γ-PGA hydrogel loaded with cell-free fat extract promotes the healing of diabetic wounds

Aim: To develop an effective strategy for increasing angiogenesis at diabetic wound sites and thereby accelerating wound healing. Materials & methods: A micropatterned nanofibrous scaffold with bioglass nanoparticles encapsulated inside coaxial fibers was prepared by electrospinning. Results: Si ions could be released in a sustained manner from the scaffolds. The hierarchical micro-/nano-structure of the scaffold was found to act as a temporary extracellular matrix to promote endothelial cell adhesion and growth. The scaffold greatly improved angiogenesis and collagen deposition at the wound site, which shortened the healing period of diabetic wounds. Conclusion: This study provides a promising therapeutic option for chronic diabetic wounds with improved angiogenesis.

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Updates in Diabetic Wound Healing, Inflammation, and Scarring

Seminars in Plastic Surgery ◽

10.1055/s-0041-1731460 ◽

2021 ◽

Author(s):

Nina Dasari ◽

Austin Jiang ◽

Anna Skochdopole ◽

Jayer Chung ◽

Edward Reece ◽

...

Keyword(s):

Wound Healing ◽

Disease Process ◽

Wound Dehiscence ◽

Diabetic Patients ◽

Wound Infections ◽

Diabetic Wound ◽

Complex Process ◽

Diabetic Wound Healing ◽

Almost All ◽

Diabetic Wounds

AbstractDiabetic patients can sustain wounds either as a sequelae of their disease process or postoperatively. Wound healing is a complex process that proceeds through phases of inflammation, proliferation, and remodeling. Diabetes results in several pathological changes that impair almost all of these healing processes. Diabetic wounds are often characterized by excessive inflammation and reduced angiogenesis. Due to these changes, diabetic patients are at a higher risk for postoperative wound healing complications. There is significant evidence in the literature that diabetic patients are at a higher risk for increased wound infections, wound dehiscence, and pathological scarring. Factors such as nutritional status and glycemic control also significantly influence diabetic wound outcomes. There are a variety of treatments available for addressing diabetic wounds.

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Extracellular vesicles derived from adipose-derived stem cells accelerate diabetic wound healing by suppressing the expression of matrix metalloproteinase-9

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210719154009 ◽

2021 ◽

Vol 22 ◽

Author(s):

Jiang-wen Wang ◽

Yuan-zheng Zhu ◽

Xuan Hu ◽

Jia-ying Nie ◽

Zhao-hui Wang ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mouse Model ◽

Adipose Derived Stem Cells ◽

Collagen Deposition ◽

Diabetic Wound ◽

Diabetic Wound Healing ◽

Diabetic Wounds ◽

Metalloproteinase 9

Background: The healing of diabetic wounds is poor due to a collagen deposition disorder. Matrix metalloproteinase-9 (MMP-9) is closely related to collagen deposition in the process of tissue repair. Many studies have demonstrated that extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) promote diabetic wound healing by enhancing collagen deposition. Objective: In this study, we explored if ADSC-EVs could downregulate the expression of MMP-9 in diabetic wounds and promote wound healing by improving collagen deposition. The potential effects of ADSC-EVs on MMP-9 and diabetic wound healing were tested both in vitro and in vivo. Methods: We first evaluated the effect of ADSC-EVs on the proliferation and MMP-9 secretion of HaCaT cells treated with advanced glycation end product-bovine serum albumin (AGE-BSA), using CCK-8 western blot and MMP-9 enzyme-linked immunosorbent assay(ELISA). Next, the effect of ADSC-EVs on the healing, re-epithelialisation, collagen deposition, and MMP-9 concentration in diabetic wound fluids was evaluated in an immunodeficient mouse model via MMP-9 ELISA and haematoxylin and eosin, Masson’s trichrome, and immunofluorescence staining for MMP-9. Results: In vitro, ADSC-EVs promoted the proliferation and MMP-9 secretion of HaCaT cells.In vivo, ADSC-EVs accelerated diabetic wound healing by improving re-epithelialisation and collagen deposition and by inhibiting the expression of MMP-9. Conclusion: ADSC-EVs possessed the healing of diabetic wounds in a mouse model by inhibiting downregulating MMP-9 and improving collagen deposition.Thus ,ADSC-EVs are a promising candidate for the treatment of diabetic wounds .

