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0INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
FROM DRESSINGS TO NANOTECHNOLOGY: A COMPREHENSIVE REVIEW OF WOUND HEALING
TECHNIQUE
1Ayeza Sarwar Kalam, 2Mohd. Mursal, 3Sahil Hussain, 4Alina Khan, 5Arun Kumar
1Student, Faculty of Pharmacy, Integral University, Kursi Road, Lucknow -226026, Uttar
Pradesh, India
2Postgraduate Research Scholar, Department of Pharmacy, Integral university, Kursi Road
Lucknow-226026, Uttar Pradesh, India 3PhD Research Scholar, College of Health and Life Sciences, Hamad Bin Khalifa University,
Doha, Qatar
4Postgraduate Research Scholar, Department of Toxicology and Medical Elementology, Jamia
Hamdard , New Delhi -110062 5Associate Professor, Department of Pharmaceutical Chemistry, Faculty of Pharmacy Integral university, Kursi Road Lucknow-226026, Uttar Pradesh, India https://doi.org/10.5281/zenodo.13842046
Abstract. The intricacy of wound healing is influenced by the clinician's capacity to identify different healing stages, alongside considerations such as the patient's overall health and nutritional status. Understanding the fundamental physiology of wound healing is crucial for delivering effective therapy. A major driver behind the development of replacement techniques is the constant pressure to enhance the efficacy of wound healing procedures. This review primarily focuses on overseeing wound healing, spanning from its initiation to the application of healing treatments. The predominant traditional approach to healing is described, along with its major traits and limits. New and intriguing methods are offered, with an emphasis on distinctive traits and action processes. This article delves into the primary factors influencing the healing of cutaneous wounds, examining potential cellular and molecular mechanisms at play.
Keywords: wound, skin, inflammation, healing, infection, remodelling.
Introduction
The biggest organ in vertebrates, the skin covers the entire body's surface area and accounts for 10% of body mass due to its capacity to repair and regenerate itself. By acting as a crucial barrier between the inside and outside environments, it holds a pivotal function in defense and survival. A wound causes the skin's normal anatomical structure and structural integrity to be disturbed [1]. The orchestrated and dynamic process of tissue repair, recognized as wound healing involves interactions between many cell types, chemokines, growth factors, and cytokines. When this system malfunctions, excessive granulation tissue production or chronic, non-healing wounds may develop, which could stop the chronic inflammatory phase from progressing. Repairing, restoring, and regenerating damaged tissues and cells is the aim of the emerging, interdisciplinary field of biomedical study known as "regenerative medicine.". To facilitate the healing of wounds the borders of a surgical or lacerating wound are closely approximated using clips, sutures, or skin adhesives [2]. When the edges of the wound cannot be approached, secondary intention wound healing takes place. If the wound is left untreated, the connective tissue will eventually slowly fill the defect [3]. Such wounds are prone to problems like infection and have a sluggish healing rate. Patients with co-morbidities that are hidden (such as diabetic ulcers or vascular pressure ulcers) or
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
those who have post-surgical wound dehiscence frequently have this form of wound healing (often because of infection, hematoma, or mechanical tension). The wound remains open until any infection or contamination involving non-viable tissue is addressed. At this point, the wound's edges are brought together, and the healing process proceeds as planned. This method of healing is known as "delayed primary intention" or tertiary intention [4]. Clinically, depending on how rapidly they heal, wounds are categorized as either chronic or acute. Acute wounds are ones whose healing times typically fall between 5 and 10 days, or within 30 days, and chronic wounds are those that do not heal properly and progresses through the regular stages and cannot be resolved promptly and systematically. Today, there is much more to understanding wound healing than merely expressing that there are three stages: maturation, proliferation and inflammation. Wound healing involves complex chain reactions and interactions between cells and "mediators." New mediators are identified every year, and our knowledge of cellular interactions and inflammatory mediators' advances. A substantial sector offers healthcare professionals an extensive and intricate set of tools to tackle challenges in wound healing. Numerous internal and external factors have an impact on wound healing [5].
