Development Of Chronic Wounds Research Articles

Chronıc Wound Formatıon on an Old Burn Scar after Surgıcal Incısıon and Hyperbarıc Oxygen Therapy: Case Report

A burn scar may have varying degrees of functional and aesthetic components. However chronic wound formation after surgical incision on old burn scar hasn't been reported. In this report, we present hyperbaric oxygen (HBO) therapy application in a case who had a chronic wound development on an old burn scar after performing a 3 cm incision on pubis during the surgery of transurethral resection of the prostate (TUR-P) because of urethral stricture.

Biopelículas bacterianas en heridas crónicas

En las últimas tres décadas, el estudio de las biopelículas bacterianas ha tomado gran relevancia gracias a su identificación como uno de los factores más importantes en el desarrollo de infecciones crónicas. Una de las patologías de mayor interés en el área de la salud, y de la cual se ha logrado profundizar en mayor medida, corresponde a las heridas crónicas, en donde se estima que las biopelículas bacterianas están presentes en el 60%, comparadas con las heridas agudas en donde se presentan solo en el 20%.
 Las heridas crónicas representan el 1-2% de todas las heridas a nivel mundial, pero la carga socioeconómica y emocional que generan, repercute notablemente debido a los costos en curaciones, tratamientos convencionales y en complicaciones tan graves como las amputaciones de extremidades. El objetivo de este artículo de revisión es proporcionar información relevante sobre el concepto de las biopelículas bacterianas, su implicación en el desarrollo de heridas crónicas, el diagnóstico y los posibles tratamientos.

Rapid treatment of full‐thickness skin loss using ovine tendon collagen typeIscaffold with skin cells

The full-thickness skin wound is a common skin complication affecting millions of people worldwide. Delayed treatment of this condition causes the loss of skin function and integrity that could lead to the development of chronic wounds or even death. This study was aimed to develop a rapid wound treatment modality using ovine tendon collagen type I (OTC-I) bio-scaffold with or without noncultured skin cells. Genipin (GNP) and carbodiimide (EDC) were used to cross-link OTC-I scaffold to improve the mechanical strength of the bio-scaffold. The physicochemical, biomechanical, biodegradation, biocompatibility, and immunogenicity properties of OTC-I scaffolds were investigated. The efficacy of this treatment approach was evaluated in an in vivo skin wound model. The results demonstrated that GNP cross-linked OTC-I scaffold (OTC-I_GNP) had better physicochemical and mechanical properties compared with EDC cross-linked OTC-I scaffold (OTC-I_EDC) and noncross-link OTC-I scaffold (OTC-I_NC). OTC-I_GNP and OTC-I_NC demonstrated no toxic effect on cells as it promoted higher cell attachment and proliferation of both primary human epidermal keratinocytes and human dermal fibroblasts compared with OTC-I_EDC. Both OTC-I_GNP and OTC-I_NC exhibited spontaneous formation of bilayer structure in vitro. Immunogenic evaluation of OTC-I scaffolds, in vitro and in vivo, revealed no sign of immune response. Finally, implantation of OTC-I_NC and OTC-I_GNP scaffolds with noncultured skin cells demonstrated enhanced healing with superior skin maturity and microstructure features, resembling native skin in contrast to other treatment (without noncultured skin cells) and control group. The findings of this study, therefore, suggested that both OTC-I scaffolds with noncultured skin cells could be promising for the rapid treatment of full-thickness skin wound.

Histological and morphometric assessment of cutaneous wound healing in streptozotocin-induced diabetic rats treated with n-hexane extract of Leptadenia hastata

