An injectable and photocurable methacrylate-silk fibroin/prussian blue nanozyme hydrogel with antioxidant and pyroptosis suppression properties for cartilage regeneration

Cartilage injury is one of the most prevalent, distressing, and disabling chronic conditions affecting degenerative joints worldwide; however, its underlying mechanisms remain elusive. Various biomaterials have been widely employed in the treatment of articular cartilage (AC) injuries. Despite these efforts, the key role of reactive oxygen species (ROS) as primary instigators of pyroptosis, combined with the lack of effective interventions, often results in suboptimal cartilage repair outcomes. Thus, there is an urgent need for the development of novel antioxidants and inflammasome-mediated pyroptosis modulators to create a favorable microenvironment for cartilage repair. In this study, we synthesized Prussian blue nanoparticles (PBNPs) capable of efficiently scavenging ROS. In vitro, these PBNPs protected against oxidative stress-induced cytotoxicity, preserved mitochondrial integrity, reduced the activation of nucleotide-binding domain and leucine-rich repeat family pyrin domain-containing 3 (NLRP3) inflammasomes and caspase-1, and subsequently downregulated gasdermin D (GSDMD) cleavage and inflammatory factor production, leading to the inhibition of chondrocyte pyroptosis. To extend these findings in vivo, we developed an injectable and photocurable methacrylate-silk fibroin (SilMA) hydrogel with homogeneously incorporated PBNPs, designed for releasing PBNPs. The resulting PBNPs@SilMA hydrogel decreased ROS production, reduced chondrocyte pyroptosis, and supported chondrocyte proliferation and matrix secretion, subsequently improved AC repair. Overall, our results indicate that the PBNPs@SilMA platform holds significant promise as a therapeutic strategy for AC injury.