Bioactive and degradable collagen-based three-dimensional scaffold encapsulated with adipose mesenchymal stem cells-derived exosomes improved diabetic wound healing.

A diabetic wound is the most frequent form of chronic wound. Because diabetic wounds have multiple factors contributing to their development, the best treatments involve using a combination of approaches. Herein we assessed whether bioactive and degradable bioengineered micro-porous collagen-based three-dimensional scaffold (CTS) encapsulated with adipose mesenchymal stem cells (ASCs)-derived exosomes could accelerate the wound healing process in diabetic rats. Diabetic animals were assigned to the control group, CTS group, Exo group, and CTS+Exo group. Tissue samples were collected on days 7, 14, and 21 for evaluations including stereological, molecular, and tensiometrical assessments. The findings showed that in the treatment groups, there was a notably increase in wound closure rate, total volumes of newly formed epidermis and dermis, numerical densities of fibroblasts and blood vessels, collagen density, and biomechanical parameters than the control group, with the most noticeable changes seen in the CTS+Exo group. Additionally, there was a notably increase in the transcript of miRNA-146a, TGF-β, bFGF, and VEGF genes in the treatment groups than the control group, with the highest expression observed in the CTS+Exo group. In the CTS+Exo group, there was a much greater decrease in TNF-α and IL-1β expression, as well as in the number of neutrophils, compared to the other groups. These results validated that the combination of CTS and ASCs-derived exosomes has a greater effect on improving diabetic wound healing.