Recombinant human collagen hydrogels with different stem cell-derived exosomes encapsulation for wound treatment.

Exosomes-loaded hydrogels have potential value in wound treatment. Current studies focus on improving hydrogels' biocompatibility and optimizing different stem cell-derived exosomes for better therapeutic effect. Herein, we present a novel biocompatible recombinant human collagen (RHC) hydrogel loading with different MSCs-derived exosomes for promoting wound healing. We modify the RHC with methacrylate anhydride (MA) at optimal concentration, generating collagen hydrogel (RHCMA) with ideal physiochemical properties for exosome delivery (MSC-exos@RHCMA). Exosomes derived from human adipose-derived MSCs (ADSC-exos), bone marrow-derived MSCs (BMSC-exos) and umbilical cord MSCs (ucMSC-exos) are harvested from the culture supernatants and are loaded into RHCMA, respectively. These three hydrogel systems exhibit desired sustained release features, and can significantly improve cell proliferation and migration. In addition, these MSC-exos@RHCMAs show excellent therapeutic performance in treating the wounds of rats. Notably, we have demonstrated that the healing effect occurs best under the treatment of ucMSC-exos@RHCMA, following inflammatory resolution, angiogenesis, and collagen formation. These results would supply important value for the clinical application of MSC-exos in wound treatment in the future.