The application of Mesenchymal Stem Cell-derived Exosomes Implanted on ovine small intestine submucosa in healing of Full-Thickness Cutaneous Wound in male rats

<title>Abstract</title> <p>IntroductionTreatment of full-thickness injuries poses challenges since these injuries tend to be hard to treat and come with high chances of infection, scarring, and other health risks. Traditional treatment methods such as skin grafting have several limitations, while current substitutes are unable to replace normal skin completely. Treatment using stem cell-derived exosomes has been proven efficient, although there are concerns regarding retention of exosomes in the area of injury. The use of exosomes combined with a scaffold material such as SIS can improve treatment efficiency by providing physical support and sustained therapy.Materials and MethodsDecellularized SIS scaffolds were obtained from a bovine source and characterized through DAPI staining and DNA measurement. MSC exosomes from human umbilical cords were isolated via ultracentrifugation and characterized through dynamic light scattering, transmission electron microscopy, flow cytometry, and Western blotting. Full-thickness wounds were inflicted on rats and treated with either SIS or SIS-Exo scaffold, and left untreated wounds served as controls. The wound healing was analyzed on day 14 by performing H&amp;E and Masson's trichrome staining along with semi-quantitative histological scoring and ImageJ analysis.ResultsSIS-Exo treatment showed significant improvement in wound healing in comparison to SIS and untreated controls. Histological evaluation revealed better granulation tissue formation, re-epithelialization, angiogenesis, and deposition of collagen in SIS-Exo treatment. Masson's trichrome staining revealed a significant increase in collagen deposition in SIS and SIS-Exo treatment as compared to the control, but higher collagen deposition was seen in the SIS-Exo group (P &lt; 0.001).ConclusionsThe combination of SIS with exosomes (SIS-Exo) has proven to be highly effective in wound healing in rats, improving tissue regeneration, collagen formation, and vasculature formation. There is a great deal of promise in its application in regenerative medicine; however, more studies are required to prove its efficacy.</p>