An Enhanced Osseointegration of Titanium Implants by H2S Sustained‐Release Coating via Promoting Osteogenesis and Inhibiting Osteoclastogenesis

Abstract The surfaces of titanium implants lack the ability of promoting osteogenesis and inhibiting osteoclastogenesis, which primarily contributes to their inadequate integration with surrounding bone tissue in osteoporotic environments. Developing a bioactive coating for the materials is regarded as a promising approach to address the challenge. In this study, a hydrogen sulfide (H 2 S) sustained‐release coating is fabricated on the surfaces of titanium implants. The coating consists of bovine serum albumin nanoparticles encapsulating the H 2 S donor morpholin‐4‐ium(4‐methoxyphenyl)‐morpholin‐4‐ylsulfanylidenesulfido‐λ 5 ‐phosphane (GYY4137), which is prepared with the participation of dopamine self‐polymerization. The release rate of H 2 S could be precisely controlled by adjusting the crosslinking degree of the nanoparticles. The coating proves to have excellent biocompatibility and satisfactory hemocompatibility. In vitro, the coating could significantly promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and inhibit the osteoclastic differentiation of mouse monocytic macrophage leukemia cells (RAW264.7 cells). In vivo, this work successfully verifies the conclusion obtained in vitro experiments. The coating restores the bone homeostasis imbalance surrounding the functionalized titanium implants in the femurs of osteoporotic rats, thereby accelerating new bone formation and enhancing the osseointegration capability of the implants. This work provides a practical strategy for the development of titanium implants suitable for osteoporosis patients.