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

Abstract

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.

Stem Cell-Derived Nanovesicles: A Novel Cell-Free Therapy for Wound Healing

“…The development of the active composition of CDN-laden scaffolds that appropriately interact with the immune system is facing a huge challenge. Studies have found that immune cells can absorb exosomes from the scaffold with more priority, which means that the body's immune response is important in tissue response [ 58 ].…”

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

“…Exosomes, known as membrane-enclosed extracellular vesicles (EVs) that carry proteins and nucleic acids, might represent another type of delivery system of bioactive molecules [ 180 ]. Su et al developed biofunctional scaffolds by fixing mesenchymal stromal exosomes (Exo) to electrospun randomly oriented fibrous polyester materials (PEF) [ 156 ]. The fabricated scaffolds were examined in skin injury models of sham mice to understand the immunomodulatory effects of mesenchymal stromal exosomes (Exo) in vivo [ 156 ].…”

The Therapeutic Potential of Mesenchymal Stromal Cells for Regenerative Medicine: Current Knowledge and Future Understandings

“…Recently, scaffolds and exosomes from mice BM-MSCs were developed as a combinatorial cell-free system to initiate synergistic tissue immunotrophic effects. Indeed, exosome-laden scaffolds (fibrous polyester materials) proactively facilitated tissue repair in mice skin injury models by favoring M2/T H 2/Treg responses ( Su et al, 2021 ). Together, all these findings indicate that combined HA and MSCs may constitute an effective strategy in regenerative medicine.…”