Regenerative properties of recombinant human erythropoetin in wound healing

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.

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

Nanomaterials ◽

10.3390/nano11020457 ◽

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.

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EFFECTS OF PROBIOTICS SUPPLEMENTATION ON SKIN WOUND HEALING IN DIABETIC RATS

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-672020190001e1498 ◽

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.

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

Burns & Trauma ◽

10.1093/burnst/tkaa028 ◽

2020 ◽

Vol 8 ◽

Cited By ~ 1

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.

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Collagen membranes for skin wound repair: A systematic review

Journal of Biomaterials Applications ◽

10.1177/0885328220980278 ◽

2020 ◽

pp. 088532822098027

Author(s):

Tiago Akira Tashiro Araujo ◽

Matheus Cruz Almeida ◽

Ingrid Avanzi ◽

Julia Parisi ◽

Abdias Fernando Simon Sales ◽

...

Keyword(s):

Systematic Review ◽

Wound Healing ◽

Healing Process ◽

Biological Tissues ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing ◽

Efficient Treatment ◽

Positive Effects ◽

Collagen Membranes

Membranes or skin dressing are common treatments for skin wound injuries, collagen being one the most effective materials for their manufacturing. Many different sources of collagen with diverse methods of extraction and processing have been used, with evidence of positive effects on the stimulation of skin wound healing. In spite of these factors, there is still limited understanding of the interaction between collagen membranes and biological tissues, especially due to the series of different types of collagen origin. In this context, this study aimed to conduct a systematic review of the available literature examining the effect of various collagen membranes for accelerating skin wound healing in experimental animal models and clinical trials. The present review was performed from March to May of 2020 searching in two databases (PubMed and Scopus). The following Medical Subject Headings (MeSH) descriptors were used: “collagen”, “dressing”, “membranes”, “skin” and “wound”. After the eligibility assessment, 16 studies were included and analyzed. The studies demonstrated that collagen was obtained predominantly from bovine and porcine sources, by acetic acid and/or enzyme dissolution. Additionally, most of the studies demonstrated that the membranes were processed mainly by freeze-drying or lyophilization methods. All the in vivo and clinical trial studies evidenced positive outcomes in the wound healing process, thus confirming that collagen membranes are one of the most efficient treatment for skin wounds, highlighting the enormous potential of this biomaterial to be used for skin tissue engineering purposes.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1814097116 ◽

2019 ◽

Vol 116 (19) ◽

pp. 9443-9452 ◽

Cited By ~ 10

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.

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Amelogenins and their effects on the wound healing of skin and oral mucous membrane

Journal of Face Aesthetics ◽

10.20883/jofa.3 ◽

2018 ◽

Vol 1 (1) ◽

pp. 31-36

Author(s):

Sylwia Klewin‑Steinböck ◽

Marzena Wyganowska‑Świątkowska

Keyword(s):

Wound Healing ◽

Mucous Membrane ◽

Tissue Regeneration ◽

Degradation Products ◽

Skin Wound ◽

Periodontal Surgery ◽

Skin Wound Healing ◽

Guide Tissue Regeneration ◽

Oral Mucous Membrane ◽

Enamel Mineralization

Amelogenins are a mixture of hydrophobic proteins that are the major organic components of developing enamel. The main functions of the amelogenins and their degradation products are structural roles in creating the space and environment for promoting enamel mineralization. They are used in periodontal surgery to guide tissue regeneration. Based on clinical evidences that amelogenins positively affect the healing of periodontium tissue new application for amelogenins have been suggested. Conducted research confirmed that amelogenins can be used in skin wound healing.

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Immunomodulatory Properties of Host Defence Peptides in Skin Wound Healing

Biomolecules ◽

10.3390/biom11070952 ◽

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.

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

International Journal of Cell Biology ◽

10.1155/2015/701738 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 32

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.

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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.

Biochemistry and Cell Biology ◽

10.1139/o11-054 ◽

2012 ◽

Vol 90 (3) ◽

pp. 497-503 ◽

Cited By ~ 26

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.

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