Antimicrobial Dressings: The Wound Care Applications

Antimicrobial Dressings: The Wound Care Applications explores the literature surrounding the catalytic behavior of proteolytic enzymes immobilized together with nanoparticles. As numerous applications using proteolytic enzymes for debridement, silver as antibiotic and nanoparticles for enzyme immobilization were developed in the last years, this book explores interdisciplinary information combining nanotechnology, biotechnology and medicine and how it's still in early stages. The book adopts a holistic approach in a lifecycle context to evaluate their final feasibility, including industrial exploitability without disregard of the potential risks of enzymes and nanomaterials to human health and the environment.

• Describes the drawback of using unstable enzymes in wound debridement such as infections, irritations, low availability, rapid elimination from the body, and impossibility of creating a high local concentration of the preparation without increasing its systemic concentration
• Provides information on higher efficient antimicrobial property and enzyme stability using nanoparticles as carriers for enzyme immobilization due to minimum diffusional limitation, maximum surface area per unit mass, and high enzyme loading
• Discusses the physical characteristics of the nanoparticles through multilayer polyelectrolytes encasing, such as diffusion and particle mobility that will influence the catalytic activity, pH and thermal stability of attached enzymes

• Language: English
• Publisher: Academic Press
• Release date: Feb 10, 2023
• ISBN: 9780323950756

Book preview

Chapter 1

Overview and summary of antimicrobial wound dressings and its biomedical applications

Tarun Kumar Kumawat¹,², Varsha Kumawat³, Vishnu Sharma², Anjali Pandit², Bhoomika Sharma², Sagnik Nag⁴, Nalinee Kumari⁵ and Manish Biyani⁶,    ¹Department of Botany, University of Rajasthan, Jaipur, Rajasthan, India,    ²Department of Biotechnology, Biyani Girls College, Jaipur, Rajasthan, India,    ³Biyani Institute of Pharmaceutical Sciences, Jaipur, Rajasthan, India,    ⁴Department of Biotechnology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India,    ⁵Department of Zoology, DPG Degree College, Gurugram, Haryana, India,    ⁶Department of Bioscience and Biotechnology, Japan Advanced Institute of Science and Technology, Nomi, Ishikawa, Japan

Abstract

Wound healing is accomplished through a number of molecular processes that improve tissue integrity and cell metabolism. Wounds infected with biofilm are difficult to treat, both acutely and chronically. The interactions of antimicrobial dressings with microbial contamination, biofilm substrate, and the general protein-rich wound milieu remain unknown. In most cases, wounds are infected, and infection is a problem because it causes inflammatory responses, which prolongs the healing process. As a result, there has been a surge in interest and effort in avoiding and effectively resolving wound infections through the use of antimicrobial drugs, either alone or in combination with medicated dressings. Various antimicrobial compounds have been added to the dressings’ structure to improve their antibacterial properties. Honey and essential oils are antimicrobials, as are antibiotics (such as tetracycline and ciprofloxacin) and nanoparticles (e.g., silver nanoparticles). When administered systemically, they have the advantage of overcoming obstacles such as circulation issues and requiring lower doses than oral or intravenous administration. This chapter will examine several antimicrobial agents used to treat infected wounds, as well as their mode of administration and biomedical applications.

