An EGF- and Curcumin-Co-Encapsulated Nanostructured Lipid Carrier Accelerates Chronic-Wound Healing in Diabetic Rats

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.

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Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

Molecules ◽

10.3390/molecules25153401 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3401

Author(s):

David Meléndez-Martínez ◽

Luis Fernando Plenge-Tellechea ◽

Ana Gatica-Colima ◽

Martha Sandra Cruz-Pérez ◽

José Manuel Aguilar-Yáñez ◽

...

Keyword(s):

Wound Healing ◽

Serine Proteases ◽

Chronic Wounds ◽

Chronic Wound ◽

Healing Process ◽

Wound Healing Process ◽

Major Health Problem ◽

Normal Wound Healing ◽

Alternative Sources ◽

Fibrin Clots

Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.

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Immunology of Acute and Chronic Wound Healing

Biomolecules ◽

10.3390/biom11050700 ◽

2021 ◽

Vol 11 (5) ◽

pp. 700

Author(s):

Kamila Raziyeva ◽

Yevgeniy Kim ◽

Zharylkasyn Zharkinbekov ◽

Kuat Kassymbek ◽

Shiro Jimi ◽

...

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Chronic Wound ◽

Healing Process ◽

Inflammatory Factors ◽

Wound Healing Process ◽

Macrophage Phenotype ◽

Microbial Biofilms ◽

Inflammatory Phase ◽

Persistent Inflammation

Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

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Nano-in-Micro Dual Delivery Platform for Chronic Wound Healing Applications

Micromachines ◽

10.3390/mi11020158 ◽

2020 ◽

Vol 11 (2) ◽

pp. 158 ◽

Cited By ~ 3

Author(s):

Jana Zarubova ◽

Mohammad Mahdi Hasani-Sadrabadi ◽

Lucie Bacakova ◽

Song Li

Keyword(s):

Wound Healing ◽

Network Formation ◽

Chronic Wound ◽

Wound Care ◽

Healing Process ◽

Microfluidic System ◽

Wound Healing Process ◽

Delivery Platform ◽

Endothelial Growth Factor

Here, we developed a combinatorial delivery platform for chronic wound healing applications. A microfluidic system was utilized to form a series of biopolymer-based microparticles with enhanced affinity to encapsulate and deliver vascular endothelial growth factor (VEGF). Presence of heparin into the structure can significantly increase the encapsulation efficiency up to 95% and lower the release rate of encapsulated VEGF. Our in vitro results demonstrated that sustained release of VEGF from microparticles can promote capillary network formation and sprouting of endothelial cells in 2D and 3D microenvironments. These engineered microparticles can also encapsulate antibiotic-loaded nanoparticles to offer a dual delivery system able to fight bacterial infection while promoting angiogenesis. We believe this highly tunable drug delivery platform can be used alone or in combination with other wound care products to improve the wound healing process and promote tissue regeneration.

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Preparation of W/O Hypaphorine–Chitosan Nanoparticles and Its Application on Promoting Chronic Wound Healing via Alleviating Inflammation Block

Nanomaterials ◽

10.3390/nano11112830 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2830

Author(s):

Mengting Qi ◽

Xuerui Zhu ◽

Xiaoyi Yu ◽

Min Ai ◽

Weiwei Cai ◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Chronic Wounds ◽

Chronic Wound ◽

Chitosan Nanoparticles ◽

Average Diameter ◽

Diabetic Rats ◽

Diabetic Rat ◽

Patients With Diabetes ◽

Treatment Of Wounds

Chronic wound repair is a common complication in patients with diabetes mellitus, which causes a heavy burden on social medical resources and the economy. Hypaphorine (HYP) has good anti-inflammatory effect, and chitosan (CS) is used in the treatment of wounds because of its good antibacterial effect. The purpose of this research was to investigate the role and mechanism of HYP-nano-microspheres in the treatment of wounds for diabetic rats. The morphology of HYP-NPS was observed by transmission electron microscopy (TEM). RAW 264.7 macrophages were used to assess the bio-compatibility of HYP-NPS. A full-thickness dermal wound in a diabetic rat model was performed to evaluate the wound healing function of HYP-NPS. The results revealed that HYP-NPS nanoparticles were spherical with an average diameter of approximately 50 nm. The cell experiments hinted that HYP-NPS had the potential as a trauma material. The wound test in diabetic rats indicated that HYP-NPS fostered the healing of chronic wounds. The mechanism was through down-regulating the expression of pro-inflammatory cytokines IL-1β and TNF-α in the skin of the wound, and accelerating the transition of chronic wound from inflammation to tissue regeneration. These results indicate that HYP-NPS has a good application prospect in the treatment of chronic wounds.

