A smart photothermal microneedle system for dual-targeted therapy of osteoarthritis via MMPs inhibition

Temporomandibular joint osteoarthritis (TMJ-OA) causes chronic pain, cartilage degeneration and pathological neurovascular remodeling, yet effective local therapies remain limited. Here we develop a minimally invasive near-infrared (NIR)-responsive microneedle system (SFZICC MNs) that integrates cryptochlorogenic acid (CCA)- and carbon quantum dot-loaded ZIF-8 nanoparticles within a methacrylated silk fibroin hydrogel. The system provides mechanical integrity, photothermal responsiveness and NIR-assisted local drug release. In a mouse TMJ-OA model, SFZICC MNs combined with NIR irradiation reduce mechanical hypersensitivity, anxiety-like behaviors, cartilage degeneration and pathological neurovascularization, and outperform free CCA, blank microneedles and drug-loaded microneedles without NIR. Mechanistically, CCA directly interacts with MMP3, MMP9 and MMP13 and moderately inhibits their catalytic activities in vitro, while reducing intracellular superoxide accumulation, NF-κB p65 phosphorylation and MMP protein abundance. In vivo imaging further supports reduced overall MMP-associated proteolytic activity. These findings support SFZICC MNs as a locally responsive therapeutic platform for TMJ-OA. Temporomandibular joint osteoarthritis (TMJ-OA) lacks effective local therapies. Here, the authors develop an NIR-responsive microneedle patch that locally delivers cryptochlorogenic acid (CCA), reduces pain and cartilage degeneration, and suppresses MMP-associated pathological remodeling.