Keywords

Antimicrobial wound dressing; antibiotics; nanoparticles; natural; wound healing

List of abbreviations

AgNPs silver nanoparticles

AuNPs gold nanoparticles

CS chitosan

ECDC European Centre for Disease Prevention and Control

ECM extracellular matrix molecules

EO essential oils

EPS extracellular polymeric substances

IV intravenous

MRSA methicillin-resistant Staphylococcus aureus

PHMB polyhexamethylene biguanide

PVPI povidone iodine

ROS reactive oxygen species

TTC tetracycline

1.1 Introduction

The skin accounts for approximately 15% of total body mass and is composed of three layers: epidermis, dermis, and hypodermis [1]. The skin senses temperature and moisture to govern the body’s interior environment [2]. The most important functions are preventing desiccation and protecting internal organs and other structural components from environmental damage [3]. Burns, stitches, and accidental cuts cause the most damage to the skin [4]. Every day, a wide range of surgical operations are performed all over the world. The majority of these treatments leave some kind of wound that must be treated in order to prevent further health problems [5]. A wound is defined as any change in the structural or functional characteristics of the skin [6]. Many different factors can be used to classify a wound, including its origin, location, symptoms, severity, and amount of tissue lost. It can also be classified as clean, polluted, diseased, or colonized [7]. Wounds can be acute or chronic in nature. A chronic wound has impaired physiology, whereas an acute wound has normal physiology and healing stages [8].

When microbes enter a skin breach, they cause wound contamination. Infection slows wound healing and may result in death. Life-threatening wounds can be fatal both immediately and later. The former is caused by severe exsanguinations or underlying organ damage, whereas the latter by infection and sepsis. As a result, the primary issue with wound care is wound infection [9]. The most invasive infections in burn wounds worldwide are caused by Methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus (MRSA). Pseudomonas aeruginosa and multidrug-resistant Acinetobacter baumanii infections are more common in tropical climates [10]. As a result, wound care that aims to reduce bacterial infection has received a lot of attention around the world. Dressings have been used to cover wounds for a long time because they aid in wound healing by acting as a physical barrier against infection, keeping the surrounding area moist, and absorbing any exudates. The following are the requirements that an optimal wound dressing should meet:

1. absorb and eradicate the toxins and exudate,

2. permit gaseous exchange,

3. maintain a high moistness,

4. prevent secondary infection,

5. provide thermal insulation,

6. not be cytotoxic [11].

Wound healing continues to be the most difficult problem in wound therapy [12]. It is widely accepted that providing a moist, warm environment for a wound by covering it with an optimal dressing membrane is an effective way to promote healing. This environment also encourages the growth and colonization of microorganisms that require sophisticated medical treatments. Antimicrobial wound dressings reduce bacterial biofilm formation and the spread of microbial infestations [13,14]. The healthcare industry’s focus on wound care has shifted globally in order to provide a more supportive environment for healing [15]. Wound infections were often difficult to treat, but patients now have access to wound dressings containing silver, iodine, polyhexamethylene biguanide, and octinidine [16]. The alarming global development of multidrug-resistant bacteria, driven by antibiotic abuse and misuse, is also increasing the need in the wound care industry for sophisticated antimicrobial chemicals and wound dressings with a broad spectrum of action [17]. These dressings deliver antimicrobials in a controlled manner, achieving antibacterial action while maintaining therapeutic concentrations in healing tissues [18].

1.2 Pathophysiology of wound and healing process

Wounds form when the cellular cohesion of tissue is disrupted by structural, physiological, or metabolic disorders [19]. Skin wounds are characterized as either acute or chronic based on their healing duration [20,21]. Acute wounds are defined by a disruption of tissue integrity that occurs suddenly, recovers quickly, and has no long-term consequences [22]. Platelets, keratinocytes, immunological surveillance cells, and fibroblasts are among the cell types involved in tissue repair [23]. The dermal and epidermal integrity is compromised, resulting in chronic wounds that do not heal in a reasonable amount of time and are linked to predisposing factors [24]. Bacterial colonization is common in chronic wounds and is thought to be a primary source of inflammation [23]. The majority of chronic wound patients, such as the elderly and diabetic patients with lower body (leg and foot) ulcers, have poor blood circulation in their lower limbs, rendering conventional oral and intravenous (IV) antibiotics ineffective [21].

In a series of perfectly synchronized processes, the wound healing process involves both local and mobile cells, as well as extracellular matrix elements and hydrophilic mediators [6]. Hemostasis, inflammation, migration, proliferation, and finally remodeling are the stages of skin wound healing [21,25–28] (Fig. 1.1). The production of fluids, proteins, and dead cells by metabolically active damaged tissue in the early stages of wound healing reduces the risk of bacterial infection [29]. It is critical to create a controlled environment in the wound area, such as aeration, temperature, and the availability of trace elements, vitamins, and minerals, in order to promote complex cellular activity during the recovery process [30,31].