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Platelet-Rich Plasma with Endothelial Progenitor Cells Accelerates Diabetic Wound Healing in Rats by Upregulating the Notch1 Signaling Pathway

Journal of Diabetes Research ◽

10.1155/2019/5920676 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Cheng Zhang ◽

Yu Zhu ◽

Shengdi Lu ◽

Wanrun Zhong ◽

Yanmao Wang ◽

...

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Signaling Pathway ◽

Platelet Rich Plasma ◽

Diabetic Wound ◽

Endothelial Progenitor ◽

Notch1 Signaling ◽

Diabetic Wound Healing ◽

Notch1 Signaling Pathway ◽

Diabetic Wounds

Diabetic wounds, as a kind of refractory wound, are very difficult to heal. Both endothelial progenitor cell (EPC) transplantation and platelet-rich plasma (PRP) can improve diabetic wound healing to some extent. However, PRP application cannot provide reparative cells, while EPC transplantation cannot replenish the required growth factors for wound healing. Thus, when applied alone, neither of these factors is sufficient for effective wound healing. Furthermore, the proliferation, differentiation, and fate of the transplanted EPCs are not well known. Therefore, in this study, we examined the efficacy of combined PRP application with EPC transplantation in diabetic wound healing. Our results indicated that PRP application improved EPC proliferation and migration. The Notch signaling pathway plays a key role in the regulation of the proliferation and differentiation of stem cells and angiogenesis in wound healing. The application of PRP upregulated the Notch pathway-related gene and protein expression in EPCs. Furthermore, experiments with shNotch1-transfected EPCs indicated that PRP enhanced the function of EPCs by upregulating the Notch1 signaling pathway. In vivo studies further indicated that the combination of PRP and EPC transplantation increased neovascularization, reduced wound size, and improved healing in rat wound models. Thus, PRP application can provide the necessary growth factors for wound healing, while EPC transplantation offers the required cells, indicating that the combination of both is a potent novel approach for treating diabetic wounds.

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Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

International Journal of Endocrinology ◽

10.1155/2013/592454 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 26

Author(s):

Chandrama Shrestha ◽

Liling Zhao ◽

Ke Chen ◽

Honghui He ◽

Zhaohui Mo

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Umbilical Cord ◽

Subcutaneous Administration ◽

Conditioned Media ◽

Human Umbilical Cord ◽

Diabetic Wound ◽

Significant Difference ◽

Diabetic Wound Healing ◽

Diabetic Wounds

Objective. Mesenchymal stem cells (MSCs) isolated from the umbilical cord and their conditioned media (CM) can be easily obtained and refined compared with stem cells from other sources. Here, we explore the possibility of the benefits of these cells in healing diabetic wounds.Methodology and Results. Delayed wound healing animal models were established by making a standard wound on the dorsum of eighteen db/db mice, which were divided into three groups with six mice in each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC and their CM significantly accelerated wound closure compared to PBS-treated wounds, and it was most rapid in CM-injected wounds. In day-14 wounds, significant difference in capillary densities among the three groups was noted (n=6;P<0.05), and higher levels of VEGF, PDGF, and KGF expression in the CM- and UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The expression levels of PDGF-βand KGF were higher in CM-treated wounds than those in UC-MSC-treated wounds.Conclusion. Both the transplantation of UC-MSC and their CM are beneficial to diabetic wound healing, and CM has been shown to be therapeutically better than UC-MSC, at least in the context of diabetic wound healing.

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Mesenchymal stem cells correct impaired diabetic wound healing by decreasing ECM proteolysis

Physiological Genomics ◽

10.1152/physiolgenomics.00090.2016 ◽

2017 ◽

Vol 49 (10) ◽

pp. 541-548 ◽

Cited By ~ 13

Author(s):

