With the elevation of the social population all around the world, the prevalence of osteoarthritis (OA) is increasing year by year, what was more, the prevalence of people over 60 has exceeded 50 % in social people [[1], [2], [3]]. Not only the prevalence increases year by year, but also the age is getting younger [4]. Due to the high disability ratio of OA, it has become the most concerning disease among patients with skeletal and muscular motor system disorders [5]. However, drug treatments for OA, such as oral glucosamine, are not effective. Keller & Laurence Patients with grade 3 to 4 OA usually can only seek total knee replacement surgery to relieve OA symptoms and improve their quality of life. However, it is expensive, has high surgical risks, and has a long postoperative recovery period, making patients unable to bear the financial, psychological, and family burdens.

Resveratrol is a bioactive ingredient found in wine and grape juice, and a non-flavonoid polyphenol organic compound, which is an antitoxin produced by many plants. Hydrogel is a new type of drug carrier used to encapsulate drugs [6]. It has good lubricity and biocompatibility with tissues, especially for joints and other tissues that require lubrication. Studies have now reported that hyaluronic acid hydrogel has a good chondroprotective effect in OA, which may be achieved by lubricating the joint cavity and protecting the articular cartilage [[7], [8], [9]]. What’s more, new types of hydrogel need to be prepared for efficiency use. Therefore, using cyclodextrin to wrap Res to make hydrogels may play a consequential role of lubricating and supporting joints in the joints through the slow release of resveratrol. And its therapeutics of Res hydrogels must be verified.

As a non-specific Sirt1 agonist, Res effectively promotes the expression of Sirt1. Many studies have proved that Res effectively relieves OA in vitro and in vivo [[10], [11], [12]]. Several previous studies have shown that SIRT1 inhibits the HIF1α/MMP13 signal pathway in many diseases, such as reprogramming endothelial cells to suppress HIF1α [13], being a key mediator of tubulointerstitial damage in the aged kidney [14], and inhibiting the growth of bladder cancer in organoids [15]. While it has many protective effects on cell apoptosis, degradation and hypertrophy, the Res hydrogels’ efficient roles must be understood. Thus, the underlying mechanisms of Res on OA remained to be unlocked.

In this study, a temperature-sensitive Res hydrogel was prepared. After a weekly administration, it was found that it protects OA articular cartilage from degradation. At the same time, Res inhibits HIF1α by activating SIRT1 to promote the proliferation of chondrocytes and inhibits the hypertrophy of chondrocytes. Taken together, Res hydrogel protects the articular cartilage and reduces the damage to the joints caused by mechanical stress.