Diabetic Skin Ulcers Research Articles

Autophagy and skin wound healing.

Autophagy is a lysosome-dependent, self-renewal mechanism that can degrade and recycle cellular components in eukaryotic cells to maintain the stability of the intracellular environment and the cells ability to cope with unfavorable environments. Numerous studies suggest that autophagy participates in regulating various cellular functions and is closely associated with the onset and progression of various diseases. Wound healing is a complex, multistep biological process that involves multiple cell types. Refractory wounds, which include diabetic skin ulcers, can seriously endanger human health. Previous studies have confirmed that autophagy plays an essential role in various phases of wound healing. Specifically, in the inflammatory phase, autophagy has an anti-infection effect and it negatively regulates the inflammatory response, which prevents excessive inflammation from causing tissue damage. In the proliferative phase, local hypoxia in the wound can induce autophagy, which plays a role in anti-apoptosis and anti-oxidative stress and promotes cell survival. Autophagy of vascular endothelial cells promotes wound angiogenesis and that of keratinocytes promotes their differentiation, proliferation and migration, which is conducive to the completion of wound re-epithelialisation. In the remodeling phase, autophagy of fibroblasts affects the formation of hypertrophic scars. Additionally, a refractory diabetic wound may be associated with increased levels of autophagy, and the regulation of mesenchymal stem cell autophagy may improve its application to wound healing. Therefore, understanding the relationship between autophagy and skin wound healing and exploring the molecular mechanism of autophagy regulation may provide novel strategies for the clinical treatment of wound healing.

Angiogenic efficacy of ASC spheroids filtrated on porous nanosheets for the treatment of a diabetic skin ulcer.

Stem cell transplantation is expected to be an effective treatment for intractable skin ulcers by promoting angiogenesis; however, it is challenging to quickly realize a sufficient bloodstream for the ulcers. For this treatment, sheet-like materials with monolayer cells such as cell sheets have been investigated. However, they have a limitation of cell number that can be transplanted at one time due to the two-dimensional, monolayer cell structure, and sufficient secretion of growth factors cannot be expected. In this regard, cellular aggregates, such as spheroids, can reproduce three-dimensional cell-cell interactions that cause biological functions of living tissues more representative than monolayer cells, which is important to achieving efficient secretion of growth factors. In this study, we focused on free-standing porous polymer ultrathin films ("porous nanosheets") comprising poly(d,l-lactic acid) (PDLLA) and succeeded in developing a spheroid-covered nanosheet, on which more than 1000 spheroids from adipose-tissue derived stem cells (ASCs) were loaded. The porous structure with an average pore diameter of 4 μm allowed for facile filtration and carrying spheroids on the nanosheet, as well as sufficient oxygen and nutrients inflow to the cells. The spheroid-covered nanosheet achieved homogeneous transference of spheroids to a whole skin defect in diabetic model mice. Given the continuous release of vascular endothelial growth factor (VEGF) from the spheroids, the transplanted spheroids promoted healing with more accelerated angiogenesis than a nanosheet with a monolayer of cells. The spheroid-covered nanosheet may be a new regenerative material for promoting intractable skin ulcer healing.

Meta-Analysis of the Effect of Kangfuxin Liquid on Diabetic Patients with Skin Ulcers.

In this study, we used meta-analysis to comprehensively evaluate the clinical efficacy of Kangfuxin Liquid in the treatment of diabetic patients with skin ulcers. Literature search was performed through PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang Data. The retrieval was not limited by language, and the search period was from 2010 to October 12, 2020. Diabetic patients with skin ulcers were treated with Kangfuxin Liquid combined with basic treatment as the treatment group and only basic treatment as the control group. Stata16.0 software was used for system evaluation. A total of 11 studies and 874 patients were included. Meta-analysis showed that 11 studies compared the treatment efficacy between the two groups, and the results showed that the treatment efficacy in the treatment group was significantly higher than that in the control group [OR = 5.38, 95% CI (3.52, 8.24), P < 0.001]. Among them, 9 studies compared the healing time of wounds. The healing time of the treatment group was significantly longer than that of the control group [SMD = −2.13, 95% CI (−2.85, −1.41), P < 0.001]. Five studies compared the length of stay, and the length of stay in the treatment group was shorter than that in the control group [SMD = −3.68, 95% CI (−5.38, −1.97), P < 0.001]. Compared with basic treatment, Kangfuxin Liquid combined with basic treatment has an ideal effect in the treatment of diabetic skin ulcers, which can improve the overall treatment efficiency and shorten the wound rehabilitation time and the length of stay.