Junwang Xu ◽

Carlos Zgheib ◽

Maggie M. Hodges ◽

Robert C. Caskey ◽

Junyi Hu ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Protein Content ◽

Collagen I ◽

Extracellular Matrix Protein ◽

Diabetic Wound ◽

Diabetic Wound Healing ◽

Diabetic Wounds

Impaired diabetic wound healing is associated with a dermal extracellular matrix protein profile favoring proteolysis; within the healing diabetic wound, this is represented by an increase in activated matrix metalloproteinase (MMPs). Treatment of diabetic wounds with mesenchymal stem cells (MSCs) has been shown to improve wound healing; however, there has not yet been an assessment of their ability to correct dysregulation of MMPs in diabetic wounds. Furthermore, there has been no prior assessment of the role of microRNA29b (miR-29b), an inhibitory regulatory molecule that targets MMP-9 mRNA. Using in vitro models of fibroblast coculture with MSCs and in vivo murine wound healing models, we tested the hypothesis that MSCs correct dysregulation of MMPs in a microRNA-29b-dependent mechanism. In this study, we first demonstrated that collagen I and III protein content is significantly reduced in diabetic wounds, and treatment with MSCs significantly improves collagen I content in both nondiabetic and diabetic wounds. We then found that MMP-9 gene expression and protein content were significantly upregulated in diabetic wounds, indicating elevated proteolysis. Treatment with MSCs resulted in a decrease in MMP-9 gene expression and protein content level in diabetic wounds 3 and 7 days after wounding. Zymographic analysis indicated that MSC treatment also decreased the amount of activated MMP-9 present in diabetic wounds. Furthermore, miR-29b expression was inversely associated with MMP-9 gene expression; miR-29b expression was decreased in diabetic wounds and diabetic fibroblast. Following treatment of diabetic wounds with MSCs, as well as in diabetic fibroblasts cocultured with MSCs, miR-29b was significantly increased. These findings suggest a potential mechanism through which MSCs enhance diabetic wound healing by improving collagen I content in diabetic wounds through decreasing MMP-9 expression and increasing miR-29b expression.

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A dual functional collagen scaffold coordinates angiogenesis and inflammation for diabetic wound healing

Biomaterials Science ◽

10.1039/d0bm00999g ◽

2020 ◽

Vol 8 (22) ◽

pp. 6337-6349

Author(s):

Ge Long ◽

Dingyang Liu ◽

Xi He ◽

Yeyu Shen ◽

Yannan Zhao ◽

...

Keyword(s):

Wound Healing ◽

Collagen Scaffold ◽

Diabetic Patients ◽

Diabetic Wound ◽

Dual Functional ◽

Persistent Inflammation ◽

Diabetic Wound Healing ◽

Diabetic Wounds ◽

Impaired Angiogenesis

Chronic diabetic wounds, which are associated with persistent inflammation and impaired angiogenesis, occur frequently in diabetic patients.

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Molecular Changes in Diabetic Wound Healing following Administration of Vitamin D and Ginger Supplements: Biochemical and Molecular Experimental Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/4352470 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Hadeel A. Al-Rawaf ◽

Sami A. Gabr ◽

Ahmad H. Alghadir

Keyword(s):

Vitamin D ◽

Wound Healing ◽

Wound Closure ◽

Healing Process ◽

Molecular Targets ◽

Wound Healing Process ◽

Diabetic Wound ◽

Fibrin Deposition ◽

Diabetic Wound Healing ◽

Diabetic Wounds

Background. Circulating micro-RNAs are differentially expressed in various tissues and could be considered as potential regulatory biomarkers for T2DM and related complications, such as chronic wounds. Aim. In the current study, we investigated whether ginger extract enriched with [6]-gingerol-fractions either alone or in combination with vitamin D accelerates diabetic wound healing and explores underlying molecular changes in the expression of miRNA and their predicted role in diabetic wound healing. Methods. Diabetic wounded mice were treated with [6]-gingerol-fractions (GF) (25 mg/kg of body weight) either alone or in combination with vitamin D (100 ng/kg per day) for two weeks. Circulating miRNA profile, fibrogenesis markers, hydroxyproline (HPX), fibronectin (FN), and collagen deposition, diabetic control variables, FBS, HbA1c, C-peptide, and insulin, and wound closure rate and histomorphometric analyses were, respectively, measured at days 3, 6, 9, and 15 by RT–PCR and immunoassay analysis. Results. Treatment of diabetic wounds with GF and vitamin D showed significant improvement in wound healing as measured by higher expression levels of HPX, FN, collagen, accelerated wound closure, complete epithelialization, and scar formation in short periods (11-13 days, (P<0.01). On a molecular level, three circulating miRNAs, miR-155, miR-146a, and miR-15a, were identified in diabetic and nondiabetic skin wounds by PCR analysis. Lower expression in miR-155 levels and higher expression of miR-146a and miR-15a levels were observed in diabetic skin wounds following treatment with gingerols fractions and vitamin D for 15 days. The data showed that miRNAs, miR-146a, miR-155, and miR-15a, correlated positively with the expression levels of HPX, FN, and collagen and negatively with FBS, HbA1c, C-peptide, and insulin in diabetic wounds following treatment with GF and /or vitamin D, respectively. Conclusion. Treatment with gingerols fractions (GF) and vitamin D for two weeks significantly improves delayed diabetic wound healing. The data showed that vitamin D and gingerol activate vascularization, fibrin deposition (HPX, FN, and collagen), and myofibroblasts in such manner to synthesize new tissues and help in the scar formation. Accordingly, three miRNAs, miR-155, miR-146a, and miR-15, as molecular targets, were identified and significantly evaluated in wound healing process. It showed significant association with fibrin deposition, vascularization, and reepithelialization process following treatment with GF and vitamin D. It proposed having anti-inflammatory action and promoting new tissue formation via vascularization process during the wound healing. Therefore, it is very interesting to consider miRNAs as molecular targets for evaluating the efficiency of nondrug therapy in the regulation of wound healing process.

