Wound Healing In Diabetic Rats Research Articles

Preparation of novel berberine nano-colloids for improving wound healing of diabetic rats by acting Sirt1/NF-κB pathway

In the present work, novel berberine nano-colloids hydrogel (BNH) was prepared for improving wound healing of diabetic rats. Polyvinyl alcohol (PVA), sodium alginate (Alg) were adopted as building blocks to form BNH. Calcium ions was used as crosslink agent to construct BNH. The skin injury model of diabetic rats was successfully established, and the prepared hydrogel was applied to the wound. Animal experiments proved that BNH could promote wound healing of diabetic rats. Further molecular mechanism research revealed that BNH could inhibit the expression of NF-κB, TNF-a and IL-6, but increase the expression of F VEGF, CD 31 and SMA by activating Sirt 1 which were benefit for wound healing of diabetic rats.

Effect of hyaluronic acid on skin healing in diabetic rats

Purpose: The objective of this study was to examine the effect of topical hyaluronic acid (HA) treatment on wound healing in diabetic rats. Methods: Wistar rats weighing 279 ± 32g were randomly selected and allocated into 2 groups, with six rats each, all submitted to diabetes induction with streptozotocin. Under anesthesia, a 1 cm2 open wound was made on the back skin of all animals. Group 1 - rats treated with topical 0.9% saline use on open skin wounds. Group 2 - rats treated with topical use of 0.4% HA over skin lesions. After anesthesia on the 10th postoperative day, a biopsy of the skin dorsal wound area, including the entire healing wound, was performed for histopathological examination. Quantitative analysis was performed for the amount of macrophages, vascular neoformation, fibroblasts and collagen fibers, using a digitizer and image analyzer system. Results: All animals included in the study had blood glucose above 250mg/dL on the second day after streptozotocin administration and remained with high blood glucose until the 10th day, when the study was completed. After quantitative evaluation of collagen fibers, fibroblasts, vascular neoformation and macrophages performed in the ImagePro Plus 6.0 software, it was observed that the wound scores of diabetic animals treated with hyaluronic acid (185 ± 15.7) were significantly higher than those treated with saline (134 ± 11.7). The difference was statistically significant (p <0.05). Conclusion: Treatment of open wounds with HA effectively improved the healing process in hyperglycemic rats through an anti-inflammatory effect. This study suggests and provided evidence that topical use of HA is promising in the treatment of wounds in diabetic rats.

Impact of Photobiomodulation and Condition Medium on Mast Cell Counts, Degranulation, and Wound Strength in Infected Skin Wound Healing of Diabetic Rats.

Background: Numerous people suffer from diabetes mellitus (DM) and resultant diabetic foot ulcers (DFU), which lack effective treatment. Photobiomodulation (PBM) has accelerated wound healing in diabetic animals and patients in some studies. However, there is scant information on the number and activation state of skin mast cells (MCs) in PBM-treated diabetic wounds. Objective: We intend to assess the influence of the number of MCs and degranulation in the remodeling step of an infected wound model on wound strength and its microbial flora in a type 1 DM (T1DM) rat model by administration of PBM, condition medium (CM) derived from human bone marrow mesenchymal stem cells (hBMMSCs), and the combination of PBM+CM. Methods: We prepared CM by culturing hBMMSCs. T1DM was induced in 72 rats and, after 1 month, we created one excisional wound in each rat. All wounds were infected with methicillin-resistant Staphylococcus aureus (MRSA). We divided the rats into four groups: (n = 18): (i) control; (ii) PBM; (iii) CM, and (iv) PBM+CM. On days 4, 7, and 15, we conducted microbiological, tensiometrical, and stereological analyses. The type of MCs (T1MCs, T2MCs, or T3MCs) and total number of MCs (TOMCs) were counted by light microscopy. Results: On day 15, the PBM+CM, PBM, and CM groups had significantly increased wound strength compared with the control group. There was a significant decrease in colony-forming units (CFU) at all time points in the PBM+CM and PBM groups. The PBM+CM and PBM groups had more stable MCs (T1MCs), less significant degranulated MCs (T2MCs), less significant disintegrated MCs (T3MCs), and less significant TOMCs compared with the control group at all time points. Conclusions: PBM+CM and PBM treatments significantly increased the healing process in an ischemic and MRSA-infected wound model of T1DM rats. PBM+CM and PBM significantly decreased both TOMCs and their degranulation, and significantly decreased CFU.

