Calcitriol-Loaded Multifunctional Nanospheres with Superlubricity for Advanced Osteoarthritis Treatment

Osteoarthritis (OA) is characterized by the lubricationdysfunctionof a cartilage sliding interface caused by chronic joint inflammation,and effective nonsurgical therapy for advanced OA remains lacking.Addressing chronic joint inflammation, lubrication dysfunction, andcartilage-tissue degradation simultaneously may hopefully tackle thischallenge. Herein, we developed superlubricative zein@alginate/strontium@calcitriol(ZASC) nanospheres to treat advanced OA. ZASC was confirmed to significantlyimprove joint lubrication through traditional tribological tests andour proposed tribological experiment to mimic the intra-articularcondition based on the human medial tibiofemoral joint tissues. Thisfinding was attributed to the hydration lubrication formed aroundthe alginate-strontium spheres that enabled ball-bearing lubricationand the filling of cartilage defects. Moreover, ZASCs that releasedcalcitriol in a sustained manner showed proliferative, anti-inflammatory,and anti-apoptosis effects in vitro. Further experimentsdemonstrated that ZASC exerted chondroprotective effects by inhibitingthe breakdown of the extracellular matrix in patient-derived OA cartilageexplants. In vivo results demonstrated that ZASCcan effectively maintain a normal gait to improve joint function,inhibit abnormal bone remodeling and cartilage degradation in earlyOA and can effectively reverse the advanced OA progression. Therefore,ZASC is a potentially nonsurgical therapeutic strategy for advancedOA treatments.