Nano-enzymatic functionalized dual network hydrogel promotes tendon repair by modulating the inflammatory cycle and cellular behavior

Abstract

Tendon injuries are prone to adhesions after repair, which in turn lead to limb dysfunction, which remains a major challenge in clinical treatment. Current research suggests that tendon injuries are affected by the accumulation of reactive oxygen species (ROS), inflammatory responses, and type III collagen deposition. These factors lead to an imbalance between extrinsic and intrinsic tendon healing and are the main reasons for the occurrence of peritendinous adhesions. In this study, we constructed a carrier using a polyvinyl alcohol/polyethylene glycol (PVA/PEG) dual network hydrogel and loaded it with zeolite imidazolium ester framework-8@CeO₂ nano-enzymes (ZIF-8@CeO₂) to form a nano-enzyme-functionalized hydrogel (PVA/PEG/ZIF-8@CeO₂) therapeutic system. The surface of PVA/PEG/ZIF-8@CeO₂ is rich in hydrophilic hydroxyl groups that form hydrogen bonds with water molecules, creating a hydrated layer that inhibits fibrin adsorption and fibroblast adhesion, reduces the impact of exogenous healing, and reduces the formation of adhesions. Similarly, the loaded ZIF-8@CeO₂ has catalase (CAT) and superoxide dismutase (SOD) activities, which can effectively remove the excessive ROS in the injured tendon, down-regulate the inflammatory response, enhance the tendon differentiation of tendon stem cells, promote intrinsic healing, and ultimately promote the repair of injured tendons. Furthermore, the system can accelerate the transition from inflammation to repair and remodeling in the tendon healing process. The PVA/PEG/ZIF-8@CeO₂ treatment system is a novel approach for reducing peritendinous adhesions and effectively promoting the repair of injured tendons.