A Cellularized Marine Collagen-based Wound Dressing For The Treatment Of Skin Wounds: Observations In A Rodent Animal Model

*Purpose/Objectives: Skin wound healing is a dynamic process thatcomprises different overlapping phases that aims to restore the skinintegrity. However, a minimal impairment (e.g., infection) may lead tohard-to-heal ulcers or open non-closing wounds in a constant state ofinflammation. For this reason, an ideal treatment able to contain inflammation while promoting healing is necessary in the clinic. Wound dressings are materials used to cover and protect the wound from damagealong with maintaining its moisture, hence they are one of the gold standard treatments for wound care management in Veterinary Medicine.Besides dressings, cell therapy has also shown promising results, in particular the application of mesenchymal stem cells (MSCs). This cell population can release a plethora of soluble molecules that modulatedifferent biological processes such as inflammation. In this work wedescribe the application of a marine collagen-based wound dressing(MCDT) alone or in combination with allogeneic adipose-derivedMSCs (aMSCs) for the treatment of skin wounds in a rodent model.*Methodology: A total of 48 rats were included in the study. Onthe back of each animal two round wounds were surgically induced:to one aMSCs or the biomaterial, with or without cells (MCDT orMCDT+aMSCs), was applied (n = 16 per treatment) while one wasleft untreated. Wounds were checked daily for signs of adverse reactions or infection. After 5 and 10 days, skin samples were collectedand processed for histopathological (inflammation and granulationtissue (GT) presence) and gene expression analysis for factorsinvolved in the skin wound healing process (extracellular matrixproteins, growth factors, and pro-inflammatory cytokines).*Results: Clinically, at day 5 wound closure rate was similar amongtreatments. At day 10, MCDT-treated wounds showed a slightly lowerwound closure rate compared to treatment containing cells. At the histological level, the presence of inflammatory cells was comparable amonguntreated and MCDT-treated wounds while cell-based treatmentshowed a lower level of inflammation in the healing tissue. This observation is also reflected in the mRNA level of TNF-a and, especially, IL-1b,both well-known pro-inflammatory factors, which was lower in woundstreated with aMSCs and MCDT+aMSCs. All treated wounds alsoshowed a higher amount of GT on day 5 compared to untreated lesions.Moreover, while treated wounds showed a more mature GT at day 10,untreated lesions still displayed a high amount of immature GT. Theseresults are supported by the high expression of collagen type I and III inuntreated wounds, while treatments controlled collagen expression tobase levels at day 10. Moreover, higher levels of angiogenesis wereobserved in treated wounds, especially with MCDT+aMSCs, whichwere also characterized by a higher presence of vessels, especially in thelower layers of the tissue, and higher levels of PDFGb and VEGF.*Conclusion/Significance: In conclusion, all treatments led tobetter outcomes compared to physiological healing. Indeed, lowerinflammation and better deposition of structural proteins are crucialfactors to reach a proper level of skin wound healing after woundingand both elements were observed in this work