Figure 1.1 Classification of dressings for wounds.

1.3 Wound dressings

Every year, thousands of people are burned by hot water, fires, accidents, and boiling oil. Such mishaps frequently result in disabilities during therapy, excessive medical costs, and even death. Keeping wounds clean and moist while preventing bacterial and fungal infections are difficult aspects of wound care management [9]. Skin wound management focuses on fast and effective healing. This goal can be achieved by dressing the wound. The wound dressing is a critical component and clinical protocol of care for the healing process [32] which have an essential function to play in the control of exudate, as well as infections [33]. Wound dressing materials have a variety of applications. As a result, wound dressings are classified into four types based on their interaction with biological tissue: dressings that are traditional or passive, skin substitutes, artificial or interactive dressings, and bioactive dressing [34–37] (Fig. 1.2).

Figure 1.2 The healing procedure for a wound.

From 2200 BC, one of the earliest medical journals describes wound healing as three therapeutic gestures: washing, plastering, and bandaging. Although wound healing technology appears to be unchanged, it has advanced [38]. Wound dressing and healing research was largely ignored until the mid-1960s. It was previously assumed that keeping the wound dry and exposed aids in faster and more efficient healing [39,40]. The ideal conditions for wound healing were initially proven by Winter [41] using the first generation of polymeric materials used in wound dressings. This discovery has paved the way for wound dressing to go from inert to functionally active materials, radically altering how wounds are treated.

A wound dressing should facilitate self-healing and shield damaged skin from external pressures, dust, and pathogens [42]. Dressings should be cytocompatible, soft, flexible, mechanically robust, gas permeable, and able to handle wound exudates [43]. Chronic and nonhealing wounds have a significant societal and economic impact. When wounds become infected with bacteria, they heal more slowly or not at all. As a result, as the prevalence of chronic wounds rises, so does the demand for more sophisticated therapeutic wound care. Current wound dressings fall short of ideal criteria, necessitating research into new, more effective dressings [44]. The wound care industry has recently been aware of a rising need for cutting-edge antimicrobial wound dressings [18].

1.4 Ideal wound dressing requirements

The best wound dressing maintains wound moisture, allows oxygen to pass through, absorbs wound exudate, accelerates re-epithelialization for wound closure, and reduces healing time, pain, and infection [45]. Moist dressings have been shown to promote faster wound healing than dry dressings. This is because skin regeneration and repair can only occur in a moist environment; otherwise, eschars or inflammation will form. As a result, wet or moist dressings were deemed the best choice for skin repair and wound dressing. Furthermore, they contain a high percentage of water and are naturally permeable. Furthermore, oxygen must be allowed to permeate the dressing in order to nourish repairing cells [46].

In general, the best way to treat slow-healing wounds is with a dressing that meets certain requirements. These requirements are shown in Fig. 1.3:

1. a physical barrier to stop further harm and exposure;

2. a carrier for a bactericidal chemical to get rid of bacterial infections around the wound;

3. an elimination mechanism for metabolites;

4. a wound-healing environment conditioner [29].

Figure 1.3 Ideal wound dressing requirements.

Several different approaches may be used to provide the most effective skin wound dressings available.

1.5 Antimicrobial wound dressing

Antimicrobial dressings contain an antibacterial agent, a biocide that inhibits germ growth in a wound or on clear skin. As technology has advanced, several antiseptic treatments that are far more effective at killing bacteria without harming surrounding healthy tissue have been developed. Antiseptics include silver, titanium oxide, zinc oxide, and iodine. Antimicrobial antiseptic dressings have proven effective in preventing microbiological infections. Antibiotic resistance in bacteria is the leading cause of the need for antimicrobial dressings [47,48]. The primary types of wound dressings that retain moisture, include films, sponges, foams, hydrocolloids, alginates, and hydrogels (Fig. 1.4; Table 1.1).

