Augmenting osteoporotic osseointegration through a temporal release nanocoating-based reversing dysregulated...

Imbalances in the osteogenic-osteoclastic microenvironment hinder effective osseointegration between the prosthesis and host bone, which is a key factor contributing to the high incidence of prosthesis loosening and periprosthetic fractures in osteoporosis patients. Developing an implant interface that can reverse the dysregulated osteogenic microenvironment is an effective strategy to address this challenge.

A novel bioinspired interface with a spatial gradient structure was engineered by 3D-printed porous titanium alloy implants and hollow mesoporous silica nanoparticles coating. Apart from the bioinspired bone microstructure, the amine-functionalized nanocoating of the bioactive interface could also load and temporally sustain the zoledronic acid (ZOL) release. A series of in vitro experiments were carried out to characterize the bioactive interface and to clarify the regulation of osteogenic-osteoclastic balance by ZOL temporal release from the nanocoatings. Afterward, an osteoporotic model was utilized to validate the in vivo bioactive interface osseointegration effect.

Based on the structural features and chemical properties of the bioactive interface, efficient ZOL loading was achieved. Additionally, the temporal release mechanism of ZOL through free diffusion and ionic bond ionization enabled long-term sustained release. Meanwhile, the early high-concentration local release of ZOL effectively inhibited osteoclast formation and activation in the microenvironment. As the ZOL release decreased over time, the focus shifted to promoting the process of bone formation, thereby reversing the dysregulated osteogenic microenvironment. According to this, we identified the optimal gradient concentration (10^-5M) of the ZOL temporal release system that efficiently exerts bidirectional regulatory effects. Most notably, the spatial gradient structured interface loaded with this optimal concentration of ZOL (10^-5M) significantly augmented osseointegration under in vivo osteoporotic conditions.

Overall, our study provides a novel nanocoating capable of temporally releasing ZOL to reverse the dysregulated osteogenic microenvironment, aiming to maintain the long-term stability of artificial prostheses for osteoporosis patients.

This study validates the structure-performance-effect relationship of ZOL-releasing nanocoatings with a temporal release mechanism, providing a novel approach to addressing the high incidence of postoperative complications in osteoporotic patients undergoing prosthetic replacement.