miR-21 promotes osseointegration and mineralization through enhancing both osteogenic and osteoclastic expression

The demand for orthopedic implants continues to increase with the aging population. As the most widely used orthopedic materials, titanium and its alloys have achieved high success rates. However, the lack of bone tissue integration remains a barrier to successful operations. In this study, the titanium surface was acid-treated and functionalized with miR-21 nanocapsules via an in situ polymerization method. This coating showed a uniform miR-21 distribution and sustainable miR-21 release. The in vitro studies indicated that miR-21 could not only promote angiogenic and osteogenic differentiation of MSCs but also enhance osteoclastic activity. Additionally, in vivo evaluations, including X-ray, micro-CT, histology, immunohistochemistry, biomechanical testing, Raman and SEM-EDS, demonstrated that the micro-rough surface could increase the bone-implant contact and, thus, improved osseointegration during the early stages. More importantly, the miR-21 nanocapsule coating accelerated vascularization (high expression of CD31), bone remodeling (high expression of both osteogenesis- and osteoclast-related proteins) and bone maturation (high proportion of apatite), resulting in a significantly improved bone-implant contact and enhanced bone-implant bonding strength (twice the Ti at 1 month). These results indicated that a Ti-based micro-rough surface functionalized with miR-21 nanocapsules had potential applications in the orthopedic field.