CONTEXT: A wound is defined as a loss or breaking of cellular, anatomical, or functional continuity of living tissues. Diabetes may delay the process of wound healing leading to development of chronic wounds. Healing impairment of diabetic wounds presents serious clinical problems for both diabetic patients and physicians worldwide. AIMS: This study aims to validate the use of Leptadenia hastata in the treatment of diabetic and nondiabetic wounds. SETTINGS AND DESIGN: Diabetes mellitus was induced in twenty Albino rats using a single injection of streptozotocin (50 mg/kg i.p.). The rats were divided into four groups (III–VI) consisting of five rats each. In addition, ten nondiabetic rats were grouped into I and II. SUBJECTS AND METHODS: Full-thickness excision wounds extending to the subcutaneous tissue were made on the mid-dorsal region, and rats in Group III–VI had their wounds treated with olive oil, 100 mg/kg of extract, 200 mg/kg of extract, and procaine penicillin, respectively. Rats in Groups I and II received olive oil and 200 mg/kg of extract, respectively, for 28 days. Wound areas were calculated, and histological sections of the wound area were analyzed. STATISTICAL ANALYSIS USED: Data were statistically analyzed using GraphPad InStat software using one-way analysis of variance and expressed as mean ± standard error of mean and percentage followed by Bonferroni multiple comparisons test. RESULTS: Analysis of wound area in all groups revealed that the extract promoted wound healing in the diabetic rats by significantly (P CONCLUSIONS: The extract enhanced diabetic wound healing by reducing inflammation, increasing wound contraction and epithelialization.

A pH-sensitive near-infrared fluorescent probe with alkaline pKa for chronic wound monitoring in diabetic mice.

A pH-sensitive near-infrared fluorescent probe with alkaline pKa, AlkaP-1, was developed by incorporating a benzoyl hydrazine group into a cyanine dye. The significant fluorescence changes in the alkaline regions enable the probe to monitor the alkalization process from acute wounds to chronic wounds in diabetic mice.

Cotton‐hydrogel composite for improved wound healing: Antimicrobial activity and anti‐inflammatory evaluation—Part 2

Infection is one of the major risk factors for the development of chronic wounds. Antimicrobial wound dressing has been pointed out as a viable option for the prevention and treatment of wound infections. Thus, we developed a composite material based on cotton textile substrates functionalized with cyclodextrin‐hydroxypropyl methyl cellulose‐based hydrogel. The composites' ability to encapsulate and release gallic acid (antimicrobial phenolic acid) was evaluated, as well as their mechanical properties and antimicrobial and anti‐inflammatory capacity. All composites were able to retain gallic acid in their structure, with similar loading profile. The presence of gallic acid on composites was confirmed by FTIR and TGA. Composites storage moduli was reduced by the presence of gallic acid. The results suggest a straight relation between the swelling ability and gallic acid drug delivery profile. The drug delivery mechanism, of the developed composites, was mainly controlled by Fickian diffusion, based on the experimental data fitting to the Peppas‐Sahlin model. Gallic acid antimicrobial and anti‐inflammatory properties were transferred to the composite materials. According to the results, the developed composites can be applied on the prevention or treatment of chronic wounds.

New insights into the roles of myofibroblasts and innervation during skin healing and innovative therapies to improve scar innervation.

During the resolution phase of normal skin wound healing, there is a considerable loss of various cell types, including myofibroblasts by apoptosis. Inappropriate delay of apoptosis, and thus increased survival of myofibroblasts, may be a factor leading to pathologies and excessive scarring. Considerable data now clearly suggest that innervation plays a major role in wound healing, including the modulation of fibroblast cellular activity. An abnormal level of neuromediators is implicated not only in the development of chronic wounds but also in excessive scar formation. Understanding interactions between neuromediators and myofibroblasts, allowing normal reinnervation and having adequate levels of neuromediators during the healing process are clearly important to avoid the appearance of pathological healing or fibrosis/scarring. The aim of this review was first to discuss the mechanisms leading to normal or excessive scarring and then to present the roles of innervation during wound healing. Finally, the latest therapeutic strategies to help wound repair and reinnervation after skin damage will be introduced. Advantages and limitations in the use of neuropeptides, growth factors and biomaterials will be discussed as well as the most recent studies on electrostimulation and the potential of targeting resident skin mesenchymal stem cells.

