76. An Adipose Stem Cell Derived Exosome Sheet Regulates Oral Mucosal Wound Healing

PURPOSE: Wounds in the oral cavity, whether caused by surgery or trauma, can lead to significant health and economic burdens. While the mechanisms of cutaneous wound healing are well-established, intraoral mucosal healing remains less explored, making treatment development more challenging. Adipose-derived stem cell (ADSC) exosomes present a promising therapeutic approach for mucosal wound healing. This study aims to investigate the effects of ADSC exosomes on oral mucosal wounds in a rat model. METHODS: A 1x1 cm2 full thickness excisional wound was created in the palate 16 Sprague-Dawley rats. 8 mice received occlusive covering (Control group) and 8 mice received an ADSC exosome sheet covered with occlusive dressing (ADSC-exo group). The ADSC-exo sheet was prepared by integrating lyophilized ADSC exosomes into a fibrinogen matrix. Wounds were monitored and photographed over 10 days for wound closure rate assessment. At day 10, tissue was harvested for histological and molecular analysis. Ex-vivo fibroblast migration assays were conducted to examine cellular responses to ADSC-exo. RESULTS: Use of ADSC-exo significantly accelerated wound closure (18±5% vs. 35±9% of initial area; p=0.002) and enhanced fibroblast migration (24 hr: 18% vs. 35% of initial area, p=0.001; 48 hr: 36% vs. 60% of initial area, p<0.0001) compared to the control group. Use of ADSC-exo increased re-epithelialization (87±14% vs. 21±6% wound coverage; p<0.0001), cellular proliferation (34±12 vs. 18±7 Ki67+/HPF; p=0.004), and neovascularization (28±9 vs. 11±5 CD31+/HPF; p=0.0002). Inflammation of the wound was significantly lower in the ADSC-exo group (4±1 vs. 13±9 CD68+/HPF; p<0.0001). Western blotting showed significant increase in TGFβ-1 (1.3±0.3 vs. 0.9±0.2; p=0.006) and Collagen I deposition (1.5±0.9 vs. 0.5±0.3; p=0.005), while downregulating Caspase-3 (0.7±0.3 vs. 1.1±0.2; p=0.003) and Bax (0.9±0.2 vs. 1.4±0.1; p<0.0001). CONCLUSION: Application of an ADSC-exo to rat mucosal wounds significantly improved wound healing, promoting cellular processes essential for tissue regeneration while reducing inflammation and apoptosis. Mechanistically these effects may be linked to upregulated TGF-β1 activity.