Conditioned medium from 3D culture system of stromal vascular fraction cells accelerates wound healing in diabetic rats.

Aim: We investigated the healing effects of conditioned medium (CM) derived from a physiological 3D culture system engineered to use an extracellular matrix/stromal vascular fraction (SVF) gel enriched for adipose on diabetic wounds in rats. This CM (Gel-CM) was compared with that from a 2D culture system that used SVF cells (SVF-CM). Materials & methods: Keratinocytes, fibroblasts and wounds were treated with Gel-CM and SVF-CM, and cytokine levels in the CM types were quantified. Results: Proliferation and migration of keratinocytes and fibroblasts were significantly higher after treatment with Gel-CM than with SVF-CM. Collagen secretion by fibroblasts and wound closure were highly stimulated by Gel-CM. Proteomic analyses revealed a higher concentration of growth factors in Gel-CM than in SVF-CM. Conclusion: Gel-CM is a promising therapeutic option for treating diabetic wounds.

Low-frequency ultrasound enhances vascular endothelial growth factor expression, thereby promoting the wound healing in diabetic rats.

Diabetes is a chronic metabolic disease with a high prevalence worldwide, which typically delays or impairs wound healing, potentially causing death. Low-frequency ultrasound treatment promotes the repair of various injuries and may promote wound healing. The aim of the present study was to determine whether low-frequency ultrasound can accelerate wound healing, as well as investigate its effects on the expression of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in diabetic rats. A total of 45 Wistar rats were intraperitoneally injected with 1% streptozocin following intraperitoneal injection of pentobarbital sodium anesthesia. Subsequently an incision wound was created in the skin of back. The area of the wound was recorded to calculate the rate of wound healing. The expression of VEGF and TGF-β1 was determined via immunohistochemical analysis and their mRNA and protein levels were measured via reverse transcription-quantitative PCR analysis. The results revealed that when compared with the control group, low-frequency ultrasound treatment significantly increased wound healing rate in diabetic rats and markedly increased the mRNA and protein levels of VEGF and TGF-β1. US treatment also reduced the mRNA and protein levels of TNF-α and IL-6. In conclusion, the results of the present study indicated that low-frequency ultrasound promotes the expression of VEGF and TGF-β1, and inhibits the expression of IL-6 and TNF-α, thereby promoting wound healing in diabetic rats.

Preliminary evaluation and mechanism of adipose-derived stem cell transplantation from allogenic diabetic rats in the treatment of diabetic rat wounds

Preliminary evaluation and mechanism of adipose-derived stem cell transplantation from allogenic diabetic rats in the treatment of diabetic rat wounds

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

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.

Acceleration of wound healing activity with syringic acid in streptozotocin induced diabetic rats

Impaired wound healing is a serious concern of uncontrolled hyperglycemia that can lead to gangrene, and even death. There is an urgent need to look for better alternative therapy because of the undesirable side effects of currently available synthetic drugs in the market. Syringic acid (SA) is a natural phenolic compound abundantly available in edible fruits and plants. In this study, wound healing activities of 2.5% and 5.0% SA were evaluated in type 2 diabetic rats using incisional wound model. SA-treated diabetic wounds showed faster rate of wound closure and epithelization with enhanced contents of hydroxyproline and protein compared to diabetic wounds. SA effectively prevents alterations in blood glucose levels, serum insulin and dyslipidemia in diabetic wound rats. The SA-treated diabetic wounds after 14 days of treatment demonstrated inhibition of pro-inflammatory response (NF-κB p65, TNF-α, IL-1β, IL-8 and IL-2) with improvement in anti-inflammatory response (IL-10), inhibited the elevated oxidative stress and decreased the concentrations of matrix metalloproteinases (MMP-2, −8 and −9) and increased the concentrations of TIMP-1 & TIMP- 2. Furthermore, the diabetic wounds were presented with an increase in expression of CD 31 and 68, growth factors (TGF-β1, collagen-I and α-SMA and VEGF) with significant improvement in collagen deposition, re-epithelialization and complete skin structure as revealed by histological analysis after treatment of diabetic wounds with SA for 14 days. Hence, the results of this study designate that SA significantly improves wound healing in diabetic rats and could be used as a potential therapy for treatment of diabetic wounds.