Elevated Thrombospondin‐2 Contributes to Delayed Wound Healing in Diabetes

Impaired wound healing is a major complication of diabetes and can lead to the development of chronic wounds in a significant portion of diabetes patients. Despite the risks posed by impaired healing, treatment strategies for diabetic wounds remain limited due to an incomplete understanding of the underlying pathological mechanisms. Previous studies have demonstrated that overexpression of thrombospondin‐2 (TSP2), a matricellular protein released after tissue injury, is associated with significant delays in dermal healing in various mouse models. Consistently, wounds lacking TSP2 (TSP2 KO) heal faster than wounds in wild‐type mice or mice with elevated TSP2. Thus, the present study aimed to examine the role of TSP2 in delayed healing in diabetes.First, we evaluated TSP2 expression in human wounds, and found that TSP2 is elevated in wounds from diabetes patients. Then, to determine TSP2's contribution to impaired healing in diabetes, we developed a novel diabetic TSP2 KO mouse model. Though these db/db TSP2 KO mice develop obesity and hyperglycemia comparable to db/db mice, db/db TSP2 KO mice exhibit significantly improved healing. Moreover, primary fibroblasts isolated from db/db TSP2 KO mice exhibit improved migration, providing mechanistic insight into the accelerated healing in these mice. We also studied TSP2 expression in fibroblasts, the major source of TSP2 in the wound, to explore the mechanisms leading to its overexpression in diabetes. Our results showed that TSP2 expression is increased in hyperglycemia, through increased activation of the hexosamine biosynthesis pathway and subsequent O‐GlcNAc modification of transcriptional elements. Overall, the results of this study indicate for the first time that: 1) TSP2 expression is elevated in diabetes and hyperglycemia and 2) TSP2 contributes to impaired healing in diabetes. These results represent a novel role for TSP2 in diabetes complications and a novel target for improving wound healing in diabetes.Support or Funding InformationNIH HL107205, NIH GM 072194, Gruber Science FellowshipThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Clinical management of non-healing wounds

Chronic wounds are defined as those that have failed to heal after three months. There are various intrinsic and extrinsic factors that may result in the development of chronic wounds, including comorbidities such as diabetes mellitus and venous insufficiency, and lifestyle factors such as obesity, alcohol consumption and smoking. Chronic wounds represent a significant burden on healthcare resources and can have a negative effect on patients' quality of life. This article discusses the assessment and treatment of non-healing chronic wounds. It examines the normal wound-healing process and the management of chronic wounds, including advanced interventions such as electrical stimulation therapy, negative pressure wound therapy and various dressings. This article does not focus on specific wound types; instead, it provides an overview of the factors that can lead to the development of chronic wounds and how these wounds can be managed in clinical practice.

The development of a 'wet leg' pathway for chronic oedema.

Chronic oedema and leaking lymphorrhoea can be distressing and challenging for patients to live with. This article introduces the Chronic Oedema 'Wet Leg' Pathway, which became an output from the Lymphoedema Network Wales 'On the Ground Education Project' ( Thomas et al, 2017 ). The evidence-based pathway provides nurses and therapists with clear guidelines to support prompt, efficient and effective management of all patients with chronic oedema and wet legs. This article presents the evidence and demonstrates the benefits of timely active treatment for all patients with leaking lymphorrhoea, which includes decreasing pain and improving mobility and daily activities. Other benefits include reducing the risk of cellulitis and the development of chronic wounds. The pathway also demonstrates opportunities for the NHS by decreasing both the number of community nursing visits and the number of wound dressings used. By actively treating symptoms-rather than simply mopping up the leaking lymphorrhoea-this pathway demonstrates value-based health care by reducing waste, harm and variation within the NHS.

