Modulation of bone formation and resorption using a novel zoledronic acid loaded gelatin nanoparticles integrated porous titanium scaffold: An in vitro and in vivo study

Abstract

Osteoporotic bone defects are a major challenge in clinics for bone regeneration. With the condition of osteoporosis, excessive bone absorption and impaired osteogenesis result in unexpectedly long healing procedures for defects. In order to simultaneously enhance bone formation and reduce bone resorption, a polydopamine-coated porous titanium scaffold was designed, to be integrated with anti-catabolic drug zoledronic acid nanoparticles (ZOL loaded gelatin NPs), which was able to achieve a local sustained release of ZOL as expected. The in vitro study demonstrated that extracts of the composite scaffolds would stimulate osteoblast differentiation; they also inhibited osteoclastogenesis at a ZOL loading concentration of 50 μmol l-1. In the subsequent in vivo study, the composite scaffolds were implanted into ovariectomy-induced osteoporotic rabbits suffering from femoral condyles defects. The results indicated that the composite scaffolds without ZOL loaded gelatin NPs only induced callus formation, mainly at the interface margin between the implant and bone, whereas the composite scaffolds with ZOL loaded gelatin NPs were capable of further enhancing osteogenesis and bone growth into the scaffolds. Moreover, the research proved that the promoting effect was optimal at a ZOL loading concentration of 50 μmol l-1. In summary, the present research indicated that a new type of porous titanium scaffold integrated with ZOL loaded gelatin NPs inherited a superior biocompatibility and bone regeneration capability. It would be an optimal alternative for the reconstruction of osteoporosis-related defects compared to a traditional porous titanium implant; in other words, the new type of scaffold offers a new effective and practical procedure option for patients suffering from osteoporotic bone defects.