Human keratinocyte-derived microvesicle miRNA-21 promotes skin wound healing in diabetic rats through facilitating fibroblast function and angiogenesis.

Skin wound healing is a complex physiological process that maintains the integrity of the skin tissues, involving a variety of distinct cell types and signaling molecules. The specific signaling pathways or extracellular cues that govern the healing processes remain elusive. Microvesicles (MVs) have recently emerged as critical mediators of cell communication by delivery of genetic materials to target cells. In this study, we found the direct delivery of HEKa-MVs expressing miR-21 mimics significantly promoted the healing of skin wound in diabetic rats. In-depth studies showed that MV miR-21 promoted fibroblast migration, differentiation, and contraction, induced a pro-angiogenic process of endothelial cells and mediated a pro-inflammatory response. Mechanically, MV miR-21 might target specific essential effector mRNA in fibroblasts such as MMP-1, MMP-3, TIMP3, and TIMP4 to increase MMPs expression and enzymatic activities. Moreover, MV miR-21 regulated ɑ-SMA and N-cadherin to induce fibroblast-myofibroblast differentiation. MV miR-21 up-regulated the IL-6 and IL-8 expressions and their secretion to amplify the immune response. Furthermore, MV miR-21 down-regulated PTEN and RECK in protein level, and activate MAPK/ERK signaling cascade, thereby promoting fibroblast functions. Thus, our study has provided for the first time the basis for the potential application of HEKa-MVs, and MV miR-21 in particular for wound healing.

Hemin attenuated oxidative stress and inflammation to improve wound healing in diabetic rats

Oxidative stress and persistent inflammation play crucial role in the progression of diabetic wound complications. Hemeoxgenase-1 (HO-1) by degrading hemin has been shown to display anti-oxidant and anti-inflammatory effects. Further, hemin is a potent HO-1 inducer. Thus, the current study was aimed to evaluate the effect of topical application of hemin on diabetic wound in rats. Four hundred square millimeter open excision wound were created 2weeks after induction of diabetes with single intraperitoneal injection of streptozotocin (60mg/kg), and the diabetic rats were divided into three groups namely diabetic control, hemin, and tin protoporphyrin (SnPPIX). Ointment base, hemin (0.5% in ointment base), and SnPPIX (0.5% in ointment base) were applied topically to wounded area in diabetic control, hemin, and SnPPIX group rats, respectively, twice daily for 19days. Hemin significantly increased the wound contraction in comparison to control and SnPPIX-treated rats. Time-dependent analysis revealed significant increase in anti-oxidants with concomitant decrease in oxidants in hemin-treated rats as compared to diabetic control rats. Further, mRNA expression decreased for inflammatory cytokine and increased for anti-inflammatory cytokine in hemin group as compared to diabetic control rats. Expression of HO-1 also increased in hemin group as compared to diabetic control rats. However, SnPPIX group results were in disagreement with results of hemin which is clearly reflected in histopathology. Results indicate the ability of hemin to accelerate wound healing in diabetic rats by combating inflammation and oxidative stress probably via HO-1.

Addition of 2-deoxy-d-ribose to clinically used alginate dressings stimulates angiogenesis and accelerates wound healing in diabetic rats.

