3D-MSCs A151 ODN-loaded exosomes are immunomodulatory and reveal a proteomic cargo that sustains wound resolution

•The MSC-derived secretome from 3D cultures enhances fibroblast and keratinocyte mitogenic and motogenic capacity in vitro, respectively.•The cargo of the 3D MSC-derived exosomes (Exo3D) reveals wound healing-related proteins and promotes wound resolution in a wound healing in vivo model.•Loading MSC-derived exosomes with A151 ODN further reduces the systemic levels of IL-6 and TNF-α pro-inflammatory cytokines at the late stage of wound healing in vivo, crucial for a full regenerated tissue.•A151-loaded Exo3D have a great potential as a noncellular off-the-shelf therapy for non-healing wound treatment.