Sustained Release of Migrasomes from a Methacrylate-oxidized Hyaluronic Acid/methacrylated Gelatin Composite Hydrogel Accelerates Skin Wound Healing

Migrasomes are newly discovered organelles with diverse physiological and pathological functions. Recent studies have shown that the local injection of fibroblast-derived migrasomes can accelerate skin wound healing; however, their effects are short-lived. To extend their therapeutic effects, we developed a skin-mimicking hydrogel (OHG) composed of methacrylate-oxidized hyaluronic acid (O-HA-MA) and methacrylated gelatin (GelMA). Migrasomes purified from human fibroblasts were uniformly distributed within the composite hydrogel, as confirmed by scanning electron cryomicroscopy. In a rat skin wound model, this novel hydrogel (OHG@Mig) significantly enhanced re-epithelialization, promoted angiogenesis, collagen deposition, and cell proliferation, ultimately accelerating wound healing more effectively than free migrasomes. To investigate the underlying mechanisms, we analyzed RNA-seq data from previous studies and performed immunohistochemistry. Our findings suggest that the sustained release of migrasomes modulates tissue levels of CXCL12 and IL-6, contributing to enhanced wound healing. In conclusion, our study demonstrates that the sustained release of fibroblast-derived migrasomes from a composite hydrogel enhances their therapeutic effects on skin wound healing, offering a promising regenerative strategy.