Following recent work from our group on a small ribose-derived sugar 2-deoxy-d-ribose which stimulates angiogenesis in a chick chorionic allantoic membrane bioassay and in skin wounds in healthy rats, we tested the effect of this sugar when added to a common alginate wound dressing in a well-accepted diabetic skin wound model in rats. Dressings were simply loaded with filter-sterilized sugar solutions that were proved stable at room temperature for at least two weeks. Prior to undertaking the animal study, we assessed in vitro release of sugar loaded from alginate dressings loaded with either 5 or 10% 2-deoxy-d-ribose. Both showed more than 90% release of sugar over three days followed by a lesser and sustained release for up to eight days. Diabetes was induced in rats by streptozotocin injection followed by confirmation through measuring elevated blood glucose levels all over the period of the study. Full thickness skin wounds of 20 mm diameter showed slow healing and were still unhealed at 20th day in the control animals. The addition of alginate hydrogel did significantly stimulate wound healing compared to the untreated animals, but the addition of 2-deoxy-d-ribose at either 5 or 10% further and significantly improved the rate of wound healing. The most striking result was seen in the effect of sugar on angiogenesis in the wound beds where alginate alone did not improve the extent of CD34 identified blood vessels in the wound beds but the addition of sugar significantly increased these – this could be seen as early as seven days post addition of the sugar-loaded alginate dressing and was still evident at day 20. Thus, these results suggest that the controlled use of 2-deoxy-d-ribose could be a novel and cost-effective therapy for the management of impaired wound healing in diabetic patients.

Lecithin-based deferoxamine nanoparticles accelerated cutaneous wound healing in diabetic rats

Nanoparticles have higher frequency of being exposed to cells or tissue, and are thus more likely to gain access into cytoplasm or nuclei to modulate molecular events due to significantly larger surface area to volume ratio. As a result, they present amplified response or even different physiochemical and biomedical properties from bigger particles. Deferoxamine accelerates wound healing in diabetic rats by increased neovascularization, reduced inflammation and improved maturation of wound. We investigated the wound healing potential of deferoxamine-nanoparticles in diabetic rats. Lecithin based nanoparticles of deferoxamine were prepared and characterized. The diabetic rats were divided into five Groups, of which Group I was treated with pluronic-gel f-127 (25%), Group II with deferoxamine 0.1% and Group III, IV and V were treated with deferoxamine-nanoparticles incorporated in pluronic-gel f-127 25% at 0.03% (0.01% deferoxamine), 0.1% (0.03% deferoxamine) and 0.3% (0.1% deferoxamine) w/v respectively. The wound closure was significantly accelerated in group V as compared to control groups. HIF-1α, VEGF, SDF-1α, TGF-β1, and IL-10 protein levels were significantly higher in group V. The collagen deposition and neovascularization was greater in deferoxamine-nanoparticle treated rats. In contrast, TNF-α level was lowest in group V. In summary, the deferoxamine-nanoparticle formulation we developed, when applied topically on diabetic wounds results in faster wound healing as compared to simple deferoxamine formulation. This formulation may prove to be an effective therapy for treatment of diabetic wounds.

Erratum to "Mesenchymal Stem Cells Coated by the Extracellular Matrix Promote Wound Healing in Diabetic Rats".

[This corrects the article DOI: 10.1155/2019/9564869.].

639-P: Pharmacological Mobilization and Recruitment of Bone Marrow Stem Cells Accelerates Diabetic Wound Healing in Rats with Diabetic Complications

Introduction: The lifetime incidence of foot ulcers has been estimated to be 19% to 34% among persons with diabetes. Diabetic wound healing(DWH) remains a challenge. Given the promising role of stem cells in wound healing, the current study proposed to improve DWH by mobilizing and recruiting bone marrow stem cells pharmacologically with combination of AMD3100 and low-dose FK506 (AF) in rats. Methods: T2 GK rats and STZ induced T1DM SD rats were used. To determine the role of bone marrow stem cells, bone marrow from GFP tg Lewis were transplanted into wt Lewis rats and T1 rats were induced by STZ injection at 2 months following bone marrow transplantation. Full-thickness wounds were created in the dorsal skin or in the foot skin at 6 weeks after STZ injection or GK rats at 4 month old. Wounded rats were divided into two experimental groups and received saline or a combination of AMD3100 (1mg/kg) and FK506 (0.1mg/kg) immediately after wounding and every 2 days until complete healing. Results: At the time of wounding, all animals developed peripheral artery disease and neuropathy. The back wound healing time was reduced from 27 to 19 days and the foot wound healing time was reduced from 25 to 20 days in T1DM rats treated with AF. Similarly, the back wound healing time was reduced from 26(S) to 21(AF) days in GK rats. Equally important, healing was accompanied by reduced scar and regeneration of hair follicles. Searching for the mechanisms, we found that AF therapy mobilized bone marrow stem cells to peripheral blood and recruited bone marrow-derived CD31+CD133+ endothelial progenitor cells, CD34+ stem cells and Ym1/2+ M2 macrophages into the wound sites and enhanced capillary and hair follicle neogenesis. Conclusion: Combination of AMD3100 and low-dose FK506 results in better and faster healing of diabetic wounds in rats with diabetic peripheral artery disease and neuropathy. Our findings offer a significant therapeutic approach to healing of DFU. Disclosure L. Qi: None. A.R. Ahmadi: None. J. Huang: None. Q. Lin: None. M. Chen: None. H. Kuwabara: None. K. Iwasaki: None. J. Burdick: None. Z. Sun: None.

