Mesenchymal stromal exosome-functionalized scaffolds induce innate and adaptive immunomodulatory responses toward tissue repair

Designing scaffolds capable of inducing and guiding appropriate immune responses holds promise for tissue repair/regeneration. Biofunctional scaffolds were here prepared by immobilizing mesenchymal stromal exosomes onto fibrous polyester materials and allowed cell-mediated delivery of membrane-bound vesicles. Quantitative cell-level analyses revealed that immune cells dominated the uptake of exosomes from scaffolds in vivo, with materials and exosomes acting as the recruiter and trainer for immune cells, respectively, to synergistically promote beneficial macrophage and regulatory T cell responses in skin wounds in mice. Adaptive T helper cell responses were found active in remote immune organs, and exosome-laden scaffolds facilitated tissue repair in large skin injury models. This study demonstrated important mechanisms involved in local and systemic immune responses to biological implants, and understanding tissue-reparative immunomodulation may guide the design of new biofunctional scaffolds.