Quercetin-based composite hydrogel promotes muscle tissue regeneration through macrophage polarization and oxidative stress attenuation

Skeletal muscle tissue cannot repair itself after volumetric muscle loss (VML) injury, which results in chronic inflammation and secondary injuries. Quercetin (QCN) possesses natural antioxidant properties and the ability of suppressing inflammation. Herein, an in situ photocurable composite hydrogel was developed by employing silk fibroin methacryloyl (SilMA) and decellularized extracellular matrix (ECM) derived from skeletal muscle. QCN loaded liposomes were introduced to create a local microenvironment which was conducive to skeletal muscle regeneration by regulating M2 polarization of macrophages and reducing oxidative stress. The SilMA-ECM-QCN composite hydrogel was characterized with suitable porosity, mechanical properties and degradation properties, as well as adhesion property for injury wound sealing via in situ polymerization. Moreover, the therapeutic effects of SilMA-ECM-QCN for promoting muscle regeneration and decreasing fibrosis were demonstrated by using a VML rat model. The results showed that the photocurable SilMA-ECM-QCN hydrogel had a huge advantage in the rapid filling of complex skeletal muscle tissue defects. Altogether, the present work could provide a promising strategy to create a pro-regenerative microenvironment for muscle regeneration by utilizing natural biomaterials.