Figure 1.4 Wound dressing type.

Table 1.1

The ideal antimicrobial dressing must have a broad range of antimicrobial action against any pathogens responsible, be non-allergenic and non-toxic to the host, remove waste and maintain a humid environment in the wound area, release medications quickly and consistently, eliminate odor, and be reasonably priced [60,61]. The two most common types of antimicrobial wound dressing are antiseptic dressing and antibiotic dressing. Antiseptic dressings have numerous applications, including infection prevention and treatment caused by bacteria, fungi, protozoa, viruses, and prions [62]. Certain antiseptic dressings, on the other hand, cause cytotoxicity in host cells based on the number of doses, such as keratinocytes, fibroblast cells, and white corpuscles [63,64]. Fibroblasts and keratinocytes are highly intoxicated by povidone-iodine concentrations larger than 0.05% and 0.004%, respectively [65]. Antibiotic dressings are harmless and can successfully treat target locations while causing no harm to the host [64].

1.6 Antimicrobial agents for wound dressing

Wound dressings are meant to prevent and/or control infection in the wound and surrounding areas. To meet these expectations, researchers have created wound dressings that use antibacterial agents in a variety of ways. Antimicrobials should be effective against a wide range of infections while causing minimal toxicity or sensitivities [66]. A high bioburden will impair normal wound healing and may result in the formation of nonhealing wounds. Consequently, antimicrobial-containing dressings are frequently employed [67]. Natural products, antibiotics, and nanoparticles are used nowadays as antimicrobial agents.

1.6.1 Natural products for wound dressing

Because they are safer, naturally derived antimicrobials are becoming more popular in antimicrobial dressings. Biochemically produced bacteriocins, plant extracts, and enzymes are used in the antimicrobial dressing [68]. Dressings are now made from a wide range of polymers, both synthetic and natural. Poly (methacrylates), polyvinyl pyrrolidine, and other synthetic dressings are examples. These dressings are difficult to handle due to their low mechanical strength. As a result, considerable effort has been expended in developing dressings based on natural polymers [21]. Essential oil (EO), honey, and turmeric are used as natural products for wound dressing.

1.6.1.1 Essential oil dressing

Dressing with EO is high in bioactive components that have anti-allergic, antioxidant, antiviral, antibacterial, and rejuvenating properties [69]. Bioactive wound dressings with slow-release EOs keep wounds moist. This creates an ideal environment for wound healing [70]. Environmental factors such as the latitude at which plants are grown, the stage of growth at which they were selected, the drying techniques used, and the conditions under which they were stored all have an impact on the EO content. As a result, it appears that using pure chemicals found in EO composition is reasonable [71]. Antimicrobial properties of herbal EOs have been known for millennia. When it comes to antimicrobial composites, they have a lot more potential, particularly in terms of resistance to bacterial strains [72]. Many EOs, including thyme, peppermint, cinnamon, rosemary, tea tree, eucalyptus, lavender, and lemongrass, have antibacterial properties. Wound antibacterial properties of eugenol and limonene deposited in nanofluid-based magnetit [73]. Fermentation, expression, and solvent extraction are all common processes. Because of their extraordinary benefits, they have piqued the interest of many industries, including food, perfume, aromatherapy, and pharmaceuticals [74]. The health industry is becoming more accepting of plant EOs and their components due to their antioxidant and antibacterial properties [75]. It is a recent development to incorporate EOs into electrospun fibers for wound dressings [76].