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A Systematic Overview of Recent Methods for Non-Contact Chronic Wound Analysis

Applied Sciences ◽

10.3390/app10217613 ◽

2020 ◽

Vol 10 (21) ◽

pp. 7613

Author(s):

Domagoj Marijanović ◽

Damir Filko

Keyword(s):

Wound Healing ◽

Global Economy ◽

Chronic Wounds ◽

Chronic Wound ◽

Healing Process ◽

Significant Rise ◽

Wound Healing Process ◽

Obesity And Diabetes ◽

Wound Assessment ◽

Analysis System

Chronic wounds or wounds that are not healing properly are a worldwide health problem that affect the global economy and population. Alongside with aging of the population, increasing obesity and diabetes patients, we can assume that costs of chronic wound healing will be even higher. Wound assessment should be fast and accurate in order to reduce the possible complications, and therefore shorten the wound healing process. Contact methods often used by medical experts have drawbacks that are easily overcome by non-contact methods like image analysis, where wound analysis is fully or partially automated. Two major tasks in wound analysis on images are segmentation of the wound from the healthy skin and background, and classification of the most important wound tissues like granulation, fibrin, and necrosis. These tasks are necessary for further assessment like wound measurement or healing evaluation based on tissue representation. Researchers use various methods and algorithms for image wound analysis with the aim to outperform accuracy rates and show the robustness of the proposed methods. Recently, neural networks and deep learning algorithms have driven considerable performance improvement across various fields, which has a led to a significant rise of research papers in the field of wound analysis as well. The aim of this paper is to provide an overview of recent methods for non-contact wound analysis which could be used for developing an end-to-end solution for a fully automated wound analysis system which would incorporate all stages from data acquisition, to segmentation and classification, ending with measurement and healing evaluation.

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Chronic Wounds: Innovations in Diagnostics and Therapeutics

Current Medicinal Chemistry ◽

10.2174/0929867324666170710120556 ◽

2019 ◽

Vol 25 (41) ◽

pp. 5772-5781 ◽

Cited By ~ 6

Author(s):

Marieke Haalboom

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Chronic Wound ◽

Current Knowledge ◽

Wound Care ◽

Healing Process ◽

Diagnostic Tools ◽

Bacterial Invasion ◽

Wound Healing Process ◽

Limited Effectiveness

Background: A major global health issue is the existence of chronic wounds. Appropriate diagnosis and treatment is essential to promote wound healing and prevent further complications. Traditional methods for treatment and diagnosis of chronic wounds have shown to be of limited effectiveness. Therefore, there is a need for the development of diagnostic and therapeutic innovations in chronic wound care. Objective: This mini-review aims to provide insight in the current knowledge of the wound healing process and the deficiencies encountered in chronic wounds, which provides a basis for the development of innovations in chronic wound care. Furthermore, promising diagnostic and therapeutic innovations will be highlighted. Methods: Literature was searched for recent articles (=<10 years) describing the current knowledge about the wound healing process and chronic wounds. The most promising diagnostic and therapeutic innovations were gathered from articles published in the past 5 years. Results/Conclusion: Wound healing is a well-organized process consisting of four phases: coagulation, inflammation, proliferation and wound remodelling. Chronic wounds often stagnate in the inflammatory phase and/or experience an impaired proliferative phase. This mini-review has demonstrated that increased knowledge about the processes involved in wound healing has paved the way for the development of new diagnostic tools and treatments for chronic wounds. Increased knowledge about bacterial invasion and infection in has encouraged researchers to develop diagnostic tools to help clinicians detect these phenomena appropriately and in time. Other researchers have shown that they are able to design/extract biochemical compounds that intervene in the disrupted healing processes in chronic wounds.

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The use of a rat model to evaluate the in vivo toxicity and wound healing activity of selected Combretum and Terminalia (Combretaceae) species extracts

Onderstepoort Journal of Veterinary Research ◽

10.4102/ojvr.v77i1.2 ◽

2010 ◽

Vol 77 (1) ◽

Cited By ~ 4

Author(s):

Peter Masoko ◽

Jackie Picard ◽

Jacobus N. Eloff

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Fungal Infections ◽

Tissue Injury ◽

Healing Process ◽

The Body ◽

Wound Healing Process ◽

Leaf Extracts ◽

Significant Difference

Wound healing is a fundamental response to tissue injury and several natural products have been shown to accelerate the healing process. The present study was undertaken to determine the safety and efficacy of the topical treatment of acetone leaf extracts of Combretum imberbe, Combretum nelsonii,Combretum albopuntactum and Terminalia sericea based on their in vitro antimicrobial activity. Four circular full-thickness skin wounds were made on the backs of eight anaesthetised Wistar rats using aseptic techniques. The treatments were administrated topically using 10% and 20% concentrations of each extract in aqueous cream in separate treatments. Indications of erythema, exudate, crust formation,swelling and ulceration were used to determine the wound healing process. All of the wounds closed completely within 17 days. Throughout the experiment, a subcutaneous probe was used to determine that the body temperature and body weight of the rats were within the normal range. C. imberbe and C. nelsonii extracts accelerated wound healing, but there was no significant difference in wound contraction using 10% and 20% concentrations of the extracts in cream. The results also showed the potential usefulness of this model to measure accelerating wound healing.The extracts could perhaps overcome defects associated with healing failure in chronic wounds and prevent secondary bacterial and fungal infections.

