Implantable and degradable antioxidant poly(ε-caprolactone)-lignin nanofiber membrane for effective osteoarthritis treatment

Abstract

Osteoarthritis (OA) is one of the most common musculoskeletal disorders worldwide. Oxidative stress initiated by excessive free radicals such as reactive oxygen species (ROS) is a leading cause of cartilage degradation and OA. However, conventional injection or oral intake of antioxidants usually cannot provide effective treatment due to rapid clearance and degradation or low bioavailability. Here, a new strategy is proposed based on nanofibers made of poly (ε-caprolactone) (PCL) and PCL-grafted lignin (PCL-g-lignin) copolymer. Lignin offers intrinsic antioxidant activity while PCL tailors the mechanical properties. Electrospun PCL-lignin nanofibers show excellent antioxidant activity, low cytotoxicity and excellent anti-inflammatory effects as demonstrated using both H2O2-stimulated human chondrocytes and an OA rabbit model. PCL-lignin nanofibers inhibit ROS generation and activate antioxidant enzymes through autophagic mechanism. Arthroscopic implantation of nanofibrous membrane of PCL-lignin is effective to OA therapy because it is biocompatible, biodegradable and able to provide sustained antioxidant activity.