1534 Early application of miRNA-21 overexpressing exosomes improves skin function and reduces scar formation

Hypertrophic scars result from sub-optimal wound healing and are characterized by excessive permanent differentiation of dermal fibroblasts into muscle-like myofibroblasts. While most treatments aim to reduce once they formed, early interventions accelerate closure will the over-activation myofibroblasts may prevent scar development. Exosomes showed promise in reducing fibrosis various disease models these effects were mediated miRNA-21 (miR-21). miR-21 targets inhibitory Smad7 enhance Smad2/3 translocation nucleus form a complex with epigenetic modulators that activate expression fibrotic mesenchymal regulatory factors essential for myofibroblast phenotype. Using Red Duroc Porcine (RDP) model scarring postburn, we tested ability adipose-derived stem cells overexpressing mi-R21 healing, improve skin function, potential Human miR21-exosomes, control naive exosomes embedded hydrogel formulation topically applied full-thickness burn wounds at 1,3,7, 14 days after excision grafting. Burn monitored closure, re-epithelization, neovascularization, epidermal water loss between 7 120 days. Skin biopsies collected over time analyzed thickness extracellular matrix protein expression. miR21-exosomes reduced day when compared controls. Exosome reduces rigidity 56 other (p< 0.05). collagen 1, smooth muscle actin, fibronectin, decorin (p<0.05) 60 90 These data suggest topical application injury function formation.