Nanotechnology in the Treatment of Diabetic Complications: A Comprehensive Narrative Review.

In today's society, the prevention and treatment of diabetes mellitus and its subsequent complications have brought trouble to human beings. Complications caused by diabetes bring not only physical and mental pain to patients but also a heavy economic burden to families. And once diabetic complications occur, they are often irreversible and very difficult. At present, some studies suggest that nanotechnology can treat some diabetic complications. This paper reviews the application of nanotechnology in the repair of diabetic segmental bone injury, the healing of diabetic skin ulcers, the therapeutic effect, and improvement strategies and deficiencies of nanotechnology in diabetic complications.

Research advances on the characteristics and wound healing promoting effect of in-situ forming injectable hydrogels

Research of in-situ induced repair and regeneration is a multi- and inter-disciplinary field, which is of important potentials in the treatment of both large-area deep burns and chronic wounds such as diabetic skin ulcers. In-situ forming injectable hydrogels which are hydrogel-like biomaterials that can spontaneously gelatinize in physiological condition when applied in local wounds have been explored in recent years. This kind of biomaterials contain extracellular matrix, in which cells promoting wound repairing can be added if required, and can work as release-controlled carriers for active peptides such as growth factors to simulate local wound microenvironment and induce the repair and regeneration. Herein, characteristics and function of promoting wound repair and regeneration about in-situ forming injectable hydrogels were reviewed, including material types and their relevant working mechanisms, advantages, existing problems, etc.

Electrospun and co-electrospun biopolymer nanofibers for skin wounds on diabetic patients: an overview.

Wound healing treatment in diabetic patients worldwide represents around 2.1 trillion dollars to global health sectors. This is because of the complications presented in the wound healing process of skin ulcers, such as a lack of macrophage and fibroblast growth factors (TGF-β1 and PDGF, respectively) that are both needed for extracellular matrix (ECM) synthesis. Therefore, there is a need for research on new and cost-effective materials to enable ECM synthesis. Such materials include co-electrospun nanofibers used as wound dressings, since they have a similar morphology to the ECM, and therefore, possess the advantage of using different materials to accelerate the wound healing process. Co-electrospun nanofibers have a unique structural configuration, formed by a core and a shell. This configuration allows the protection and gradual liberation of healing agent compounds, which could be included in the core. Some of the materials used in nanofibers are polymers, including natural compounds, such as chitosan (which has been proven to possess antimicrobial and therapeutic activity) and gelatin (for its cell growth, adhesion, and organisational capacity in the wound healing process). Synthetics such as polyvinyl-alcohol (PVA) (mainly as a co-spinning agent to chitosan) can also be used. Another bioactive compound that can be used to enhance the wound healing process is eugenol, a terpenoid present in different medicinal plant tissues that have scarring properties. Therefore, the present review analyses the potential use of co-electrospun nanofibers, with chitosan–PVA–eugenol in the core and gelatin in the shell as a wound dressing for diabetic skin ulcers.

Improving Chronic Diabetic Wound Healing through an Injectable and Self-Healing Hydrogel with Platelet-Rich Plasma Release.

