Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells

Abstract

There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7 days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. Statement of Significance The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations.

Osteogenic potential of stem cells‐seeded bioactive nanocomposite scaffolds: A comparative study between human mesenchymal stem cells derived from bone, umbilical cord Wharton's jelly, and adipose tissue

“…The life quality of many people worldwide has been affected by bone diseases such as osteoporosis, Paget's disease, or cancer . Up to now, many studies have been conducted to provide innovative solutions for the reconstruction of damaged tissues . For successful reconstruction of bone tissues, three main factors were determined including appropriate cell sources, carriers for cell delivery such as scaffolds, and osteogenic growth factors .…”

“…[1][2][3] Up to now, many studies have been conducted to provide innovative solutions for the reconstruction of damaged tissues. 4,5 For successful reconstruction of bone Additional Supporting Information may be found in the online version of this article. Correspondence to: K. Mousavizadeh; e-mail: mousavik@gmail.com tissues, three main factors were determined including appropriate cell sources, carriers for cell delivery such as scaffolds, and osteogenic growth factors.…”

Skin Wound Healing: An Update on the Current Knowledge and Concepts

“…Stem cells or progenitor cells seem to support this process by multiple paracrine effects especially by high levels of pro-angiogenic molecules (i.e., VEGF, HGF, bFGF, EGF, TGF-β, IGF-1) [44,45,46,47]. These effects could be demonstrated in rodent diabetic wounding models, further underscoring the significant activity of stem cells and their potential in repair-resistant chronic wounds [45,46,48,49]. …”

Nanotechnology in Wound Care: One Step Closer to the Clinic

“…7,8 In full-thickness skin defects, the skin barrier is partially compromised, but, due to the abundance of inflammatory cells, phagocytic clearance of nanoparticles is another challenging issue. 9,10 Therefore, innovative surface modification of nanoparticles might allow selective evasion of phagocytic clearance by distinct macrophage phenotypes. 11 The study by Li et al 5 addresses this concern, offering an advanced selective delivery system of lyophilized keratinocyte-targeted nanocarriers loaded with locked nucleic acid (LNA)-modified anti-microRNAs (miRs) that significantly increase Dicer expression and downregulate p21 Waf1/Cip1 expression.…”