Ros-responsive nanocomposite scaffolds for sustained releasing puerarin to achieve chondroprotection in OA rats

[Display omitted] •ROS-responsive nanocomposite nanofibers were fabricated by using PCL, PEGDA-EDT and rGO, as stimuli-responsive drug delivery system.•The ROS-responsive nanocomposite nanofibers enabled high loading of puerarin, and facilitate efficient controlled release based on ROS condition in the OA microenvironment.•The PPE@rGO-Pue nanofibers exhibited favourable anti-inflammatory and antioxidative properties for chonro-protection.•The PPE@rGO-Pue nanofibers enable to downregulating the expression of IL-1β and MMP13, therefore limiting the cartilage degradation in OA model. Reactive Oxygen Species (ROS) plays an important role in osteoarthritis (OA) development and progression. Here, a ROS-responsive nanocomposite scaffold called PPE@rGO-Pue was fabricated by electrospinning, wherein PCL served as the backbone, PEGDA-EDT as the ROS responsive motif, and rGO as puerarin (Pue) carrier. The electrospun nanofibers composed of PEGDA-EDT and rGO exhibits accelerated Pue release behavior in the response to H2O2 through dose-dependent manner in 2 weeks. The interactions of PEGDA-EDT and Pue dramatically inhibits ROS production and activates antioxidant enzymes such as CAT, GSS, SOD, and GSH. Furthermore, the expression of inflammatory factor IL-1β had decrease significantly. Subsequently, PPE@rGO-Pue had shown chondro-protective effect for OA, which was evidenced by the suppression of MMPs, resulting in matrix degradation and the increase of Col2a1 and GAG that attenuated the cartilage erosion. In summary, this ROS-responsive electrospun nanofibers with sustained release of Pue exhibited antioxidative, anti-inflammatory, and chondro-protective potentials, suggesting that it could be an excellent drug carrier for OA therapy. This work may shed light on the design of antioxidative biomaterials for OA.