Diabetic skin ulcer is one of the severe complications of diabetes mellitus, which has a high incidence and may cause death or disability. Platelet-rich plasma (PRP) is widely used in the treatment of diabetic wounds due to the effect of growth factors (GFs) derived from it. However, the relatively short half-life of GFs limits their applications in clinics. In addition, the presence of a large amount of proteases in the diabetic wound microenvironment results in the degradation of GFs, which further impedes angiogenesis and diabetic wound healing. In our study, we fabricated a self-healing and injectable hydrogel with a composite of chitosan, silk fibroin, and PRP (CBPGCTS-SF@PRP) for promoting diabetic wound healing. CBPGCTS-SF@PRP could protect PRP from enzymatic hydrolysis, release PRP sustainably, and enhance the chemotaxis of mesenchymal stem cells. The results showed that it could promote the proliferation of repair cells in vitro. Moreover, it could enhance wound healing by expediting collagen deposition, angiogenesis, and nerve repair in a type 2 diabetic rat model and a rat skin defect model. We hope that this study will offer a new treatment for diabetic nonhealing wounds in clinics.

Use of Machine Learning Approaches in Clinical Epidemiological Research of Diabetes

Machine learning approaches-which seek to predict outcomes or classify patient features by recognizing patterns in large datasets-are increasingly applied to clinical epidemiology research on diabetes. Given its novelty and emergence in fields outside of biomedical research, machine learning terminology, techniques, and research findings may be unfamiliar to diabetes researchers. Our aim was to present the use of machine learning approaches in an approachable way, drawing from clinical epidemiological research in diabetes published from 1 Jan 2017 to 1 June 2020. Machine learning approaches using tree-based learners-which produce decision trees to help guide clinical interventions-frequently have higher sensitivity and specificity than traditional regression models for risk prediction. Machine learning approaches using neural networking and "deep learning" can be applied to medical image data, particularly for the identification and staging of diabetic retinopathy and skin ulcers. Among the machine learning approaches reviewed, researchers identified new strategies to develop standard datasets for rigorous comparisons across older and newer approaches, methods to illustrate how a machine learner was treating underlying data, and approaches to improve the transparency of the machine learning process. Machine learning approaches have the potential to improve risk stratification and outcome prediction for clinical epidemiology applications. Achieving this potential would be facilitated by use of universal open-source datasets for fair comparisons. More work remains in the application of strategies to communicate how the machine learners are generating their predictions.

Intravenous Injection of Muse Cells as a Potential Therapeutic Approach for Epidermolysis Bullosa

Intravenous Injection of Muse Cells as a Potential Therapeutic Approach for Epidermolysis Bullosa

NMR-based metabolomic analysis for the effects of Huiyang Shengji extract on rat diabetic skin ulcers

Ethnopharmacological relevanceHuiyang Shengji formula (HSF) is a compound Chinese herbal medicine prescription, and has long been used for treating chronic non-healing wounds. Aim of the studyThe purpose of this study was to provide new insight into molecular mechanisms of healing effects of the HSF treatments. Materials and methodsWe established a rat diabetic skin ulcer (DSU) model, and assessed healing effects of four HSF treatments on DSUs by calculating wound healing rates and immunohistochemical detection of the expressions of angiogenesis-related factors in the model rats (Mod) relative to normal rats (Nor), including Huiyang extract (HE), Shengji extract (SE), Huiyang Shengji extract (HSE) and HSE associated with acupuncture (Ac-HSE). We then performed NMR-based metabolomic analyses on skin tissues of the Nor, Mod, HSE-treated, Ac-HSE-treated rats to address metabolic mechanisms underlying these effects. ResultsThese treatments up-regulated expressions of two angiogenesis-related factors VEGF and CD31, and improved efficacy of healing DSUs, in which HSE and Ac-HSE exhibited the most significant effects. Compared with Mod, HSE and Ac-HSE groups shared four characteristic metabolites (lactate, histidine, succinate and acetate) and four significantly altered metabolic pathways with Nor. Both HSE and Ac-HSE treatments could partly reverse the metabolically disordered pathological state of DSUs to the normal state. They might improve wound healing through promoting glucose metabolism, BCAAs metabolism, and enhancing antioxidant capacity and angiogenesis in DSU tissues. Ac-HSE significantly enhanced wound healing rates compared to HSE, potentially owing to significant capacities of enhancing anti-oxidation and angiogenesis and interfering three more metabolic pathways. ConclusionsThis work provides a mechanistic understanding of the healing effects of the HSE and Ac-HSE treatments on DSUs, is of benefit to improvements of the HSF treatments for clinically healing chronic non-healing wounds.

