Intra‐Articular Injectable Chitosan‐PVA Hydrogel Ingrained With Gallic Acid Loaded Mesoporous Silica Nanoparticles for Pain Relief and Cartilage Regeneration in Obese Osteoarthritic Rats

ABSTRACT Intra‐articular viscosupplementation with hyaluronic acid‐based injections in osteoarthritic joints provides temporary symptomatic relief but requires multiple doses, causing discomfort and higher costs. A smart dual‐functional hydrogel enhancing drug delivery and cartilage regeneration is a promising alternative. In this study, we fabricated an intra‐articular Chitosan‐PVA hydrogel ingrained with gallic acid‐loaded amino‐functionalized mesoporous silica nanoparticles (AF‐MSNs). Cytotoxicity analysis using MG‐63 cell lines confirmed its non‐toxic nature, supporting its use in experimental models. The hydrogel combination can be effectively injected into the knee joint in collagenase‐induced osteoarthritic high‐fat diet (HFD) female Wistar rats. qRT‐PCR analysis revealed a substantial decrease in the gene expression levels of MMP‐9 and MMP‐13, the catabolic enzymes involved in cartilage degeneration, in Ch‐PVA hydrogel + AF‐MSNs/GA treated IL‐1β induced rat chondrocyte cells. Behavioral studies provided evidence of pain alleviation in the experimental animals, as demonstrated by improvements in both the knee bend test and gait scoring. Histomorphological analysis of the articular cartilage revealed a significant improvement in the rebuilding of the cartilage matrix and a substantial increase ( p < 0.001) in the sulfated glycosaminoglycan (sGAG) contents. These findings underscore the therapeutic value of intra‐articular administration of Ch‐PVA hydrogel, enabling the sustained release of gallic acid from AF‐MSNs in a rat model of osteoarthritis. The treatment effectively promotes extracellular matrix (ECM) synthesis and facilitates cartilage matrix regeneration, supporting its potential as a disease‐modifying strategy for osteoarthritis.