Abstract

ObjectiveDifficulty in wound healing is one common complication of diabetes mellitus. The study explored whether the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic ulcer wound was enhanced by the activation of the Wnt signaling pathway.MethodsRat diabetic model was established by intraperitoneal injection of Streptozotocin (STZ). hUCMSCs were purified and seeded on the collagen–chitosan laser drilling acellular dermal matrix (CCLDADM) scaffold, which was subsequently implanted into the cutaneous wound of normal and diabetic rats, followed by daily injection of Wnt signaling pathway agonist (Wnt3a) or antagonist (sFRP3) at the edge of the scaffold. Wound healing was checked on days 7, 14, and 21, and the fibrous tissue deposition, capillaries, and epidermal regeneration at the wound were examined by hematoxylin–eosin staining. The hUCMSCs-CCLDADM scaffold was cultured in vitro and treated with Wnt3a or sFRP3, followed by evaluation of cell proliferation, cell proliferation rate, survival status, and altered protein levels in the Wnt signaling pathway using BrdU staining, CCK-8 assay, live/dead staining, and Western blotting, respectively.ResultsOn days 7 and 14 postoperatively, the speed of wound healing was significantly lower in diabetic rats than that in normal control rats. This phenomenon was significantly improved by the activation of the Wnt signaling pathway that also elevated the fibrous protein deposition and the abundance of capillary in the granulation tissue. Conversely, blockade of Wnt signaling slowed the healing of skin wound in diabetic rats. The activation of Wnt signaling pathway promoted the proliferation and differentiation and decreased the apoptosis of hUCMSCs, thereby elevating the number of living hUCMSCs on the CCLDADM scaffold, while the suppression exerted a contrary effect.ConclusionThe activation of the Wnt signaling pathway promotes the healing of diabetic skin wound by the regulation of proliferation and differentiation of hUCMSCs on the CCLDADM scaffold.

Highlights

  • Diabetic ulcer is one of the major complications of diabetes that accounts for about 36% of all chronic skin ulcers, and the amputation rate is up to 19.03% in individuals with diabetic ulcers [1]

  • Activation of the Wnt signaling pathway improved the therapeutic effect of Human umbilical cord mesenchymal stem cells (hUCMSCs)‐loaded collagen–chitosan laser drilling acellular dermal matrix (CCLDADM) scaffold on diabetic wounds The skin wound healing area was measured on days 7, 14, and 21 postoperative and the rate of wound healing was found to be significantly lower in diabetic rats than that in normal rats on days 7 and 14

  • This phenomenon was significantly improved by the activation of the Wnt signaling pathway in diabetic rats, while it was slowed by the blockade of the pathway (Fig. 2a, b)

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Summary

Introduction

Diabetic ulcer is one of the major complications of diabetes that accounts for about 36% of all chronic skin ulcers, and the amputation rate is up to 19.03% in individuals with diabetic ulcers [1]. To improve the survival ratio of hUCMSCs on the wound surface, we implanted hUCMSCs on the scaffold made of the collagen–chitosan laser drilling acellular dermal matrix (CCLDADM), which was spread on the wound surface, to achieve the optimal therapeutic effect on the wound repair [6]. Whether this method could be feasible for the management of refractory diabetic ulcer wound necessitates further exploration

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