The fibroblast-myofibroblast transition marked by extracellular matrix (ECM) secretion and contraction of actomyosin-based stress fibers, plays central roles in the wound healing process. This work aims to utilize a cell membrane-based nanoplatform to improve the outcomes of dysregulated wound healing. The cell membranes of myofibroblasts are isolated from mouse skin, and used as a camouflage to encapsulate gold nanoparticles with an adjuvant cytokine of IL-4. The membrane-camouflaged nanoparticles show effective in situ clearance of bacterial infection, and act as an activator in IL-4Rα signaling pathway to induce macrophages in pro-inflammatory M1 subtype into an anti-inflammatory M2-phenotype. Thus, the poor bacteria-clearance and non-stop inflammation in refractory wounds are improved and accelerated. Next, the nanoplatform releases myofibroblast membranes to further propel primitive fibroblasts to undergo a fibroblast-myofibroblast transition in an epigenetic manner. Matrix-production, vascularization, and epithelial regeneration are then initiated, leading to a satisfactory wound closure. Our study devises a new strategy to create an epigenetic modification for fibroblasts to turn into myofibroblasts under the prolonged and continuous exposure to a fibrotic environment, and develops a promising biomimetic nanoplatform for effective treatment of dysregulated chronic wound healing.
Keywords: cell membrane; epigenetic modification; fibroblast-myofibroblast transition; proliferation phase; wound healing.
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