Propranolol regulates ERK1/2 signaling pathway and promotes chronic wound healing in diabetic rats.

This study aimed to investigate if propranolol could regulate ERK1/2 signaling pathway and promote chronic wound healing in diabetic rats. Twenty-two rats were used to establish a diabetic chronic wound animal model. They were randomly separated into two groups: the propranolol group and the control group. The propranolol group was treated with propranolol ointment and the control group was treated with propranolol matrix cream to cover the wound surface. The expression of the p-ERK1/2 protein was detected by the Western Blot. RT-qPCR was used to detect the expression of VEGF. The concentrations of IL-6 and TNF-α were detected by ELISA. The body weight of rats was significantly reduced after type 2 diabetes mellitus modeling. The healing rate of rats in the control group was significantly lower than that in the propranolol group (p<0.05). There was a significant increase in the expression of the p-ERK1/2 protein in the wound tissue of the propranolol group compared with that in the control group, except for the 11th day (p<0.05). The relative expression of Vascular Endothelial Growth Factor (VEGF) in the propranolol group was significantly higher than that in the control group on the 2nd day (p<0.05), while the relative expression of VEGF in the propranolol group was significantly increased on the 11th day after modeling (p<0.05). On the 20th day, the expressions of IL-6 and TNF-α in the propranolol group were significantly higher than those in the control group, and there were significant differences (p<0.05). It was found that the IL-6 and TNF-α expressions in the propranolol group reached the peak on the 11th day and then gradually decreased (p<0.05). The results indicated that propranolol can accelerate the healing of diabetic wounds by regulating the expression of VEGF by phosphorylation of ERK1/2 protein, thus promoting chronic wound healing in diabetes.

Amygdalin improves burn wound healing in diabetic rats

IntroductionThe skin has a unique plasticity and regenerative abilities which are partly impaired in diabetics. On the other hand, amygdalin or vitamin B17 has an array of functions affecting inflammation and cell regeneration.AimThis study aimed to assess the effect of amygdalin on burn wound healing in diabetic ratsMaterials and methodsSixty‐four male Sprague‐Dawley rats were subjected to burn according to standard published models. Diabetes was induced by sterptozocin and treatment by vitamin B17 followed every other day for 28 days, the duration of the experiment. Biopsies were taken on days 1, 3, 7, 14, and 28 for light microscopy evaluation and cytokines modulation.ResultsHistological assessment of the burn wounds showed a remarkable improvement in earlier healing, smaller wound area and a better scar in the amygdalin treated group. In addition, a significant decrease in the inflammatory cytokines (IL‐1α, Il‐6 and IL‐12) was noted.ConclusionAmygdalin improved burn wound healing in diabetic rats, in quality and time.Support or Funding InformationPh D Program (University of Palermo and American University of Beirut)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Topical Application of Lactobacillus plantarum on Burn Wound Healing in Diabetic Rats

