Microenvironment-Responsive Injectable Microspheres for Osteoarthritis Treatment via Oxidative Stress Inhibition and Sustained Lubrication.

Abstract

Oxidative stress imbalance and inadequate lubrication are the primary symptoms of osteoarthritis (OA), and they are also significant factors contributing to the progression of OA. Herein, an injectable hydrogel microsphere designed is presented to mitigate the progression of OA, comprising gelatin methacryloyl (GelMA), methacrylated hyaluronic acid (HAMA), 3-acrylamide-phenylboronic acid (3-AAPBA), chitin nanocrystals (ChNCs), and naringin (Nar). Specifically, positively charged ChNCs facilitated adhesion of microspheres to cartilage and enhanced their lubrication function. Furthermore, the phenyl borate bond incorporated within the microspheres enable the intelligent release of Nar in response to ROS and pH variations, thereby alleviating chondrocyte oxidative stress and restoring mitochondrial function. Most notably, the microspheres are capable of inhibiting chondrocyte senescence triggered by oxidative stress, preserving metabolic homeostasis in the cartilage extracellular matrix (ECM), and reducing inflammation levels. Overall, these hydrogel microspheres protect cartilage tissue and retard the progression of OA in vivo, providing a promising strategy for designing multifunctional materials targeting OA treatment.