Bisphosphonate Delivery via a pH-Responsive Bone Implant for Accelerated Repair of Osteoporotic Bone Fractures

Osteoporotic fractures represent a major clinical and socioeconomic challenge due to prolonged healing times. Current osteoporosis therapies are primarily based on oral administration of bisphosphonates, which inhibit osteoclast-mediated bone resorption. However, additional local administration of bisphosphonates directly to the fracture site may prove to be an effective strategy, increasing drug concentration where it is most needed and thereby accelerating bone regeneration.

The aim of this study was to develop a multifunctional bone implant that provides mechanical support at the site of osteoporotic fracture while simultaneously enhancing bone regeneration through local, pH-responsive delivery of a bisphosphonate drug. The novel implant was composed of chitosan, agarose, nanohydroxyapatite, and a pH-responsive zeolite-chitosan-bisphosphonate complex, forming a drug-delivery platform. In this system, chitosan served as a linker binding risedronate sodium to the zeolite carrier. The bond between the zeolite and the drug was pH-responsive, and exposure to an acidic environment led to degradation of the chitosan linker and subsequent drug release. It was hypothesized that, following implantation, the biomaterial would encounter acidic microenvironments generated during osteoclast-mediated bone resorption, triggering localized bisphosphonate release and suppression of osteoclast activity. In this study, a comprehensive microstructural and biological evaluation of the developed implant was performed to assess its biomedical potential.

The results demonstrated favorable microstructural and mechanical properties comparable to cancellous bone, including a highly porous microstructure and increased surface roughness. Furthermore, the implant exhibited excellent cytocompatibility, hemocompatibility, and osteoconductivity. It was also shown that a bone implant supported osseointegration with human bone in an ex vivo model.

The proposed bone implant represents a promising platform for local bisphosphonate delivery in osteoporotic fracture treatment, although further advanced biological studies are required to fully confirm its clinical efficacy.

Acknowledgements: This research was funded by the National Science Centre in Poland within OPUS 22 grant no. UMO-2021/43/B/NZ7/00447.