A sericin scaffold loaded with supernatant from mesenchymal stem cells exposed to pro-inflammatory cytokines enhances wound healing

Our previous research established that treatment with IFN-γ and TNF-α (IT) significantly enhanced the paracrine activity of MSCs, resulting in a more effective wound healing response when applied to the wound surface with supernatant from IT-stimulated MSCs (S-IT MSCs). While S-IT MSCs hold promise for advancing wound healing therapy, challenges remain in developing an approach that enhances therapeutic efficacy and simplifies administration. This study proposed a scaffold composed of sericin, known for its skin regeneration properties, to load S-IT MSCs, designated as Se + S-IT MSCs, for the protection of bioactive factors. Additionally, whether Se + S-IT MSCs exhibit a superior effect on wound healing was investigated using a rat total skin excision model. Results indicated that Se + S-IT MSCs outperformed silk sericin loaded with MSC supernatant (Se + S-MSCs) in promoting migration, proliferation, and activation of HUVECs, HaCaTs, macrophages, and HDFs. Furthermore, Se + S-IT MSCs significantly promoted macrophage polarization toward the M2 phenotype, potentiated vascularization and re-epithelialization, and enhanced collagen deposition. These effects collectively accelerated wound healing in vivo in rats. This study highlights the potential of Se + S-IT MSCs to facilitate rapid and effective wound healing, with silk sericin scaffolds serving as efficient carriers to expedite the process.