scholarly journals Hyperglycemia-Induced Changes in Hyaluronan Contribute to Impaired Skin Wound Healing in Diabetes: Review and Perspective

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Sajina Shakya ◽  
Yan Wang ◽  
Judith A. Mack ◽  
Edward V. Maytin
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Glucose Levels ◽  
Cytokine Levels ◽  
The Status ◽  
Perivascular Area ◽  
Induced Changes ◽  
Cutaneous Blood

Ulcers and chronic wounds are a particularly common problem in diabetics and are associated with hyperglycemia. In this targeted review, we summarize evidence suggesting that defective wound healing in diabetics is causally linked, at least in part, to hyperglycemia-induced changes in the status of hyaluronan (HA) that resides in the pericellular coat (glycocalyx) of endothelial cells of small cutaneous blood vessels. Potential mechanisms through which exposure to high glucose levels causes a loss of the glycocalyx on the endothelium and accelerates the recruitment of leukocytes, creating a proinflammatory environment, are discussed in detail. Hyperglycemia also affects other cells in the immediate perivascular area, including pericytes and smooth muscle cells, through exposure to increased cytokine levels and through glucose elevations in the interstitial fluid. Possible roles of newly recognized, cross-linked forms of HA, and interactions of a major HA receptor (CD44) with cytokine/growth factor receptors during hyperglycemia, are also discussed.

scholarly journals The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 457
Author(s):  
Andreu Blanquer ◽  
Jana Musilkova ◽  
Elena Filova ◽  
Johanka Taborska ◽  
Eduard Brynda ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Chronic Wounds ◽  
Human Keratinocytes ◽  
Skin Wound ◽  
Platelet Lysate ◽  
Therapeutic Approaches ◽  
Skin Wound Healing ◽  
New Therapeutic Approaches ◽  
Proliferation And Differentiation

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

scholarly journals EFFECTS OF PROBIOTICS SUPPLEMENTATION ON SKIN WOUND HEALING IN DIABETIC RATS

2020 ◽  
Vol 33 (1) ◽  
Author(s):  
Letícia Fuganti CAMPOS ◽  
Eliane TAGLIARI ◽  
Thais Andrade Costa CASAGRANDE ◽  
Lúcia de NORONHA ◽  
Antônio Carlos L. CAMPOS ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Type I Collagen ◽  
Chronic Wounds ◽  
Skin Wound ◽  
Diabetic Rats ◽  
Control Group ◽  
Type I ◽  
Collagen Deposition ◽  
Skin Wound Healing

ABSTRACT Background: Chronic wounds in patients with Diabetes Mellitus often become incurable due to prolonged and excessive production of inflammatory cytokines. The use of probiotics modifies the intestinal microbiota and modulates inflammatory reactions. Aim: To evaluate the influence of perioperative supplementation with probiotics in the cutaneous healing process in diabetic rats. Methods: Forty-six rats were divided into four groups (C3, P3, C10, P10) according to the treatment (P=probiotic or C=control, both orally administered) and day of euthanasia, 3rd or 10th postoperative days. All rats were induced to Diabetes Mellitus 72 h before starting the experiment with alloxan. Supplementation was initiated five days before the incision and maintained until euthanasia. Scalpel incision was guided by a 2x2 cm mold and the wounds were left to heal per second-intention. The wounds were digitally measured. Collagen densitometry was done with Picrosirius Red staining. Histological parameters were analyzed by staining by H&E. Results: The contraction of the wound was faster in the P10 group which resulted in a smaller scar area (p=0.011). There was an increase in type I collagen deposition from the 3rd to the 10th postoperative day in the probiotic groups (p=0.016), which did not occur in the control group (p=0.487). The histological analysis showed a better degree of healing in the P10 group (p=0.005), with fewer polymorphonuclear (p<0.001) and more neovessels (p=0.001). Conclusions: Perioperative supplementation of probiotics stimulates skin wound healing in diabetic rats, possibly due to attenuation of the inflammatory response and increased neovascularization and type I collagen deposition.

scholarly journals Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

2020 ◽  
Vol 8 ◽  
Author(s):  
Pengcheng Xu ◽  
Yaguang Wu ◽  
Lina Zhou ◽  
Zengjun Yang ◽  
Xiaorong Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Platelet Rich Plasma ◽  
Skin Wound ◽  
Local Inflammation ◽  
Skin Wound Healing

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

scholarly journals From Inflammation to Cutaneous Repair: Topical Application of Lupeol Improves Skin Wound Healing in Rats by Modulating the Cytokine Levels, NF-κB, Ki-67, Growth Factor Expression, and Distribution of Collagen Fibers