1.6.1.2 Honey dressing

Honey is a naturally existing sweetener and is effective as a topical wound care treatment due to its broad-spectrum antibacterial action as well as its healing effects [77–79]. It can be stored for a long time and is easily assimilated even after a significant amount of time, making it an excellent choice for antimicrobial therapy due to the lack of toxicity or adverse effects, as well as the low cost of maintenance and easy availability [80]. According to studies, honey’s bioactivities boost the immune system’s response, reduce inflammation, and promote rapid autolytic debridement [79]. Despite being acidic, honey may provide the best environment for fibroblasts to function, making bacterial survival more difficult. For partial thickness burns and pressure ulcers, it outperforms amniotic membrane, silver sulfadiazine, and ethoxy-diamino-acridine with nitrofurazone [81]. Honey’s high osmolarity causes water to be evacuated from the wound when applied topically, diluting the honey and stimulating the glucose-oxidase enzyme. It forms a protective layer over the wound, keeping it moist and promoting wound healing [82]. It was reused for wound care and as a wound-prevention dressing [78]. Honey promotes collagen production and angiogenesis, which aids in wound granulation and epithelialization after debridement. The sugar, amino acids, vitamins, and minerals in honey may promote cell growth. The acidity of honey promotes the release of oxygen from hemoglobin into tissues [83]. Honey also contains enzymes such as catalase, which can aid in healing. Honey is used to treat burns, infected wounds, and decubitus ulcers. It is used to prevent bacterial colonization and to speed wound healing after vulvectomy. Gram-positive and Gram-negative bacteria and fungi are inhibited by honey [84].

1.6.2 Antibiotics and other antiseptics for wound dressing

Various studies have also shown that certain bacteriostatic or bactericidal medications can aid in the healing of wounds. Despite the fact that a wide range of antibiotics have been shown to be extremely effective against infection-causing bacteria, antibacterial wound dressings have only used tetracyclines (TTC), quinolones, cephalosporins, and aminoglycosides. Although several antibiotics are effective in treating wound infections, overuse and/or misuse of these medications may result in infection resistance [18]. Thousands of antibiotics exist, but only about 1% are currently in clinical use due to toxicity concerns or host cell absorption limitations. Antibiotics can interfere with bacterial function or structure, as well as metabolic processes [20]. The current crop of topical antibacterial agents is rounded out by antiseptics such as polyhexamine and silver compounds such as silver sulfadiazine and ionic silver-impregnated dressings [60].

1.6.2.1 Iodine dressing

Iodine has been used by doctors to keep wounds from becoming infected for nearly 150 years. Povidone-iodine has been used as a topical therapy since the 1950s [85]. Povidone iodine (PVPI) is a wound antiseptic. PVPI is a water-soluble combination of iodine and polyvinylpyrrolidone that kills bacteria, viruses, fungi, protozoa, and yeasts [86]. PVPI preparations have been accessible without a prescription in many countries for decades and are widely regarded as effective antiseptics [87]. Iodine’s primary function in wound treatment is as an antibacterial agent [88]. Iodine’s microbicidal effects include oxidizing nucleotides, fatty/amino acids, and respiratory chain enzymes, rendering them inert, and inhibiting bacterial cellular processes and structures [89]. In addition to promoting healing, antibacterial agents like cadexomer iodine have been proven to be effective against biofilm-forming P. aeruginosa and S. aureus [90,91].

1.6.2.2 Tetracycline dressing

Tetracycline (TTC) antibiotics are a class of antibiotic that are widely used in veterinary medicine, human medicine, and agriculture. These residues encourage the growth of antibiotic-resistant bacteria, which can be harmful to human health and increase disease risk [92]. These antibiotics can be applied topically to effectively destroy bacteria [93]. It is commonly used to treat skin infections such as acne, periodontal infections, and urinary tract infections. TTC was tested for antimicrobial activity against a variety of pathogens and was discovered to have a low minimum inhibitory concentration [94]. They are effective against Gram-positive and Gram-negative bacteria, have clinical safety, intravenous (IV) and oral forms, and are tolerated by the majority of group members. Their antibacterial properties, as well as the specificity of antimicrobial drugs, are influenced by their intrinsic antibiotic resistance pathways [95]. Despite their solubility in water, TTCs are highly miscible with alcohols, dimethyl sulfoxide, and dimethyl formamide. In polar solvents such as chloroform, dichloromethane, and ethyl acetate, all TTCs are very slightly soluble [96]. Currently, TTC-containing ointments are also utilized for treatment, which can cause skin sensitivity in rare cases. TTCs are broad-spectrum antibiotics having bacteriostatic properties. This antibiotic is sensitive to Streptococci, Listeria, pneumococci, Vibrio cholerae, Campylobacter jejuni, and Treponema pallidum, among other microorganisms. Interfering with protein synthesis in bacterial cells by inhibiting transfer-RNA binding to the m-RNA-ribosome complex is part of their antibacterial strategy. This prevents protein synthesis from taking place. TTCs are used locally in amounts ranging from 2% to 3%. Furthermore, it has the potential to cause photosensitization of the skin (pigmentation) [97].

