Bone marrow-derived mesenchymal stem cells and extracellular vesicles enriched collagen chitosan scaffold in skin wound healing (a rat model)

Abstract

Background: Over the past ten years, regenerative medicine has focused on the regeneration and the reconstruction of damaged, diseased, or lost tissues and organs. Skin, being the largest organ in the human body, had attained a good attraction in this field. Delayed wound healing is one of the most challenging clinical medicine complications. This study aimed to evaluate the collagen chitosan scaffold's effect alone, or enriched with either bone marrow-derived mesenchymal stem cells (BM-MSCs) or their secreted extracellular vesicles (EVs) on the duration and quality of skin wound healing.

Methods: A full-thickness skin wound was induced on the back of 32 adult male Sprague-Dawley rats. The wounds were either covered with collagen chitosan scaffolds alone, scaffolds enriched with stem cells, or extracellular vesicles. Unprotected wounds were used as control. Healing duration, collagen deposition and alignment, CD 68+ macrophage count, and functional tensile strength of healed skin were assessed (α = 0.05, n = 8).

Results: The rate of skin healing was significantly accelerated in all treated groups compared to the control. Immuno-histochemical assessment of CD68+ macrophages showed enhanced macrophages count, in addition to higher collagen deposition and better collagen alignment in EVs and BM-MSCs treated groups compared to the control group. Higher tensile strength values reflected the better collagen deposition and alignment for these groups. EVs showed higher amounts of collagen deposition and better alignment compared to MSCs treated group.

Conclusion: The collagen chitosan scaffolds enriched with MSCs or their EVs improved wound healing and improved the quantity and remodeling of collagen with a better assignment to EVs.

Keywords: Collagen chitosan scaffold; extracellular vesicles; mesenchymal stem cells; tissue engineering; wound healing.