Impact of repeated abdominal surgery on wound healing and myeloid cell dynamics

BackgroundEven though wound dehiscence is a surgical complication, under certain medical conditions, repetition of the laparotomy (LT) (relaparotomy) can become inevitable. In addition to the risks associated with this surgical operation, relaparotomy can interfere with the tissue healing and contribute to the development of chronic wounds. MethodsIn an experimental relaparotomy wounding model, this study investigated the impact of repeated surgery on wound healing and on the immune cells of myeloid origin. ResultsThe first repeat of the LT triggered fibrosis and marginally interfered with the wound healing; however, the second operation completely abrogated the healing process. Splenomegaly was observed as an indicator of the chronic inflammation and the systemic effect of repeated laparotomies. In the blood stream, the spleen, and the liver, these repeated surgeries exhibited a major impact on the CD11b+Ly6C+Ly6G− monocytes. On the other hand, especially, whespecially the second relaparotomy resulted in a massive purging of neutrophil granulocytes into the circulation. These CD11b+Ly6C+Ly6G+ neutrophils that were disseminated on repeated abdominal laparotomies had a proinflammatory character that positively influenced T cell proliferation and displayed a high capacity for production of reactive oxygen species. ConclusionsThe repetition of abdominal LT not only interferes with the wound healing but also contributes to the development of imperfectly healing wounds which have systemic impact on immune compartments.

Skin tears and risk factors assessment: a systematic review on evidence-based medicine.

Skin tears represent a common condition of traumatic wounds, which may be encountered in some categories of individuals at the extremes of age, such as infants and the elderly. Despite the high prevalence and cost of these lesions, there has been little investigation into the risk factors that lead to this condition. The aim of this review was to systematically evaluate the main risk factors involved in development of skin tears. We planned to include all the studies dealing with risk factors related to skin tears. Only publications in English were considered. We excluded all the studies that did not properly fit our research question and those with insufficient data. Of the 166 records found, 24 matched our inclusion criteria. After reading the full-text articles, we decided to exclude seven articles because of the following reasons: (1) not responding properly to our research questions and (2) insufficient data; the final set included 17 articles. From a literature search, we found the following main issues related to risk factors, which have been described in detail in this section: age-related skin changes, dehydration, malnutrition, sensory changes, mobility impairment, pharmacological therapies and mechanical factors related to skin care practices. Our findings clearly show that in frail populations (especially infant and elderly), the stratification risk, as a primary prevention strategy, is an effective tool in avoiding the development of chronic wounds. The development and the implementation of prevention strategies based on appropriate knowledge of the risk factors involved and the adoption of correct techniques during skin care practices could reduce or even avoid the onset of skin tears.

Novel Locally Active Estrogens Accelerate Cutaneous Wound Healing-Part 2

Estrogen deprivation is associated with delayed healing, while estrogen replacement therapy (ERT) accelerates acute wound healing and protects against development of chronic wounds. However, current estrogenic molecules have undesired systemic effects, thus the aim of our studies is to generate new molecules for topic administration that are devoid of systemic effects. Following a preliminary study, the new 17β-estradiol derivatives 1 were synthesized. The estrogenic activity of these novel compounds was evaluated in vitro using the cell line ERE-Luc B17 stably transfected with an ERE-Luc reporter. Among the 17β-estradiol derivatives synthesized, compounds 1e and 1f showed the highest transactivation potency and were therefore selected for the study of their systemic estrogenic activity. The study of these compounds in the ERE-Luc mouse model demonstrated that both compounds lack systemic effects when administered in the wound area. Furthermore, wound-healing experiments showed that 1e displays a significant regenerative and anti-inflammatory activity. It is therefore confirmed that this class of compounds are suitable for topical administration and have a clear beneficial effect on wound healing.

Angelica Dahurica ethanolic extract improves impaired wound healing by activating angiogenesis in diabetes.

Abnormal angiogenesis plays an important role in impaired wound healing and development of chronic wounds in diabetes mellitus. Angelica dahurica radix is a common traditional Chinese medicine with wide spectrum medicinal effects. In this study, we analyzed the potential roles of Angelica dahurica ethanolic extract (ADEE) in correcting impaired angiogenesis and delayed wound healing in diabetes by using streptozotocin-induced diabetic rats. ADEE treatment accelerated diabetic wound healing through inducing angiogenesis and granulation tissue formation. The angiogenic property of ADEE was subsequently verified ex vivo using aortic ring assays. Furthermore, we investigated the in vitro angiogenic activity of ADEE and its underlying mechanisms using human umbilical vein endothelial cells. ADEE treatment induced HUVECs proliferation, migration, and tube formation, which are typical phenomena of angiogenesis, in dose-dependent manners. These effects were associated with activation of angiogenic signal modulators, including extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, endothelial nitric oxide synthase (eNOS) as well as increased NO production, and independent of affecting VEGF expression. ADEE-induced angiogenic events were inhibited by the MEK inhibitor PD98059, the PI3K inhibitor Wortmannin, and the eNOS inhibitor L-NAME. Our findings highlight an angiogenic role of ADEE and its ability to protect against impaired wound healing, which may be developed as a promising therapy for impaired angiogenesis and delayed wound healing in diabetes.