Wound healing management
1.Common approach
1.1. Infected wound treatment
Bacteria are more prevalent near chronic wounds, although they don't affect treatment. However, increasing the bacterial burden disrupts wound healing and causes infection [6]. An illness that has spread to other tissues may become worse and develop into a systemic infection. Infection can cause a delay in treatment, increased foul-smelling discharge, increased discomfort, increased wound size, and unstable tissue. Topical cleansers and antimicrobials used to treat local wound infections can hasten to heal. Cleaning wounds can be done with water or a regular saline solution but detergent should not be used because of tissue damage and toxicity properties. However, cleaning wounds with diluted vinegar or acetic acid (0.5%) has significant antibacterial properties. According to one study, disinfecting a wound by immersing it in 0.5 percent acetic acid for 10 minutes kills both gram-positive and gram-negative germs [7]. Systemic microorganisms that eventually acquire resistance to systemic medication as a result of their direct targeting of bacterial loads, and topical antimicrobials are favoured for superficial wounds. However, it has been shown that topical treatments can sometimes cause bacterial resistance; as a result, they should be discontinued following therapy. Additionally, it should be emphasized that using certain of these antibiotics repeatedly, such as gentamicin and neomycin in open wounds for extended periods of time, which should be avoided because it could cause contact dermatitis [8].
1.1.2. Debridement of wounds
An accurate examination of the wound and the patient is the first step in successful wound treatment. This procedure starts with the identification of the cause of the wound and ends with the improvement of the patient's health [9]. The elimination of damaged tissue is a crucial step in wound healing. Ulcers' necrotic tissue can halt treatment and stop keratinocytes from moving to the wound bed. The techniques for debridement include surgical, mechanical, enzymatic, and biological processes [10]. Debridement of wounds, particularly those in the lower region of the leg, requires a vascular examination. Except for patients with peripheral neuropathy, surgery can be performed using specialized tools under local or general anesthesia. Surgery's damage to both damaged and healthy tissue, though, is one of its drawbacks [11].
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" 25-26 SEPTEMBER, 2024
1.2. Wound dressing
Choosing the appropriate dressing to absorb the discharge is necessary for moisture balance. There are various forms of wound dressing, ranging from straightforward ones like over-the-counter bandages to sophisticated ones like designed dressing with stem cells. Clinical trials frequently use moisture-retentive dressings (MRD), especially for chronic wounds, and their advantages have been established. One benefit of these dressings for chronic wounds is that they are cost-effective in terms of care [12]. There are five different forms of MRD: Films Usually formed of a clear, thin sheet of polyurethane, films can be attached to the skin using acrylic. For severe surgical wounds, the films are also helpful [13]. The interior layer of foam, however, is constructed of a hydrophilic substance to prevent bacterial contamination, while the outer layer is built of a hydrophobic polyurethane. These bandages are suitable for minor to common wounds [14]. Coverings known as hydrocolloids are made of polyurethane foam or film that adhere to a matrix of gelatine, pectin, or carboxymethylcellulose [15]. A yellow gel is created when hydrocolloid and wound fluid combine. These bandages are beneficial for wounds with a moderate level of discharge. Due to its waterproof nature, Additionally, you can use this dressing when bathing or swimming, but its edges may get sore. Usually, every 2-4 days, this dressing is replaced [16]. Alginates these dressings are highly absorbent and are made from cellulose polysaccharides produced from kelp, a form of seaweed, or algae. Alginate dressings' ability to absorb moisture is due to the calcium and sodium exchange process, which also provides them a haemostatic property. They are made of soft sheets that absorb wound fluids. Alginates should only be used for lesions that are highly secretive and are not dry or less secretive. Hydrogels are hydrophilic polymer networks that resemble liquid gels. They may be applied to the wound surface as sheets. In comparison to alginate, the most frequent application of hydrogels is to treat necrotic, dry wounds, which helps patients who are suffering from painful wounds [17].
