An injectable ROS-responsive PRP-loaded hydrogel attenuates osteoarthritis by reducing oxidative stress, inflammation and chondrocyte apoptosis.

Abstract

Osteoarthritis (OA) is a degenerative joint disease mainly characterized by oxidative stress, inflammatory responses, and loss of cartilage matrix. Although platelet-rich plasma (PRP) has been applied in OA treatment, its intra-articular use is still limited by insufficient local retention and short duration of action. To address this issue, we constructed a reactive oxygen species (ROS)-responsive injectable hydrogel based on quaternized chitosan and tannic acid and loaded it with PRP (PRP@QCTH) as a local delivery strategy for OA treatment. The hydrogel showed favorable injectability, gel-forming ability, and ROS-responsive release behavior. In vitro experiments demonstrated that, compared with the model group, PRP@QCTH improved chondrocyte viability, reduced apoptosis and intracellular ROS accumulation, decreased the levels of IL-1β, TNF-α, and IL-6, and partially restored the expression of Aggrecan and COL2A1. In vivo evaluation further demonstrated that PRP@QCTH alleviated cartilage degeneration, preserved cartilage matrix integrity and improved subchondral bone-related parameters in OA joints, as confirmed by histological and cartilage-specific marker analyses. Transcriptomic analysis suggested that these protective effects might be associated with pathways involved in inflammatory regulation, extracellular matrix remodeling and tissue repair. In conclusion, PRP@QCTH showed protective effects in experimental OA and may serve as a potential local intervention strategy.