Degradation-Dependent Self-Release Hydrogel with over Three Months of Antioxidation and Anti-inflammation for Osteoporotic Bone Repair

Abstract

Although hydrogel-loaded drugs hold potential for treating osteoporotic bone defects, there is no example that meets the release requirement for repair of >3 months owing to the difficulty in overcoming the diffusion drug release. Herein, a degradation-dependent self-release (DDSR) hydrogel that negated diffusion was developed by polymerizing only the natural antioxidant lipoic acid (LA). By controlling just the degradation rate of the hydrogel, the LA sustained release from the poly­(LA) backbone and achieved ∼4 months of antioxidation and anti-inflammation. After 12 weeks of implantation, the new bone formation ratio in osteoporotic bone defects treated using the DDSR hydrogel ran to 46 ± 5.7%, considerably higher than that of untreated defects (25.4 ± 4.2%) and even approaching that of normal bone repair (48.7 ± 7.1%). Notably, the DDSR hydrogel could also serve as carriers to load osteoinductive nanohydroxyapatite, thus further accelerating osteoporotic bone repair. The DDSR hydrogel with no diffusion constitutes the first hydrogel of >3-month drug release for osteoporotic bone repair.