Chronic Wounds: Innovations in Diagnostics and Therapeutics

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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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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Identifying New Pathways and Targets for Wound Healing and Therapeutics from Natural Sources

Current Drug Delivery ◽

10.2174/1567201818666210111101257 ◽

2021 ◽

Vol 18 ◽

Author(s):

Xinchi Feng ◽

Jinsong Hao

Keyword(s):

Wound Healing ◽

Molecular Mechanisms ◽

Chronic Wounds ◽

Wound Care ◽

Healing Process ◽

Unmet Need ◽

Wound Dressings ◽

Wound Healing Process ◽

Natural Sources ◽

Viable Approach

: Chronic wounds remain a significant public problem and the development of wound treatments has been a research focus for the past few decades. Despite advances in the products derived from endogenous substances involved in a wound healing process (e.g. growth factors, stem cells, and extracellular matrix), effective and safe wound therapeutics are still limited. There is an unmet need to develop new therapeutics. Various new pathways and targets have been identified and could become a molecular target in designing novel wound agents. Importantly, many existing drugs that target these newly identified pathways could be repositioned for wound therapy, which will facilitate fast translation of research findings to clinical applications. This review discusses the newly identified pathways/targets and their potential uses in the development of wound therapeutics. Some herbs and amphibian skins have been traditionally used for wound repairs and their active ingredients have been found to act in these new pathways. Hence, screening these natural products for novel wound therapeutics remains a viable approach. The outcomes of wound care using natural wound therapeutics could be improved if we can better understand their cellular and molecular mechanisms and fabricate them in appropriate formulations, such as using novel wound dressings and nano-engineered materials. Therefore, we also provide an update on the advances in the wound therapeutics from natural sources. Overall, this review offers new insights into novel wound therapeutics.

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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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Bionanomaterials: Advancements in Wound Healing and Tissue Regeneration

10.5772/intechopen.97298 ◽

2021 ◽

Author(s):

Priyanka Chhabra ◽

Kajol Bhati

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Wound Care ◽

Health Care Organization ◽

Healing Process ◽

Volume Ratio ◽

Wound Healing Process ◽

Care Organization ◽

Complex Process ◽

High Degree

Abnormal wound healing represents a major healthcare issue owing to upsurge number of trauma and morbid physiology which ultimately posed a healthcare burden on patient, society and health care organization. A wound healing is a complex process so effective management of chronic wounds is often hard. Recently in addition to many conventional wound treatment’s advances in bionanomaterial are attaining much attention in wound care and skin tissue engineering. Bionanomaterials are biomolecule-based nanocomposite synthesized by plants, microbes and animals which possess high degree of biocompatibility, biodegradability, non-toxicity and bioactive assets. Bioactive assets like antimicrobial, immune modulatory, cell proliferation and angiogenesis of biomolecules forms fortunate microenvironment for the wound healing process. Nature has provided us with a significant set of biomolecules like chitosan, hyaluronic acid, collagen, cellulose, silk fucoidan etc. have been exploited to construct engineered bionanomaterials. These biopolymeric nanomaterials are currently researched comprehensively as they have higher surface to volume ratio and high chemical affinity showing a promising augmentation of deadly wounds. In this chapter we aimed to highlight the biological sources and bioengineering approaches adapted for biopolymers so they facilitate wound healing process.

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

Molecules ◽

10.3390/molecules25204610 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4610

Author(s):

Hye-Jin Lee ◽

Moses Jeong ◽

Young-Guk Na ◽

Sung-Jin Kim ◽

Hong-Ki Lee ◽

...

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Chronic Wound ◽

Healing Process ◽

Double Emulsion ◽

Average Diameter ◽

Diabetic Rats ◽

Wound Healing Process ◽

Nanostructured Lipid Carrier

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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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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Quercetin and its Natural Sources in Wound Healing Management

Current Medicinal Chemistry ◽

10.2174/0929867325666180713150626 ◽

2019 ◽

Vol 26 (31) ◽

pp. 5825-5848 ◽

Cited By ~ 6

Author(s):

Nicoletta Polera ◽

Mariateresa Badolato ◽

Filomena Perri ◽

Gabriele Carullo ◽

Francesca Aiello

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Chronic Wounds ◽

Wound Care ◽

Biological Activities ◽

Healing Process ◽

Wound Management ◽

Wound Healing Process ◽

Impaired Wound Healing ◽

Care Research

Giving a glance to the report of Wound Care Market by Product updated in 2017, we can see that wound care market is expected to reach USD 22.01 billion by 2022 from USD 18.35 billion at a CAGR of 3.7%. Numerous factors are driving the growth of this market, including the increasing prevalence of chronic wounds and acute wounds, increasing aged population, rising R&D activities and advancement in the field of wound care research. Advanced wound management products are accounted for the largest market share in 2017. These evidences mean that the wound care research represents a Clinical Emergency other than an interesting Marketing tool. Drug therapies so far fight efficaciously with the opportunistic pathologies derived from chronic wounds, although an unsolved challenge is still finding a useful remedy to correct the impaired wound healing process and overcome the chronic wound state, to avoid bacterial rising and severe pain. Traditional medicinal plants have been widely used in the management of wounds and different plant extracts have been evaluated for their wound healing properties through both in vitro and in vivo studies. Their phytochemical components in particular quercetin, contribute to their remedial properties in wound repair. Quercetin has important biological activities related to the improvement of the wound healing process. The present review discusses and focuses on the latest findings of the wound healing properties of quercetin, alone or as a part of plant extract, and its role as a new frontier in wound repair.

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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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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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