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Nanofiber/hydrogel Core-shell Scaffolds With Three-dimensional Multilayer Patterned Structure for Accelerating Diabetic Wound Healing

10.21203/rs.3.rs-952440/v1 ◽

2021 ◽

Author(s):

Jiankai Li ◽

Tianshuai Zhang ◽

Mingmang Pan ◽

Feng Xue ◽

Fang Lv ◽

...

Keyword(s):

Wound Healing ◽

Three Dimensional ◽

Vapor Permeability ◽

Core Shell ◽

Diabetic Wound ◽

3D Network ◽

Diabetic Wound Healing ◽

Diabetic Wounds

Abstract Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Herein, a nanofiber/ hydrogel core-shell scaffold with three-dimensional (3D) multilayer patterned structure (3D-PT-P/GM) was introduced for promoting diabetic wound healing with improved angiogenesis. The results showed that the 3D-PT-P/GM scaffolds possessed multilayered structure with interlayer spacing of about 15-80 μm, and the hexagonal micropatterned structures were uniformly distributed on the surface of each layer. The nanofibers in the scaffold exhibited distinct core-shell structures with Gelatin methacryloyl (GelMA) hydrogel as the shell and Poly (D, L-lactic acid) (PDLLA) as the core. The results showed that the porosity, water retention time and water vapor permeability of the 3D-PT-P/GM scaffolds increased to 1.6 times, 21 times, and 1.9 times than that of the two-dimensional (2D) PDLLA nanofibrous scaffolds, respectively. The in vitro studies showed that the 3D-PT-P/GM scaffolds could significantly promote cell adhesion, proliferation, infiltration and migration throughout the scaffolds, and the expression of cellular communication protein-related genes, as well as angiogenesis-related genes in the same group, was remarkably upregulated. The in vivo results further demonstrated that the 3D-PT-P/GM scaffolds could not only effectively absorb exudate and provide a moist environment for the wound sites, but also significantly promote the formation of a 3D network of capillaries. As a result, the healing of diabetic wounds was accelerated with enhanced angiogenesis, granulation tissue formation, and collagen deposition. These results indicate that nanofiber/ hydrogel core-shell scaffolds with 3D multilayer patterned structures could provide a new strategy for facilitating chronic wound healing.

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Nanotechnology-based Therapeutic Applications: In Vitro, In Vivo Clinical Studies for Diabetic Wound Healing

Biomaterials Science ◽

10.1039/d1bm01211h ◽

2021 ◽

Author(s):

Sheikh Tanzina Haque ◽

Subbroto Kumar Saha ◽

Md. Enamul Haque ◽

Nirupam Biswas

Keyword(s):

Wound Healing ◽

Side Effects ◽

Conventional Treatment ◽

Treatment Modalities ◽

Diabetic Wound ◽

Chronic Complications ◽

Diabetic Wound Healing ◽

Diabetic Wounds

Diabetic wounds often presage chronic complications that are difficult to treat. Unfortunately, existing conventional treatment modalities often warrant unpremeditated side effects, given the need to develop alternative therapeutic phenotypes that...

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