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

Compared to water-soluble osteogenic drugs, fat-soluble osteogenic drugs exhibit higher bioavailability and drug stability, making them valuable in enhancing 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. In this study, we 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. It was found that the hydrophilicity and loading capacity of fat-soluble osteogenic drugs strongly depend on the duration of acylation treatment. Our results demonstrate that the drug release mechanism involves 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 VD3 as a model drug confirm that the coating effectively promotes bone formation through high-efficiency delivery of VD3. Furthermore, in vivo experiments demonstrate that the VD3-loaded lipophilic surface significantly enhances osteogenic capability and improves osseointegration of titanium implants. This study provides a promising strategy for loading fat-soluble drugs on Ti implant and provides direct experimental evidence to demonstrate the significant value of fat-soluble drugs in promoting implant osseointegration.