Using network pharmacology to fabricate crosslinked hyaluronan–chondroitin sulphate-resveratrol composite hydrogels for cartilage regeneration

Abstract Cartilage tissue engineering provides a new approach for the treatment of cartilage damage. The combination of drug system with a tissue scaffold could be highly beneficial. Resveratrol (RES) is a potent anti-inflammatory agent, but its target genes and molecular mechanism of cartilage repair remain to be further studied. We used systems biology and network pharmacology methods to explore the mechanism of RES for chondrocyte and macrophages. Meanwhile, crosslinked hyaluronan–chondroitin sulphate-RES hydrogels (cHA-CS-RES) were constructed based on the target prediction results. By in vitro and in vivo experiments, we investigated its anti-inflammatory and pro-chondrogenesis. The results showed there were 12 hub genes potentially interacting in the RES-chondrocyte-macrophage network. In vitro experiments were used to further verify the validity of the predicted hub genes. The composite hydrogels were successfully fabricated, and maintenance of the characteristic was further confirmed. In vitro study, cHA-CS-RES showed high cell viability, anti-inflammatory and pro-chondrogenesis abilities. In vivo study of cartilage defects confirmed that the cHA-CS-RES groups were significantly better than the control group. Network pharmacology was used to predict and screen the target proteins of RES critical to cartilage tissue engineering. Moreover, cHA-CS-RES composite hydrogel showed good cartilage repair effects, anti-inflammatory and pro-chondrogenesis abilities.