Hierarchical zeolite coatings featuring a spatial gradient architecture for sequentially-controlled bisphosphonate release in the modulation of osteogenic–osteoclastic balance

Osteogenic–osteoclastic microenvironment imbalance impairs osseointegration between joint prostheses and the marrow cavity, which is a crucial contributor to the high incidence of complications such as implant loosening and periprosthetic fractures in osteoporosis (OPs). Previously, we employed hydrogel-based bisphosphonate (BPs) coatings on 3D-printed porous titanium alloy implants (pTi) to modulate the OPs microenvironment through controlled release. However, challenges persisted, including the limited duration of BPs release and associated organic material degradation-induced toxicity. To address these issues, we modified pTi surfaces by introducing chemically stable zeolites and BPs. In this study, we applied Ca2+-functionalized hierarchical zeolite coating on pTi for the first time. By combining mesoporous adsorption and Ca2+ chelation, we achieved efficient encapsulation of zoledronate (ZOL), creating a bioactive interface characterized by a spatial gradient structure with a "microporous-mesoporous-macroporous" morphology. The coating achieves the release of ZOL through the mesoporous structure and facilitates the gradual release of chelated ZOL via ion exchange, resulting in hierarchical drug delivery. Moreover, the spatial gradient structure of the coatings significantly influenced cell extension. Simultaneously, we constructed a bioactive coating with a drug concentration gradient, achieving graded drug release within the microenvironment, which facilitated the accurate regulation of osteogenesis and bone resorption. This coating has the potential to substantially enhance the management of postoperative complications in OPs patients undergoing prosthetic replacement surgery by achieving a balanced osteogenic-osteoclastic response.