Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by chronic inflammation and progressive cartilage degradation. Mesenchymal stem cell (MSC)-based therapies have demonstrated therapeutic potential; however, increasing evidence suggests that their efficacy primarily arises from paracrine factors, highlighting the potential of cell free approaches. In this study, we developed an injectable, thermosensitive composite hydrogel incorporating adipose-derived MSC (AD-MSC) supernatant within a Pluronic F-127 (PF-127)/sodium hyaluronate (HA) matrix. The hydrogel exhibited a solution state at a low temperature and rapidly transitioned into a stable gel at a physiological temperature without chemical crosslinkers. Microstructural analysis revealed a porous, interconnected three-dimensional network favorable for the sustained release of bioactive factors. In a rat model of KOA, intra-articular administration of the AD-MSC supernatant-loaded hydrogel significantly improved joint architecture and locomotor performance, alleviated synovial inflammation, and preserved cartilage integrity. Radiographic and histological assessments demonstrated reduced cartilage degeneration and subchondral bone alterations. Moreover, the treatment markedly decreased intra-articular levels of proinflammatory cytokines (IL-1β and TNF-α) and the cartilage degradation marker CTX-II in a time-dependent manner. These findings indicated that the sustained local delivery of AD-MSC-derived supernatant effectively modulated joint inflammation and attenuated cartilage degeneration, with the hydrogel serving primarily as a delivery vehicle for these bioactive factors. This cell-free injectable biomaterial platform could offer a promising therapeutic strategy for the treatment of knee osteoarthritis.

Aflatoxin B1 (AFB1), a common contaminant in broiler feed, impairs hepatic function and poses a significant threat to the poultry industry by disrupting cellular autophagy. Ferulic acid (FA) is a naturally occurring phenolic compound with antioxidant, anti-inflammatory, and autophagy-modulating properties. However, whether FA alleviates AFB1-induced autophagy impairment in broiler liver remains unclear. In this study, an AFB1-induced liver injury model was established. A series of experiments were conducted to evaluate the effects of AFB1 and FA on autophagy-related processes. The results showed that AFB1 exposure was associated with reduced expression of autophagy-related markers, including ULK1, ATG14, ATG5, and LC3-II/LC3-I ratio, suggesting alterations in autophagy-related processes associated with autophagosome formation and maturation. FA supplementation partially reversed these changes and alleviated ultrastructural liver damage induced by AFB1. Transcriptomic and western blot analyses further demonstrated that AFB1 exposure increased p53 expression, dysregulated the BRAF/ERK1/ERK2/mTOR signaling pathway, increased p70S6K expression, and decreased 4E-BP1 expression. FA supplementation alleviated these changes. These results showed that FA may alleviate AFB1-induced alterations in autophagy-related biomarkers in broiler liver, accompanied by changes in the BRAF/ERK1/ERK2/mTOR signaling pathway, suppression of p70S6K expression, and restoration of 4E-BP1 expression, which may contribute to its protective effects against AFB1-induced liver toxicity in broilers.