Objective- This study was designed to investigate the effect of Lactobacillus plantarum gel on cutaneous burn wound healing in diabetic rats.Design- Randomized experimental studyAnimals- Forty adult male ratsProcedures- Two circular 1 cm cutaneous wounds were created in the dorsum back of each rat. 48 h post-burning, debridement with a 1 cm biopsy punch was performed. The wounds were divided into the following four treatment groups (n= 10, each): 1. Untreated or negative control (NC), 2. silver sulfadiazine (positive control-SSD), 3. base gel (BG) 4. Lactobacillus plantarum Gel (LP gel). The wound surface area and epithelialization were monitored. The animals were euthanized at 10 (n = 5), and 20 (n = 5) days post-injury (DPI) and the skin samples were used for histopathological, biochemical, TGF-β gene expression and biomechanical investigations. Results- It was indicated that the L. plantarum and SSD treated lesions had the lowest percentage of wound size and collagen content and also the L. plantarum treated group showed shortest inflammatory period and highest amount of TGF-β at 10 days post injury. The L. plantarum gel treated lesions also demonstrated greater ultimate load compared to the untreated and based gel treated wounds.Conclusions and Clinical Relevance- In conclusion, L. plantarum gel therapy improved wound healing and resulted in better outcomes after severe burn injury in diabetic rats compared with the silver sulfadiazine treatment.

Roxadustat promotes angiogenesis through HIF-1α/VEGF/VEGFR2 signaling and accelerates cutaneous wound healing in diabetic rats.

Diabetic foot ulcers are a major health-care burden worldwide. One primary cause of the delayed wound healing in diabetic patients is impaired function of the hypoxia-inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) axis, which results in compromised neovascularization in response to hypoxia. In the present study, we aimed to investigate the effect of roxadustat, a novel HIF prolyl-4-hydroxylase inhibitor, on angiogenesis and its therapeutic effect on cutaneous wound healing in diabetic rats. In vitro, we found that roxadustat could promote the angiogenic activity of human umbilical vein endothelial cells, accompanied by up-regulation of HIF-1α/VEGF/VEGFR2 signaling. Next, we demonstrated that Ki8751, a VEGFR2-specific inhibitor, could inhibit the increased angiogenic activity of human umbilical vein endothelial cells induced by roxadustat. In vivo, we performed a Matrigel plug assay and demonstrated that roxadustat induced vascularization of the Matrigel plugs, and this effect could be partially inhibited by Ki8751. Finally, we utilized a streptozotocin-induced diabetic rat model and found that roxadustat could accelerate cutaneous wound healing and promote angiogenesis in the wound sites. In conclusion, roxadustat promotes angiogenesis via activation of the HIF-1α/VEGF/VEGFR2 pathway and exhibits therapeutic effects on diabetic wound healing by increasing angiogenesis. Our findings suggest that roxadustat can be a promising strategy to promote diabetic cutaneous wound healing.

Human umbilical cord mesenchymal stem cells implantation accelerates cutaneous wound healing in diabetic rats via the Wnt signaling pathway

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.

Mesenchymal Stem Cells Coated by the Extracellular Matrix Promote Wound Healing in Diabetic Rats.

Objective To investigate the effects of mesenchymal stem cells (MSCs) coated by the extracellular matrix (ECM) on wound healing in diabetic rats. Methods Mesenchymal stem cells were cocultured with ECM. Cell viabilities were evaluated using MTT assay. The diabetes model was established using both STZ and high-glucose/fat methods in SD rats. A wound area was made on the middle of the rats' back. MSCs or ECM-MSCs were used to treat the rats. HE staining and CD31 immunohistochemistry were used to detect the skin thickness and angiogenesis. Western blotting and qRT-PCR were conducted to determine the level of VEGF-α, PDGF, and EGF. Results It was observed that treatment of ECM had no significant effects on the cell viability of ECM-MSCs. Wound area assay showed that both MSCs and ECM-MSCs could enhance the wound healing of diabetic rats and ECM-MSCs could further promote the effects. Both MSCs and ECM-MSCs could enhance angiogenesis and epithelialization of the wounds, as well as the expression of VEGF-α, PDGF, and EGF in wound tissues, while ECM-MSC treatment showed more obvious effects. Conclusion Mesenchymal stem cells coated by the extracellular matrix could promote wound healing in diabetic rats. Our study may offer a novel therapeutic method for impaired diabetic wound healing.