Hydrophobic Coating Platforms for High‐Efficiency Loading and Direct Transmembrane Delivery of Fat‐Soluble Osteogenic Drug for Enhanced Osseointegration of Titanium Implants

Abstract

Compared with water‐soluble osteogenic drugs, fat‐soluble osteogenic drugs exhibit higher bioavailability and drug stability, making them valuable for enhancing the osseointegration of implants. However, existing drug‐loading coatings are primarily designed for water‐soluble drugs, limiting their effectiveness in loading and delivering fat‐soluble osteogenic drugs. This study employed alkali treatment, silanization, and oleic acid acylation to sequentially modify the surface of Ti alloy, aiming to fabricate surfaces capable of efficiently loading and delivering fat‐soluble osteogenic drugs. Results show that the hydrophilicity and loading capacity of fat‐soluble osteogenic drugs strongly depended on the duration of the acylation treatment. Furthermore, the drug release mechanism involved direct diffusion from the coating to the cells in contact, resulting in improved bioavailability, as opposed to diffusion into the surrounding medium and subsequent cellular uptake. In vitro experiments using vitamine D3 (VD3) as a model drug confirmed that the coating effectively promoted bone formation through the highly efficient delivery of VD3. Furthermore, in vivo experiments demonstrated that the VD3‐loaded lipophilic surface significantly enhanced osteogenic capability and improved the osseointegration of titanium implants. This study provides a promising strategy for loading fat‐soluble drugs onto Ti implants and direct experimental evidence demonstrating the significant value of fat‐soluble drugs in promoting implant osseointegration.