Physical medicine modalities most frequently applied in the lower limbs chronic wounds treatment in Poland

Abstract Introduction Chronic wounds are the ones that present no healing progress for more than three months. The most common reasons for the chronic wound development in the lower limbs include long-lasting diabetes mellitus, venous insufficiency and peripheral arterial disease. However, it is estimated that 15%–20% of the lower limb chronic wounds are of mixed etiology. Standard treatments such as pharmacotherapy, debridement or skin grafting may be supplemented with physical medicine modalities. Aim The aim of the paper was to indicate the utility and biological effects of the physical medicine modalities frequently applied in chronic wound treatment. Discussion The physical medicine modalities widely used in the lower limbs chronic wounds treatment are variable magnetic fields, low-level laser therapy and hyperbaric oxygen therapy. Those modalities are proved to stimulate various biological reactions which may promote chronic wound healing. Stimulation of angiogenesis and collagen proliferation are factors that promote histological wound maturation and closure. Local circulation improvement mediated by hypocoagulation and vasodilatation is a factor accelerating wounds healing. Modalities-mediated pain reduction is a result of anti-inflammatory activity as well as of endogenous endorphin secretion. Modalities-mediated bacteriostatic and bactericidal effects are also observed. All those effects are mediated by activation of the immune system. An anti-inflammatory effect is due to the inhibition of pro-inflammatory cytokines secretion and the increase in interleukins activity. Conclusions Variable magnetic fields, low-level laser therapy and hyperbaric oxygen therapy are modalities revealing various working mechanisms. The significance of their administration in chronic wounds treatment can be attributed to a variety of their biological effects.

Effects of Ankaferd BloodStopper on dermal healing in diabetic rats.

Diabetes mellitus inhibits wound-induced angiogenesis, impairs the wound healing process, and leads to the development of chronic wounds. Ankaferd BloodStopper (ABS) is a new and promising local haemostatic agent. Although the mechanism of ABS-mediated haemostasis is well established, little is known about the associated histological and biochemical tissue reactions. The aim of this study was to evaluate the effects of this new-generation local haemostatic agent on short-term soft-tissue healing in streptozotocin (STZ)-treated rats. The 24 Wistar albino rats used in this study were divided into STZ-treated (STZ, n = 12) and nontreated groups (control, n = 12). Four days prior to surgery, rats in the STZ group were subcutaneously administered 60 mg/kg STZ intraperitoneally, while rats in the control group were administered 1 mL saline/kg. An incision was made in the dorsal dermal tissue of all rats, and either ABS or no haemostatic agent (NHAA) was applied to the wound before suturing. All of the rats were euthanised on postoperative day 4. Blood and skin samples were evaluated biochemically and histologically. The results showed that STZ treatment impaired soft-tissue healing, assessed by measuring glutathione and lipid peroxidation levels. Moreover, while good histological results were obtained in the control group treated with ABS, there were fewer benefits in the STZ-treated group. ABS's benefits in the control group seemed to lose their effectiveness under STZ medication.

Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP activity

Many chronic wounds exhibit high matrix metalloproteinase (MMP) activity that impedes the normal wound healing process. Intradermal delivery (IDD) of sub-antimicrobial concentrations of doxycycline, as an MMP inhibitor, could target early stages of chronic wound development and inhibit further wound progression. To deliver doxycycline intradermally, the skin barrier must be disrupted. Microneedle rollers offer a minimally invasive technique to penetrate the skin by creating multiple microchannels that act as temporary conduits for drugs to diffuse through. In this study, an innovative and facile approach for delivery of doxycycline across Strat-MTM membrane was investigated using microneedle rollers. The quantity and rate of doxycycline diffusing through the micropores directly correlated with increasing microneedle lengths (250, 500 and 750 μm). Treatment of Strat-MTM with microneedle rollers resulted in a reduction in fibroblast-mediated collagen gel contraction and MMP activity compared with untreated Strat-MTM. Our results show that treatment of an epidermal mimetic with microneedle rollers provides sufficient permeabilization for doxycycline diffusion and inhibition of MMP activity. We conclude that microneedle rollers are a promising, clinically ready tool suitable for delivery of doxycycline intradermally to treat chronic wounds.

PH-Modulating Poly(ethylene glycol)/Alginate Hydrogel Dressings for the Treatment of Chronic Wounds.

The development of chronic wounds has been frequently associated with alkaline pH values. The application of pH-modulating wound dressings can, therefore, be a promising treatment option to promote normal wound healing. This study reports on the development and characterization of acidic hydrogel dressings based on interpenetrating poly(ethylene glycol) diacrylate/acrylic acid/alginate networks. The incorporation of ionizable carboxylic acid groups results in high liquid uptake up to 500%. The combination of two separate polymer networks significantly improves the tensile and compressive stability. In a 2D cell migration assay, the application of hydrogels (0% to 1.5% acrylic acid) results in complete "wound" closure; hydrogels with 0.25% acrylic acid significantly increase the cell migration velocity to 19.8 ± 1.9 µm h-1 . The most promising formulation (hydrogels with 0.25% acrylic acid) is tested on 3D human skin constructs, increasing keratinocyte ingrowth into the wound by 164%.

Synthesis and characterization of silver nanoparticle incorporated gelatin‐hydroxypropyl methacrylate hydrogels for wound dressing applications

ABSTRACTA replaceable wound cover which absorbs moisture and resist infection can be used to prevent development of chronic wounds. A major criterion for a replaceable wound dressing is nonadherence to cells to prevent pain upon removal. A major limitation of water absorbing hydrogels used in wound dressing applications is their poor mechanical strength. In this study, gelatin methacrylate (GelMA) was synthesized by reacting Type A porcine skin gelatin with methacrylic anhydride at 50 °C. Resultant GelMA monomer containing polyethylene glycol (PEG) protected silver nanoparticles were subsequently copolymerized with 2‐hydroxypropyl methacrylate (HPMA) at room temperature by redox mechanism. This resulted in a hydrogel copolymer with optimum mechanical stability and moisture retention while inhibiting microbial contamination and FT‐IR spectroscopy was used to confirm copolymer formation. Antimicrobial properties of the hydrogel using agar diffusion showed zone of inhibition against Staphylococcus aureus. Surface morphology was observed using scanning electron microscopy (SEM) and elemental analysis was carried out using energy‐dispersive spectroscopy (EDS). Micro‐computed tomography (micro‐CT) analysis of the hydrogel showed enhancement in the pore size from around 32 µ to 48–64 µ after incorporation of silver nanoparticles. Degradation of the hydrogel was observed after 48 h when stored in PBS containing collagenase enzyme. In vitro cell culture experiments established absence of cytotoxicity in the hydrogel and nonadherence character to dermal fibroblasts. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44529.

Reactive oxygen species and bacterial biofilms in diabetic wound healing.

Chronic wounds are a common and debilitating complication for the diabetic population. It is challenging to study the development of chronic wounds in human patients; by the time it is clear that a wound is chronic, the early phases of wound healing have passed and can no longer be studied. Because of this limitation, mouse models have been employed to better understand the early phases of chronic wound formation. In the past few years, a series of reports have highlighted the importance of reactive oxygen species and bacterial biofilms in the development of chronic wounds in diabetics. We review these recent findings and discuss mouse models that are being utilized to enhance our understanding of these potentially important contributors to chronic wound formation in diabetic patients.