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.
Novel gold-shell nanoparticles (pH-GSNPs) are designed for the first time, which exhibit drug leakage-free behavior in a physiological environment, while achieving rapid drug release and remarkable aggregation for the nanogold interlayer of pH-GSNPs to shift their absorption to far-red and NIR as a photothermal agent in the intracellular microenvironment.
Mimicking and leveraging biological structures and materials provide important approaches to develop functional vehicles for drug delivery. Taking advantage of the affinity and adhesion between the activated endothelial cells and...
Cardiac patches are widely investigated to repair or regenerate diseased and aging cardiac tissues. While numerous studies looked into engineering the biochemical/biomechanical/cellular microenvironment and components in the heart tissue, the changes induced by cardiac patches and how they should be controlled to promote cardiac tissue repair/regeneration remains an important yet untapped direction, especially immunological responses. In this study, we designed and fabricated a bilaminated cardiac patch based on extracellular matrix (ECM) materials loaded with the extracellular vesicles (EVs) derived from mesenchymal stromal cells. The function of the biological material to modulate the injury-related microenvironment in a cardiac infarction model in mice was investigated. The study showed that the treatment of EV-ECM patches to the infarcted area increased the level of immunomodulatory major histocompatibility complex class II lo macrophages in the early stage of myocardial injury to mitigate excessive inflammatory responses due to injury. The intensity of the acquired proinflammatory immune response in systemic immune organs was reduced. Further analyses indicated that the EV-ECM patches exhibited proangiogenic functions and decreased the infarct size with improved cardiac recovery in mice. The study provided insights into shaping the injury-related microenvironment through the incorporation of extracellular vesicles into cardiac patches, and the EV-ECM material is a promising design paradigm to improve the function of cardiac patches to treat myocardial injuries and diseases.
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