Efficacy of compound Bai Yu San in treating diabetic skin ulcer

Objective: To assess the efficacy of compound Bai Yu San (CBYS) as a new treatment option, in healing diabetic skin ulcer. Materials and Methods: A total of 64 diabetic patients with skin ulcer were enrolled and randomly assigned to experimental group (n = 33) and control group (n = 31). In the control group, normal saline (NS) was used to cleanse the wound. After debridement, the wound was dressed with modern materials. In the experimental group, the NS-cleansed wound was dressed with CBYS. The infection rate, healing rate, treatment cost, and patient satisfaction between the two groups were compared. Results: On the 35th day after treatment, the infection rate and healing rate showed no between-group difference (P > 0.05); the experimental group showed lower treatment cost and higher satisfaction than the control group (P Conclusion: As a new treatment option for diabetes-induced skin ulcer, CBYS can effectively control the infection, promote the healing, reduce treatment cost, and increase patient satisfaction. Dressing with CBYS can be clinically replicated in the treatment of diabetic skin ulcer.

Effect of supernatant of mesenchymal stem cells on tumor necrosis factor-α and apoptosis protein caspase-3 in diabetic skin ulcer rat model

Objective To investigate the supernatant of umbilical cord-derived mesenchymal stem cells (UCMSCs) on tumor necrosis factor-α (TNF-α) and apoptosis protein caspase-3 in diabetic rats model with skin ulcer. Methods 45 Sprague-Dawley rats were randomly divided into control group (acute wounds group), phosphate buffered saline (PBS) group and UCMSCs supernatant group. The diabetic rat model was constructed by injecting with alloxan by tail vein and feeding with high-fat diet. Diabetic skin ulcer (DSU) rat model was constructed by scratching a wound and infusing suspension of Staphylococcus aureus. In the control group, the diabetic rats (n=15) were scratched to form a wound and treated by tail vein injection of 100 μl PBS. In the PBS group, DSU rats (n=15) were treated by tail vein injection of 100 μl PBS, and then 100 μl PBS was dropped at the ulcer site. In the UCMSCs supernatant group, freeze-dried powder of UCMSCs supernatant was dissolved in 200 μl PBS, 100 μl of which was injected into the tail vein of DSU rats (n=15), and other 100 μl was dropped at the ulcer site. After 5 days of the treatments, the levels of serum TNF-α were detected by radioimmunoassay method, and the expression of TNF-α and caspase-3 in the ulcer tissues of rats was detected by polymerase chain reaction and Western Blot. Results The levels of TNF-α in the PBS group [(35.9±3.7) μg/L] were significantly higher than that of the control group [(11.4±4.9) μg/L] and the UCMSCs group [(14.7±6.6) μg/L] (all P 0.05). Conclusions UCMSCs supernatant treatments can effectively down-regulate the expression of TNF-α and caspase-3 in ulcer tissue of DSU rats, and play an anti-inflammatory and anti-apoptotic effect. Key words: Diabetes mellitus; Skin ulcer; Umbilical cord derived-mesenchymal stem cells; Tumor necrosis factor-α; Caspase-3

Bi-layer supramolecular polydimethylsiloxane elastomer film: Synthesis, characterization, and application in wound dressing on normal and diabetic rat

Treatment of chronic wounds, such as diabetic feet, pressure sores and skin ulcer, has been a difficult issue for wound dressings. It is of great interest but challenging to develop an ideal dressing for chronic wounds with long-term functionality, transparency for clinical observation and adaptability to skin deformation. In this work, we designed a supramolecular polydimethylsiloxane (PDMS) elastomer material with double layer structure. After a series characterizations including mechanical properties, adhesion properties, water-vapor permeability and bio-compatibility, this bi-layer film (BLF) is evaluated as a wound dressing in the wound healing model in both normal and diabetic rat. The results show that the BLF dressing has good bio-compatibility, similar moisture permeability and adhesion properties compared with a commercial medical Tegaderm™ film. Moreover, benefiting from the comparatively lower modulus, the BLF dressing provides more stable attachment to the skin and an enclosed moist healing environment for the wounds, which is found to promote the healing process in the early stage.

