Implantable Polyacrylonitrile-Spermidine Electrospun Nanofibers with Sustainable ROS Scavening Capacity for Osteoarthritis (OA) Therapy

Abstract Osteoarthritis (OA) is a major cause of mobility impairment in the elderly. Scavenging excessive reactive oxygen species (ROS) to inhibit oxidative stress damage is a theraupetic strategy for OA. However, low clearance efficiency, rapid clearance by the joint fliud, poor stability and lack of sustainability challenged most ROS scavengers. Herein, we innovatively synthesized a spermidine (SPD)-acrylonitrile (PAN) copolymer nanofiber membrane using electrostatic spinning technology for effective treatment of OA, wherin SPD that has potent antioxidant ability served as ROS scavenger and PAN as backbone for sustainable release of SPD. Compared with the PAN, the PAN-SPD nanofibers not only greatly improved the mechanical properties, but also exhibited the sustainability and high efficiency to scavenge ROS. Moreover, PAN-SPD nanofibers have good biocompatibility, and can effectively reduce oxidative stress damage in H2O2 induced chondrocytes by down-regulating the expression of pro-inflammatory factors like MMP-13, IL-6 and TNF-α while up-regulating the antioxidant factors such as (SOD, CAT, GSH). There was a dramatic reduction in OA severity after PAN-SPD nanofibrous membrane treatment in OA joints compared to the untreated group after a 8-week therapy. Overall, this study provides effective strategies and new ideas for the future clinical treatment of OA or oxidative stress-related diseases.