2.Advanced approaches to wound healing management
2.1. Hyperbaric oxygen therapy
In hyperbaric oxygen therapy, patients may receive 100 percent oxygen at higher pressures than atmospheric pressure or at sea level. Only the cost-effectiveness and general benefits of this treatment have been determined with any degree of certainty. However, higher oxygen has been shown to enhance angiogenesis and improve fibroblast and leukocyte function [18]. The use of this treatment procedure is quite restricted due to the fact that there are still issues in the field and the need to take into account the facilities that are available. For diabetic patients, particularly those with foot ulcers, this treatment can be a very beneficial addition to regular wound care. In a study, diabetic individuals with foot sores received hypertensive oxygen therapy instead of usual care [18].
2.2. Wound healing by Negative pressure
Another technique for healing wounds is negative pressure. By creating a controlled, long-lasting vacuum, negative pressure enhances wound healing. reduction of unnecessary discharge Negative pressure, enhanced blood flow, and wound shrinkage are all required for wound healing [19]. In this operation, a tube-connected sponge with a microprocessor-controlled pump is introduced into the wound. So, sustained, regulated pressure creates the environment for quick wound healing. This technique can be used to treat a variety of wound types, including surgical, wounds acute wounds, and chronic wounds. This feature expedites the rehabilitation process for patients [20].
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" 25-26 SEPTEMBER, 2024
2.3. Layering materials for dressing
Utilizing various material qualities to create multilayer dressings is another novel approach to wound healing. A semi-adhesive layer or non-adhesive layer of highly absorbent fibers, such as cotton, rayon fabric, and other compounds, is used to make up absorbing dressings in the medical field. The dressing contains Nonwoven polyester fibers are used in the layer that comes into contact with the wound, nonwoven bamboo fibers are used in the absorbent layer, and nonwoven 6/PCL nylon is used in the top layer. created a sheet of fibers by combining an alginate and a hydrofiber layer. These layers merge with an extra viscous outer layer and adhere to a layer of activated carbon. Another illustration of a multilayer dressing is one made of alginates and hydrocolloids, which are particularly useful for treating pressure sores, burns, and superficial foot wounds [21].
A recent study explored the best ways to treat chronic wounds by combining the components of multilayer wound dressings with combination medications. This study's objective was to create a multilayer wound dressing using two different pharmacodynamic medication combinations [22]. The first layer includes. Lidocaine was efficient for fast pain reduction and instant release, the second layer is alginate which includes diclofenac, and the final layer of viscose provided long-lasting pain alleviation [23].
► c
Fig.1.Multilayer wound dressing, in this figure layer A consist of Lidocaine, layer B is of alginate and consist of diclofenac and layer C consists of viscose.
2.4. New methods of debridement
The use of larvae is an entirely different technique for treating wounds. Larvae (Greenflies Lucilia sericata) have positive benefits on a persistent, unhealable injury. These qualities include wound active strengthening of granulation tissue synthesis, disinfection, and debridement of necrotic tissue. The interactions between the two have a big impact on how new tissue grows [24]. A cage containing sterile larvae is covered with a wound dressing. The larvae often hang out in the dressing area for 24 to 60 hours before getting a saline solution wash. New sterile larvae carry out this process again if necessary. When surgical methods are not an option, collagenase ointment (250 units per gram), obtained from the bacterium Clostridium histolyticum, is particularly efficient for dry wounds with fibrin debris and no granulation tissue. Endothelial cells and keratinocyte migration are accelerated by collagenase. for removing necrotic debris from partial-thickness wounds, pressure ulcers, and foot ulcers, enzyme destroyers are a useful choice. A quick
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
and effective debridement technique frequently used for fibrinous wounds is biological debridement, which uses medical maggots. Because of the patient and provider's discomfort and the high level of pain, this approach is frequently underutilized. According to a recent randomized controlled experiment, participants who received larval treatment felt higher discomfort than those who received hydrogel dressings [25].