Resveratrol Promotes Diabetic Wound Healing via SIRT1-FOXO1-c-Myc Signaling Pathway-Mediated Angiogenesis.

Background/Aims: Diabetic non-healing skin ulcers represent a serious challenge in clinical practice, in which the hyperglycemia-induced disturbance of angiogenesis, and endothelial dysfunction play a crucial role. Resveratrol (RES), a silent information regulator 1 (SIRT1) agonist, can improve endothelial function and has strong pro-angiogenic properties, and has thus become a research focus for the treatment of diabetic non-healing skin ulcers; however, the underlying mechanism by which RES regulates these processes remains unclear. Therefore, the present study was intended to determine if RES exerts its observed protective role in diabetic wound healing by alleviating hyperglycemia-induced endothelial dysfunction and the disturbance of angiogenesis.Methods: We investigated the effects of RES on cell migration, cell proliferation, apoptosis, tube formation, and the underlying molecular mechanisms in 33 mM high glucose-stimulated human umbilical vein endothelial cells (HUVECs) by semi-quantitative RT-PCR, western blot analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and immunofluorescence in vitro. We further explored the role of RES on endothelial dysfunction and wound healing disturbance in db/db mice by TUNEL staining, immunofluorescence, and photography in vivo.Results: We observed an obvious inhibition of hyperglycemia-triggered endothelial dysfunction and a disturbance of angiogenesis, followed by the promotion of diabetic wound healing via RES, along with restoration of the activity of the hyperglycemia-impaired SIRT1 signaling pathway. Pretreatment with EX-527, a SIRT1 inhibitor, abolished the RES-mediated endothelial protection and pro-angiogenesis action, and then delayed diabetic wound healing. Furthermore, examination of the overexpression of forkhead box O1 (FOXO1), a transcription factor substrate of SIRT1, in HUVECs and db/db mice revealed that RES activated SIRT1 to restore hyperglycemia-triggered endothelial dysfunction and disturbance of angiogenesis, followed by the promotion of diabetic wound healing in a c-Myc-dependent manner. Pretreatment with 10058-F4, a c-Myc inhibitor, repressed RES-mediated endothelial protection, angiogenesis, and diabetic wound healing.Conclusion: Our findings indicate that the positive role of RES in diabetic wound healing via its SIRT1-dependent endothelial protection and pro-angiogenic effects involves the inhibition of FOXO1 and the de-repression of c-Myc expression.

Protection of glucotoxicity by a tripeptide derivative of α-melanocyte-stimulating hormone in human epidermal keratinocytes.

Chronic skin ulcers are a major complication and a therapeutic challenge in patients with diabetes mellitus. Glucose-induced accumulation of reactive oxygen species (ROS) is considered to be an important pathogenetic factor in diabetes. To characterize the impact of high glucose (HG) on normal human keratinocytes (NHKs) and examine if Lys-d-Pro-Thr (KdPT), a tripeptide derived from α-melanocyte-stimulating-hormone, has protective effects. We investigated the key functions of NHKs under HG conditions with or without KdPT in vitro as well as ex vivo employing a skin organ culture model. HG impaired metabolic activity, cell proliferation, viability and migration of NHKs. As shown by atomic force microscopy HG altered the biophysical properties of NHKs, i.e. cell size and elasticity. Glucotoxicity in NHKs was paralleled by the induction of intracellular ROS and endoplasmic reticulum stress. KdPT attenuated HG-induced oxidative stress and antagonized the effects of glucose on cell viability, metabolic activity and migration. Importantly, KdPT also antagonized the suppressive effect of HG on epidermal migration in wounded human skin organ cultures. Our findings highlight a novel effect of KdPT that could be exploited for the future therapy of diabetic skin ulcers.

