Human-microorganism mutualism theory: Possible mechanisms for the delayed chronic wound healing process

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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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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Ekek anti mikroba terapi larva

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.8.1.2016.12332 ◽

2016 ◽

Vol 8 (1) ◽

Author(s):

Sunny Wangko

Keyword(s):

Wound Healing ◽

Chronic Wound ◽

Healing Process ◽

Wound Management ◽

Wound Healing Process ◽

Healing Wounds ◽

Chronic Wound Management ◽

Very High ◽

Anti Inflammation ◽

Larval Therapy

Abstract: Chronic wound is still a world-wide problem that spends a very high cost related to its management and treatment. Although there are a lot of promising studies about wound healing process, the prevalence and incidence of chronic wound and its complications are still high. Conventionally, the management of chronic wound consists of surgical debridement, manual irrigation, dressing, and antimicrobial therapy (topical and/or systemic). It is accepted that microbial biofilm and its complexity play important roles in non-healing wounds. This biofilm consists of polymicrobial colonies embedded in exopolymeric matrix produced by the biofilm itself and has a high tolerance to host defence mechanisme, antibiotics, and antiseptics. Larval therapy has been approved by FDA to be used in chronic wound management. It has antimicrobial effects besides its other effects on wound healing inter alia mechanical debridement, anti-inflammation, angiogenesis, and destabilization of biofilm enzymes. Further studies are needed to explore the effects of larval therapy, especially its excretion/secretion components, so that it can be applicated more aesthetically.Keywords: chronic wound, wound healing process, biofilm, larval therapyAbstrak: Luka kronis merupakan masalah kesehatan di seluruh dunia yang telah memboroskan biaya cukup tinggi. Walaupun telah terjadi kemajuan dan pemahaman mengenai penyembuhan luka, prevalensi dan insidensi luka kronis dan komplikasinya tetap meningkat pesat. Secara konvensional, perawatan luka kronis terdiri dari debrideman, irigasi manual, dressing untuk mempertahankan kelembaban, dan terapi antimikroba (topikal dan atau sistemik). Adanya biofilm mikroba serta kompleksitasnya pada luka kronis telah disepakati sebagai salah satu kunci gagalnya penyembuhan luka. Biofilm mikroba terdiri dari koloni-koloni mikroorganisme polimikrobial terkemas dalam matriks eksopolimerik yang diproduksi olehnya sendiri dan memiliki toleransi tinggi terhadap pertahanan pejamu (host), antibiotik, dan antiseptik. Terapi larva telah diterima oleh FDA dan telah terbukti berefek antimikroba disamping efek lainnya terhadap penyembuhan luka, antara lain: debrideman mekanis, anti-inflamasi, angiogenesis, dan destabilisasi enzim biofilm pada luka. Studi lanjut diperlukan untuk mengeksplorasi efek terapi larva terutama komponen ekskresi/skresi larva terhadap penyembuhan luka agar dapat diaplikasikan secara lebih estetik.Kata kunci: luka kronis, penyembuhan luka, biofilm, terapi larva

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TERAPI LARVA PADA LUKA KRONIS TERBUKA

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.7.1.2015.7289 ◽

2015 ◽

Vol 7 (1) ◽

Author(s):

Sunny Wangko

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Chronic Wound ◽

Healing Process ◽

Bioactive Molecules ◽

Wound Management ◽

Wound Healing Process ◽

Beneficial Effects ◽

Infected Wounds ◽

Larval Therapy

Abstract: The usage of larvae in wound treatment has been known across the centuries in different countries. However, larval therapy is offered when the conventional therapy has failed in the management of chronic, infected wounds. Concerning the larval therapy, it was presumed that the wound healing was due to the mechanical debridement effect of the larval movement and of their hooks. To date, a variety of study reports reveals that there are several beneficial effects of the larval therapy, inter alia: secretion/excretion of larvae contains enzymes, growth factors, and cytokines that collaborate in the wound healing process. The bioactive molecules in the secretion/excretion of the larvae has to be further studied and to be developed, therefore, they can be applied in the wound management efficiently and economically. Keywords: larval therapy, chronic wound, healing process. Abstrak: Walaupun pemanfaatan larva pada luka kronis telah sangat lama dikenal di berbagai negara, terapi larva umumnya digunakan bila terapi konvensional telah gagal. Awalnya diduga bahwa efek debridemen mekanis oleh gerakan larva dan kaitnya yang paling berperan. Dewasa ini, laporan berbagi studi telah mengungkapkan bahwa larva menyekresi dan menyintesis berbagai bahan baik berupa enzim, sitokin, dan growth factors yang turut berperan dalam proses penyembuhan luka. Adanya molekul bioaktif dalam ekskresi dan sekresi larva perlu diteliti dan dikembangkan agar dapat diaplikasikan dengan lebih efisien dan ekonomis. Kata kunci: terapi larva, luka kronis, penyembuhan luka.

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A Review on Revolutionary Natural Biopolymer-Based Aerogels for Antibacterial Delivery

Antibiotics ◽

10.3390/antibiotics9100648 ◽

2020 ◽

Vol 9 (10) ◽

pp. 648 ◽

Cited By ~ 1

Author(s):

Esam Bashir Yahya ◽

Fauziah Jummaat ◽

A. A. Amirul ◽

A. S. Adnan ◽

N. G. Olaiya ◽

...

Keyword(s):

Mechanical Properties ◽

Wound Healing ◽

Metallic Nanoparticles ◽

Biomedical Applications ◽

Chronic Wound ◽

Healing Process ◽

Wound Healing Process ◽

Physical Chemical ◽

The Relationship ◽

Plants Extract

A biopolymer-based aerogel has been developed to become one of the most potentially utilized materials in different biomedical applications. The biopolymer-based aerogel has unique physical, chemical, and mechanical properties and these properties are used in tissue engineering, biosensing, diagnostic, medical implant and drug delivery applications. Biocompatible and non-toxic biopolymers such as chitosan, cellulose and alginates have been used to deliver antibiotics, plants extract, essential oils and metallic nanoparticles. Antibacterial aerogels have been used in superficial and chronic wound healing as dressing sheets. This review critically analyses the utilization of biopolymer-based aerogels in antibacterial delivery. The analysis shows the relationship between their properties and their applications in the wound healing process. Furthermore, highlights of the potentials, challenges and proposition of the application of biopolymer-based aerogels is explored.

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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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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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