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Wound Healing in the Golden Agers: What We Know and the Possible Way Ahead

The International Journal of Lower Extremity Wounds ◽

10.1177/15347346211037841 ◽

2021 ◽

pp. 153473462110378

Author(s):

Aakansha Giri Goswami ◽

Somprakas Basu ◽

Vijay Kumar Shukla

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Wound Care ◽

Financial Burden ◽

Healing Process ◽

The Elderly ◽

Wound Healing Process ◽

Impaired Wound Healing ◽

Age Related

While “population aging” is an accomplishment that deserves acclamation, it is in itself a tremendous challenge. Age-related skin changes, impaired wound healing, and concurrent comorbidities are the deadly triad that contribute most to the development of nonhealing chronic wounds in the elderly. This imposes enormous medical, social, and financial burden. With the rising trend in the aging population, this problem is likely to exacerbate unless multidisciplinary, rapt wound care strategies are developed. The last decade was dedicated to understand the basic biology underlying the wound healing process but most in vitro and animal model studies translated poorly to human conditions. Forthcoming, the focus is on the development of diagnostic and therapeutic strategies to improve healing in this vulnerable age group. Further, understanding the complex pathobiology of cellular senescence and wound healing process is required to develop focused therapy for these “problem wounds” in the elderly.

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Wound dressings: curbing inflammation in chronic wound healing

Emerging Topics in Life Sciences ◽

10.1042/etls20200346 ◽

2021 ◽

Author(s):

Davide Vincenzo Verdolino ◽

Helen A. Thomason ◽

Andrea Fotticchia ◽

Sarah Cartmell

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Chronic Wound ◽

Wound Care ◽

Healing Process ◽

Standard Of Care ◽

The Elderly ◽

Wound Dressings ◽

Wound Healing Process

Chronic wounds represent an economic burden to healthcare systems worldwide and a societal burden to patients, deeply impacting their quality of life. The incidence of recalcitrant wounds has been steadily increasing since the population more susceptible, the elderly and diabetic, are rapidly growing. Chronic wounds are characterised by a delayed wound healing process that takes longer to heal under standard of care than acute (i.e. healthy) wounds. Two of the most common problems associated with chronic wounds are inflammation and infection, with the latter usually exacerbating the former. With this in mind, researchers and wound care companies have developed and marketed a wide variety of wound dressings presenting different compositions but all aimed at promoting healing. This makes it harder for physicians to choose the correct therapy, especially given a lack of public quantitative data to support the manufacturers’ claims. This review aims at giving a brief introduction to the clinical need for chronic wound dressings, focusing on inflammation and evaluating how bio-derived and synthetic dressings may control excess inflammation and promote healing.

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AUTOLOGOUS PLATELET - RICH PLASMA (PRP) THERAPY AND CHANGEMENTS OF TOPICAL BIOLOGICAL MARKERS (EGF, VEGF AND MMP12) OF CHRONIC WOUNDS

Tạp chí Y học Việt Nam ◽

10.51298/vmj.v506i1-2.973 ◽

2021 ◽

Vol 506 (1-2) ◽

Author(s):

Nguyen Ngoc Tuan ◽

Nguyen Tran Ngoc Tu ◽

Nguyen Tien Dung

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Chronic Wound ◽

Platelet Rich Plasma ◽

Healing Process ◽

Wound Healing Process ◽

Elisa Technique ◽

Autologous Platelet Rich Plasma ◽

Autologous Platelet

Objective: Our aim was to evaluate topical EGF, VEGF, MMP12 concentrations of chronic wounds which after Autologous Platelet - Rich Plasma(PRP) therapy. Methods: The study conducted a descriptive longitudinal study at the Wound Healing Center of the Vietnam National Burn Hospital from 11/2018 to 2/2020. 24 patients with chronic wounds and aged 18 years old or older were enrolled in this study. These patients were injected autologous PRP at wound bed. We biopsied chronic wound bed tissue for evaluating EGF, VEGF and MMP12 by the Elisa technique at the first, second and third week of follow-up. Results: After PRP therapy, topical EGF and VEGF concentration increased after 1 week of treatment. MMP12 concentraiton significantly reduced compaired to before PRP therapy. Conclusion: In addition to PRP therapy had a beneficial effect on cutaneous regeneration and wound healing of the chronic wound. The autologous PRP promoted the wound healing process byincreating topical EGF and VEGF, reducing MMP12 which known as a pro-inflammatiory mediator.

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