Topical Application of Culture-Expanded CD34+ Umbilical Cord Blood Cells from Frozen Units Accelerates Healing of Diabetic Skin Wounds in Mice.

Chronic and nonhealing wounds are constant health issues facing patients with type 2 diabetes. As the incidence of type 2 diabetes mellitus (T2DM) increases, the incidence of chronic wounds and amputations will rise. T2DM is associated with peripheral arterial occlusive disease, which leads to the development of nonhealing skin ulcers after minor trauma. Patients develop severe pain limiting their mobility and ability to work and take care of themselves, thus putting a significant burden on the family and society. CD34+ cells from umbilical cord blood (UCB) grown in fibroblast growth factor‐4 (FGF‐4), stem cell factor, and Flt3‐ligand produced a population of cells that have the ability to proliferate and develop properties enabling them to enhance tissue regeneration. The goal of this study was to assess in vitro cultured CD34+ cells in a setting where they would eventually be rejected so we could isolate paracrine signaling mediated therapeutic effect from the therapeutic effect due to engraftment and differentiation. To achieve this, we used db/db mice as a model for diabetic skin ulcers. Here, we report that in vitro cultured UCB CD34+ cells from frozen units can accelerate wound healing and resulted in the regeneration of full thickness skin. This study demonstrates a new indication for banked UCB units in the area of tissue regeneration. Stem Cells Translational Medicine 2018;7:591–601

Palmitic acid dysregulates the Hippo–YAP pathway and inhibits angiogenesis by inducing mitochondrial damage and activating the cytosolic DNA sensor cGAS–STING–IRF3 signaling mechanism

Impaired angiogenesis and wound healing carry significant morbidity and mortality in diabetic patients. Metabolic stress from hyperglycemia and elevated free fatty acids have been shown to inhibit endothelial angiogenesis. However, the underlying mechanisms remain poorly understood. In this study, we show that dysregulation of the Hippo-Yes-associated protein (YAP) pathway, an important signaling mechanism in regulating tissue repair and regeneration, underlies palmitic acid (PA)-induced inhibition of endothelial angiogenesis. PA inhibited endothelial cell proliferation, migration, and tube formation, which were associated with increased expression of mammalian Ste20-like kinases 1 (MST1), YAP phosphorylation/inactivation, and nuclear exclusion. Overexpression of YAP or knockdown of MST1 prevented PA-induced inhibition of angiogenesis. When searching upstream signaling mechanisms, we found that PA dysregulated the Hippo-YAP pathway by inducing mitochondrial damage. PA treatment induced mitochondrial DNA (mtDNA) release to cytosol, and activated cytosolic DNA sensor cGAS-STING-IRF3 signaling. Activated IRF3 bound to the MST1 gene promoter and induced MST1 expression, leading to MST1 up-regulation, YAP inactivation, and angiogenesis inhibition. Thus, mitochondrial damage and cytosolic DNA sensor cGAS-STING-IRF3 signaling are critically involved in PA-induced Hippo-YAP dysregulation and angiogenesis suppression. This mechanism may have implication in impairment of angiogenesis and wound healing in diabetes.

Skin Regeneration with Self-Assembled Peptide Hydrogels Conjugated with Substance P in a Diabetic Rat Model