1.6.2.3 Polyhexamethylene biguanide dressing

Polyhexamethylene biguanide (PHMB), also known as polyhexanide, has been around for a while and is commonly used as a preservative in pool sanitizers, contact lens solutions, and cosmetics. As a wound antibacterial, PHMB is available in solutions, gels, non-adherent bacterial barriers, and biocellulose dressings [98]. PHMB is an efficient, non-toxic antimicrobial agent with an antibacterial action against Gram-negative and Gram-positive bacteria [99]. It has demonstrated efficacy against a vast array of pathogens, including Escherichia coli, Staphylococcus epidermidis, and even Acanthamoeba castellanii [100]. The agent’s method of action is caused by the interaction between the positive PHMB group and the negative phospholipids in bacterial cell walls [101]. When applied to the skin, eyes, epithelium of the nose, or wounds, there have been no reports of PHMB causing any adverse effects. This substance is considered to be reasonably safe [102].

1.6.3 Nanoparticles for wound dressing

The discovery of new materials for wound dressings is a tough but necessary task [103]. Nanomedicine technologies, namely nanoparticles, are a viable strategy for the creation of potential antimicrobial medicines [104]. Recent consideration has been given to bioactive wound dressings that are activated by nanoparticles such as polymeric, silver, gold, glass, and zinc oxide to increase wound dressing potentials above traditional ones [105]. The incorporation of nanoparticles into scaffolds reflects the novel notion of nanoparticle dressing, which has recently received a lot of interest for wound healing [106].

1.6.3.1 Silver nanoparticles

Antibiotic-resistant bacteria have reignited interest in silver and other non-antibiotic therapies that had previously been abandoned following the discovery of penicillin and other antibiotics [107]. With the advent of nanotechnology, a new therapeutic modality for the use of AgNPs in wounds has emerged [108]. AgNPs have demonstrated significant promise in a wide range of applications, including detection and diagnosis, medication transport, biomaterials and device coating, novel antimicrobial agents, and regeneration materials [48]. Silver-based lotions, ointments, and AgNPs-based wound dressings are commercially accessible [109,110].

Silver ions kill bacteria through a variety of mechanisms, including binding to the outer membrane and the bacterial cell wall, which changes the permeability and, by extension, the function of the bacterial cell membrane. Silver metal and its compounds were thus able to prevent wound infection [111]. Burns, wounds, and bacterial illnesses are treated with metallic silver, silver nitrate, and silver sulfadiazine. Antibiotic resistance in bacteria and the discovery of antibiotic-resistant species have sparked interest in silver solutions for chronic wound treatment. Ionic silver is a powerful antibacterial agent whose use in medicine has increased as a result of antibiotic resistance [108]. AgNPs are antibacterial compounds that can be used to inhibit the growth of a wide range of microorganisms. AgNPs are thus useful in a wide range of medical devices and antimicrobial control systems [112]. In response to AgNPs, reactive oxygen species and free radicals were produced, which could lead to apoptosis-like reactions, cell membrane disintegration, and DNA damage. As is well known, the antibacterial activity of AgNPs varies greatly depending on their size, shape, and surface characteristics