74. Comparative Analysis of Acellular Dermal Matrices as Vehicle for Stem Cell Therapy Delivery

PURPOSE: Chronic wounds present a significant clinical challenge, necessitating innovative approaches to enhance the wound healing process. Acellular dermal matrices (ADM) have emerged as promising biomaterials for wound management and may serve as effective scaffolds for stem cell therapy (1, 2). This study aims to compare the potential of four ADMs made from different origins (i.e. human, bovine, porcine, and fish), processing methodologies, and the presence of a basement membrane, as scaffolds for stem cell therapy to augment wound healing. METHODS: ADM A was the most processed, did not have a basement membrane, and derived from components of human, bovine, and porcine dermis; ADM B and D had moderate processing, did have a basement membrane, and was derived from human dermis; ADM C had little processing, no basement membrane, and was derived from fish dermis. All ADMs required rehydration, except ADM D. In vitro evaluations were performed using ToxiLight assays to assess cell viability, MTT assays to measure cell proliferation, and DAPI staining to visualize nuclear morphology, cell location, and migration. Murine epithelial stem cells (ESCs) were seeded onto each ADM. The cellular responses were compared with respective control groups, each ADM without stem cell seeding. RESULTS: ToxiLight assays revealed that all four ADMs supported cell viability. ADM A and C demonstrated the highest stem cell viability, followed by ADM D then C exhibiting slightly lower cell viability. MTT assays demonstrated increased cell proliferation on day nine after seeding for all ADMs, except ADM D. ADM B and C exemplified the most proliferation by day 9. DAPI staining confirmed the attachment and spreading of ESCs on all ADMs. CONCLUSIONS: Our in vitro study suggests that ADM C, then A exhibit superior performance as potential carriers for stem cell therapy, promoting higher cell viability and proliferation compared to ADM B and D. The results suggest there may be improved stem cell seeding in ADMs that are less processed. Interestingly, there was better ESC viability in ADMs that included components of xenograft and in ADMs that required rehydrating before stem cell seeding. The presence of a basement membrane did not seem to affect ESC viability. The findings underscore the importance of carefully selecting ADMs to optimize their role as stem cell therapy delivery platforms in wound healing applications. Further investigations are warranted to validate these findings in vivo models and ultimately translate them into clinical practice. REFERENCES 1. Dai C, Shih S, Khachemoune A. Skin substitutes for acute and chronic wound healing: an updated review. Journal of Dermatological Treatment. 2020 Aug 17;31(6):639-48. doi/full/10.1080/09546634.2018.1530443. 2. Meleshina AV, Bystrova AS, Rogovaya OS, Vorotelyak EA, Vasiliev AV, Zagaynova EV. Tissue-engineered skin constructs and application of stem cells for creation of skin equivalents. 2017;9(1 (eng)):198-218.