2.5. Nanomedicine for treating wounds
Numerous disorders, including cardiovascular disease, cancer, diabetes, tissue engineering, inflammatory diseases, regenerative medicine, and wound healing, have benefited from breakthroughs in nanomedicine in terms of diagnosis and treatment. Nanoparticles are utilised to reduce inflammation, manage microbial infections, and promote the healing of wounds because of their distinct physical, chemical, and biological characteristics. Due to their ability to mimic the extracellular matrix (ECM) structure, enhance wound respiration and greater porosity, absorb wound secretions, and ability to alter several cellular and molecular pathways to release ions or create reactive oxygen species (ROS), Nanoparticle-based dressings hasten the healing of wounds [26].
2.6. Growth-factor transmission via nanoparticles
Skin wound healing involves several steps, an intricate process that is controlled by a signaling network made up of cytokines, chemokines, and growth factors. Growth factors are secretory, soluble proteins with the capacity to influence numerous crucial cellular procedures for tissue regeneration. Growth factors and peptides can now be transferred using improved delivery technologies and biomaterial carriers like nanoparticles and nanofibers EGF is used as a common growth factor to heal skin ulcers. Besides, succinylated dextrin is employed to transport and release EGF. The FGF2 stable delivery method is yet another novel approach to promoting wound healing using heparin-conjugated fibrin. Comparatively to the control group, Endothelial cell proliferation is boosted by the bFGF-dual emulsion-loaded fibrin hydrogel carrier system. In a different experiment, epidermal growth factor bound to heparin was administered to injured mice, and after 7 days, the wound's proliferation and regeneration were maintained while keratinocyte migration increased [27].
2.7. Utilizing electrical components to ramp up wound healing
The US National Aeronautics and Space Administration (NASA) recently released a new electrically active material for wound healing that is dependent on polyvinylidene fluoride. This device employs electrical activity to shield the wound and simultaneously expedite the healing procedure [28]. The bandage is constructed of an electrical substance (polyvinylidene fluoride, a thermoplastic fluoropolymer that becomes extremely piezoelectric when polarised), which stimulates cell growth via pressure and body heat without the need for supplementary external energy input. These materials offer significant benefits, including the improvement of the wound healing process and a range of simultaneous activities supporting both wound healing and protection. [29].
2.8. Photonics
Based on the fact that photonics has made significant advancements in the medical field, the limitation on penetration depth makes it difficult to use photonics in clinical settings. Implantable light delivery systems with the ability to transmit light have been developed to get around these problems. Because they are biodegradable and biocompatible, these tools are nontoxic and absorbed by the tissue. Good results have been obtained using the treatment method in
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
an in vivo experiment to heal cuts on pig skin's outer surface. In the phase of wound healing, the potential for hydrogen (pH) evaluation is a significant signal. This is the first time, a smart wound dressing incorporating fiber optics was utilized to measure pH in a study in 2021. In this study, rhodamine B dye was applied to pH-sensitive intrinsic fiber optics using polydimethylsiloxane (PDMS) precursor before the fiber was embedded in a hydrocolloid dressing [30].
Conclusion: This review extensively examines the forefront of contemporary methodologies in the field of wound healing, shedding light on the latest and most advanced approaches, highlighting the challenges posed by factors such as antibiotic resistance arising from biofilm formation, the expedited degradation of biological therapeutics like growth factors within the persistent milieu of chronic wounds, and the suboptimal drug bioavailability inherent in medicated wound dressings. Addressing these impediments necessitates a paradigm shift, and nanotechnology, alongside gas plasma-based strategies, emerges as a promising framework to surmount these limitations. Optimal wound healing, characterized by a well-coordinated process, is contingent upon the individual's robust nutritional status, hemodynamic health, and biochemical stability. Nonetheless, the reality often presents a scenario where patients undergoing secondary intention wound healing harbor complicating factors, most commonly malnutrition, warranting careful consideration and targeted intervention by healthcare professionals. Recognizing the intricacies of the procedures and elements integral to normal wound healing is imperative for clinicians. Throughout healing phases, a myriad of factors, either individually or synergistically, can impact the ultimate result of the healing procedure. This nuanced understanding underscores the complexity inherent in guiding patients through the intricacies of wound healing, thereby enhancing clinical outcomes.
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