2020 ◽  
Vol 21 (14) ◽  
pp. 4952 ◽  
Author(s):  
Fernando Pereira Beserra ◽  
Lucas Fernando Sérgio Gushiken ◽  
Ana Júlia Vieira ◽  
Danilo Augusto Bérgamo ◽  
Patrícia Luísa Bérgamo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Growth Factor ◽  
Skin Wound ◽  
Collagen Fibers ◽  
Skin Wound Healing ◽  
Ki 67 ◽  
Healing Effect ◽  
Cytokine Levels ◽  
Wound Healing Effect

Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1β, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-β1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases.

scholarly journals Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration

2019 ◽  
Vol 116 (19) ◽  
pp. 9443-9452 ◽  
Author(s):  
Dongqing Li ◽  
Lara Kular ◽  
Manika Vij ◽  
Eva K. Herter ◽  
Xi Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Noncoding Rna ◽  
Chronic Wounds ◽  
Ex Vivo ◽  
Dna Methyltransferases ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Protein Coding ◽  
Keratinocyte Migration ◽  
Gene Expression Control

An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-β signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed “wound and keratinocyte migration-associated lncRNA 1” (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds.

scholarly journals Immunomodulatory Properties of Host Defence Peptides in Skin Wound Healing

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 952
Author(s):  
Marija Petkovic ◽  
Michelle Vang Mouritzen ◽  
Biljana Mojsoska ◽  
Håvard Jenssen
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Skin Wound ◽  
Host Defence ◽  
Large Network ◽  
Skin Wound Healing ◽  
Signalling Molecules ◽  
Inflammatory Conditions ◽  
Peripheral Sensory

Cutaneous wound healing is a vital biological process that aids skin regeneration upon injury. Wound healing failure results from persistent inflammatory conditions observed in diabetes, or autoimmune diseases like psoriasis. Chronic wounds are incurable due to factors like poor oxygenation, aberrant function of peripheral sensory nervature, inadequate nutrients and blood tissue supply. The most significant hallmark of chronic wounds is heavily aberrant immune skin function. The immune response in humans relies on a large network of signalling molecules and their interactions. Research studies have reported on the dual role of host defence peptides (HDPs), which are also often called antimicrobial peptides (AMPs). Their duality reflects their potential for acting as antibacterial peptides, and as immunodulators that assist in modulating several biological signalling pathways related to processes such as wound healing, autoimmune disease, and others. HDPs may differentially control gene regulation and alter the behaviour of epithelial and immune cells, resulting in modulation of immune responses. In this review, we shed light on the understanding and most recent advances related to molecular mechanisms and immune modulatory features of host defence peptides in human skin wound healing. Understanding their functional role in skin immunity may further inspire topical treatments for chronic wounds.

Roles of lactoferrin on skin wound healing1This article is part of Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.

2012 ◽  
Vol 90 (3) ◽  
pp. 497-503 ◽  
Author(s):  
Yoshiharu Takayama ◽  
Reiji Aoki
Keyword(s):  
Wound Healing ◽  
Granulation Tissue ◽  
Chronic Wounds ◽  
Peer Review Process ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Inflammatory Phase ◽  
Complex Biological Process ◽  
Extracellular Matrix Components

Skin wound healing is a complex biological process that requires the regulation of different cell types, including immune cells, keratinocytes, fibroblasts, and endothelial cells. It consists of 5 stages: hemostasis, inflammation, granulation tissue formation, re-epithelialization, and wound remodeling. While inflammation is essential for successful wound healing, prolonged or excess inflammation can result in nonhealing chronic wounds. Lactoferrin, an iron-binding glycoprotein secreted from glandular epithelial cells into body fluids, promotes skin wound healing by enhancing the initial inflammatory phase. Lactoferrin also exhibits anti-inflammatory activity that neutralizes overabundant immune response. Accumulating evidence suggests that lactoferrin directly promotes both the formation of granulation tissue and re-epithelialization. Lactoferrin stimulates the proliferation and migration of fibroblasts and keratinocytes and enhances the synthesis of extracellular matrix components, such as collagen and hyaluronan. In an in vitro model of wound contraction, lactoferrin promoted fibroblast-mediated collagen gel contraction. These observations indicate that lactoferrin supports multiple biological processes involved in wound healing.

Regenerative properties of recombinant human erythropoetin in wound healing

2021 ◽  
Vol 9-10 (219-220) ◽  
pp. 52-58
Author(s):  
Mariya Dmitriyeva ◽  
◽  
Medet Toleubayev ◽  
Saken Kozhakhmetov ◽  
Nurbek Igissinov ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Regeneration ◽  
Search Strategy ◽  
Chronic Wounds ◽  
Skin Wound ◽  
Clinical Use ◽  
Wound Treatment ◽  
Skin Wound Healing ◽  
Positive Effects ◽  
Single Mechanism