The wound healing process requires enough blood to supply nutrients and various growth factors to the wound area. However, chronic wounds such as diabetic skin ulcers have limited regeneration due to a lack of cellular and molecular signals because of a deficient blood flow. Mesenchymal stem cells (MSCs) are known to provide various factors, including growth factors, cytokines, and angiogenic mediators. Although MSCs have great therapeutic potential, their transplantation has many obstacles, including the time required to culture the cells, the invasiveness of the procedure, and limited stem cell sources. In this study, we induced a diabetic 1 model in rats aged 7 weeks by injecting streptozotocin and citrate buffer solution. After confirming that diabetes was induced in the rats, we created critical sized wounds on the dorsal area of the rats and then injected hydrogels. We performed the experiments with four groups (defect model for the control, self-assembled peptides (SAPs), SAP with soluble substance P, and SAP conjugated with substance P) to treat the wound defect. Tissues were harvested at 1, 2, and 3 weeks after injection and examined for the wound closure, histological analysis, quantitative real-time polymerase chain reaction analysis, and quantification of collagen deposits to investigate stem cell recruitment and full recovery of wounds at an accelerated time period. As our results show, the wounds treated with SAP and substance P exhibited significantly accelerated wound closure, enhanced collagen deposition, and increased angiogenesis. Furthermore, we confirmed the ability of SAP with substance P to promote the recruitment and homing of cells by immunofluorescence staining of a MSC marker. In addition, it was observed that substance P remained in the wound area up to 3 weeks after the injection of SAP with substance P. It is believed that the endogenous MSCs mobilized by substance P had therapeutic effects through their proper differentiation and release of paracrine factors into the wound sites. In conclusion, this study shows that SAP with substance P can promote wound healing to enhance skin regeneration without cell transplantation in a diabetic model.

The Unraveling Truth About IRE1 and MicroRNAs in Diabetes.

Wound healing is a well-regulated complex process that occurs as a cellular response to injury and consists of four phases: hemostasis, inflammation, proliferation, and remodeling (1). Many factors, such as diabetes and obesity, interfere with these stages and lead to wound healing defect. Diabetes affects approximately 170 million people worldwide, including 20.8 million in the U.S., and by 2030 these numbers are projected to double (2). Impaired wound healing is a major clinical problem in patients with diabetes and is the leading cause of lower-extremity amputation and comorbidity associated with diabetes. Diabetic skin ulcers are estimated to occur in 15% of all patients with diabetes and 84% of all diabetes-related lower-leg amputations (3,4). Despite current treatments, one in four patients with diabetic ulcers will have a foot amputation. Therefore, new treatment strategies for healing diabetic skin ulcers are highly needed. Impaired or delayed wound healing in diabetes is characterized by impaired angiogenesis and vasculogenesis (5). Adult bone marrow progenitor cells, bone marrow–derived endothelial progenitor cells (BMPCs), can home to injured tissue and participate in the tissue repair regeneration process. However, in diabetes, BMPCs are dysfunctional (defective recruitment and reduced survival and proliferation) (6). The mechanism of bone marrow cell dysfunction in diabetes is not yet fully understood. Endoplasmic reticulum (ER), a multifunctional organelle involved in …

Fabrication of Waterproof, Breathable Composite Liquid Dressing and Its Application in Diabetic Skin Ulcer Repair.

Diabetic patients are at increased risk of severe skin infections. Covering the wound as early as possible can prevent infection and shorten the course of treatment. In this study, the authors fabricated a waterproof and breathable composite liquid dressing (CLD) that formed a barrier to bacteria and shortened healing time of diabetic rat skin ulcers. The CLD was prepared in a formulation that, on evaporation of the liquid carrier, acts as a waterproof, breathable coating on injured skin. The coating was analyzed for water resistance, moisture vapor transmission rate (MVTR), bacterial barrier properties, sustained-release function, and biosafety. A chemically induced rat model of diabetic foot ulcers was used to examine the wound healing effect of CLD and CLD that contained Dermlin (Yensen Biotech Co, Jiangyin, Jiangsu, China). The wound healing rate, histologic changes, and epidermal growth factor expression were also evaluated. The CLD functioned as an effective barrier against infection, was waterproof, had a suitable MVTR, and had effective biosafety. The synergistic effects of CLD and Dermlin had a rapid wound closure rate. Histologic analysis and measurement of epidermal growth factor expression through an in vivo test revealed that the possible mechanism of the CLD effects included the reduction of inflammation and promotion of cell proliferation. Early treatment with the CLD can prevent infection. In combination with Dermlin, the CLD may promote better wound closure in diabetic skin ulcers. The authors' study suggests a novel strategy for ulcer healing.