low concentrations of ZIF-8 and 7,8-DHF@ZIF-8 could significantly promote the proliferation of MC3T3-E1 cells. Moreover, as proved by RT-QPCR analysis, incorporating 7,8-DHF into ZIF-8 could further enhance osteogenesis and angiogenesis-related gene expression. Therefore, we believe that the multifunctional drug system 7,8-DHF@ZIF-8 should have promising applications to facilitate bone defect healing.

Keywords: 7,8-DHF; Angiogenesis; Exercise mimetics; Osteogenesis; ZIF-8.