Erythropoietin is the main stimulator of erythropoiesis, but erythropoietin also has non-hematopoietic effects. The recent data show the positive effects of erythropoietin on tissue regeneration. This review highlights the pathophysiological mechanisms of erythropoietin at different stages of tissue regeneration, and possible clinical applications in wound healing. Aim. Study of the world experience of using erythropoietin for the treatment of experimental wounds and the experience of clinical use for the treatment of patients with chronic wounds. Material and methods. The literature was searched in the databases: Pubmed, EMBASE and Google Scholar using the keywords: "Erythropoietin", "EPO", "wounds", "wound treatment", "VEGF", "re-epithelialization", "skin". The search depth was 20 years. When compiling a search strategy, the use of the title of articles, abstracts, as well as conference materials in English, Russian, Kazakh languages was used. Experimental original articles, narrative reviews were included in this review. Results and discussion. To date, there is a sufficient amount of experimental data confirming the effectiveness of EPO on the pathomorphological processes of skin wound healing, but it is still impossible to determine a single mechanism or cellular function that could be responsible for the ability of tissue regeneration mediated by EPO. Conclusion. Research into the ability of erythropoietin to improve tissue regeneration may lead to new insights into this growth hormone for its regular clinical use in patients. Key words: EPO, wound healing, VEGF, reepithelization, skin.

scholarly journals Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 735 ◽  
Author(s):  
Erika Maria Tottoli ◽  
Rossella Dorati ◽  
Ida Genta ◽  
Enrica Chiesa ◽  
Silvia Pisani ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Healing Process ◽  
Skin Wound ◽  
Skin Regeneration ◽  
Bioactive Molecules ◽  
Wound Healing Process ◽  
Skin Wound Healing

Skin wound healing shows an extraordinary cellular function mechanism, unique in nature and involving the interaction of several cells, growth factors and cytokines. Physiological wound healing restores tissue integrity, but in many cases the process is limited to wound repair. Ongoing studies aim to obtain more effective wound therapies with the intention of reducing inpatient costs, providing long-term relief and effective scar healing. The main goal of this comprehensive review is to focus on the progress in wound medication and how it has evolved over the years. The main complications related to the healing process and the clinical management of chronic wounds are described in the review. Moreover, advanced treatment strategies for skin regeneration and experimental techniques for cellular engineering and skin tissue engineering are addressed. Emerging skin regeneration techniques involving scaffolds activated with growth factors, bioactive molecules and genetically modified cells are exploited to overcome wound healing technology limitations and to implement personalized therapy design.

scholarly journals ROS-Degradable Polythioketal Urethane Foam Dressings to Promote Porcine Skin Wound Repair

2021 ◽  
Author(s):  
Prarthana Patil ◽  
Katherine A Russo ◽  
Joshua T McCune ◽  
Alonda C Pollins ◽  
Matthew A Cottom ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Degradation Products ◽  
Skin Wound ◽  
Foreign Body Response ◽  
Skin Wound Healing ◽  
Tissue Integration ◽  
Wound Matrix

Impaired skin healing and progression into chronic wounds is a prevalent and growing medical problem. Porous, resorbable biomaterials can be used as temporary substrates placed into skin defects to support cell infiltration, neo-tissue formation, and remodeling of nonhealing wounds. Naturally-derived biomaterials have promising healing benefits, but their low mechanical properties and exuberant costs limit their performance and use. Synthetic materials can be affordably manufactured and tuned across a broader range of physiochemical properties, but opportunities remain for tailoring them for ideal host immune and regenerative responses. Polyesters are the most clinically-tested class of synthetic biomaterials, but their hydrolysis releases acidic degradation products that can cause autocatalytic degradation processes that are poorly controlled and are not tied to cellular or other biologic activities. Here, we systemically explored a series of ROS-degradable polythioketal (PTK) urethane (UR) foams with varied hydrophilicity as an alternative class of synthetic biomaterials for wound healing. It was found that the most hydrophilic PTK-UR variant, which had 7 ethylene glycol (EG7) repeats flanking each side of each thioketal bond, had the highest ROS reactivity of the PTK-URs tested. In an in vivo porcine excisional skin wound healing model, hydrophilic EG7 PTK-UR foams more effectively promoted tissue integration, ECM deposition, and re-epithelialization of full-thickness skin wound compared to more hydrophobic PTK-UR variants. Resolution of type 1 inflammation and lower foreign body response to scaffold remnants was also observed for EG7 versus more hydrophobic PTK-UR scaffolds. Finally, porcine wound healing studies showed that EG7 PTK-UR foams had similar wound healing response to a collagen-based clinical gold standard product, Integra Bilayer Wound Matrix (BWM), while outperforming polyester UR foam-based NovoSorb Biodegradable Temporizing Matrix (BTM) with respect to increased ECM production, vascularization, and biomaterial-associated immune phenotype. In sum, PTK-UR foams warrant further development toward a new class of synthetic biomaterial foams for skin wound healing applications.

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