Nanopatterned Titanium Implants Accelerate Bone Formation In Vivo

[Image: see text] Accelerated de novo formation of bone is a highly desirable aim of implants targeting musculoskeletal injuries. To date, this has primarily been addressed by biologic factors. However, there is an unmet need for robust, highly reproducible yet economic alternative strategies that strongly induce an osteogenic cell response. Here, we present a surface engineering method of translating bioactive nanopatterns from polymeric in vitro studies to clinically relevant material for orthopedics: three-dimensional, large area metal. We use a titanium-based sol–gel whereby metal implants can be engineered to induce osteoinduction both in vitro and in vivo. We show that controlled disordered nanotopographies presented as pillars with 15–25 nm height and 100 nm diameter on titanium dioxide effectively induce osteogenesis when seeded with STRO-1-enriched human skeletal stem cells in vivo subcutaneous implantation in mice. After 28 days, samples were retrieved, which showed a 20-fold increase in osteogenic gene induction of nanopatterned substrates, indicating that the sol–gel nanopatterning method offers a promising route for translation to future clinical orthopedic implants.