**Abstract**

Worldwide, cutaneous lesions care represents a daily challenge for the medical system, with an increasing prevalence from year to year (from ~5 million in 2005 to about 8 million in 2018) and high costs for their treatment (between ~\$28 billion and ~\$97 billion). Injuries are the most frequent and destructive form of skin damage, affecting patients' quality of life. To promote wound healing, an ideal treatment involves proper dressings that can manage the local pain, inflammation, or infection. Passive or dry traditional dressings, such as cotton, gauze, or lint, have limited therapeutic actions and demand periodic replacement of the dressing. Therefore, an optimal alternative for advanced wound care is represented by hydrogels, one of the five classes of modern dressings, which assure excellent local moisture, due to their high ability to absorb a large volume of water inside their three-dimensional networks. Moreover, hydrogels possess suitable biocompatibility, biodegradability, porosity, elasticity, flexibility, and biological properties similar to the extracellular matrix. This chapter presents the main characteristics of the hydrogels and the recent research regarding the development of new hydrogel dressings, based on natural, semi-synthetic, or synthetic biopolymers, loaded with varied therapeutic agents to stimulate the tissue regeneration of different etiologies cutaneous lesions.

**Keywords:** different etiologies wounds, hydrogel dressings, wound healing, wound management, tissue regeneration, therapeutic agents sustained release

### **1. Introduction**

With a length of ~2 m<sup>2</sup> and weight of ~15% of the body mass, the skin represents a sophisticated tissues complex of the human body, being the largest and the heaviest organ [1]. Due to its optimal physicochemical characteristics, the skin is a dynamic and effective outermost barrier, defending the body against the external surroundings [2]. In addition to the role of physical protection, the skin is involved in the regulation of the body's homeostasis, synthesis of vitamin D [3], and control of the temperature

and blood pressure. Furthermore, it impedes dehydration, maintains an optimal level of moisture and body nutrients, and exhibits self-healing properties [4]. Skin is also an essential sensory organ when it connects with the environment, and the stimulation is perceived on the human body as pain, temperature, and pressure [5]. Normal skin represents a stratified epithelium that is composed of three principal layers: epidermis, dermis, and subcutaneous tissue. The epidermis is made up of many cells, including melanocytes, Merkel, and Langerhans cells, but keratinocytes are the most numerous (~95%). This stratum has a thickness of 0.05–0.1 mm, and it does not contain blood vessels and sensory nerve endings [6]. Dermis represents a hard fibrous layer, due to its composition in collagen and elastic tissues. It is based on a supporting network that furnishes elasticity and toughness to the skin. Dermis exhibits a noticeable ability to absorb the water. Its thickness varies from 0.5 mm to 5 mm or more according to the skin region. Compared to the epidermis, the dermis is vascularized [7]. Hypodermis (subcutaneous tissue) represents the profound stratum of the skin, and it is made of fat cells among which are found elastin fibers, collagen, nerves, lymphatic, and blood vessels. The main roles of this layer are to store energy, to thermally insulate the body, and to defend against physical trauma [8].

Being the main organ that interacts directly with the environment, the skin is principally disturbed by external agents, such as chemicals, microorganisms, UV and electromagnetic radiations, allergens, heat, pollution, and mechanical trauma [9]. On the other hand, the skin can also suffer various modifications due to behavioral factors (smoking, alcohol, and nutrition), physiological factors (obesity), demographic factors (age and gender), and pathological factors (numerous local and systemic diseases) [10, 11]. All these mentioned factors often generate a skin injury and a delay in the healing process, so the restoration of healthy and functional skin is still a big challenge for the medical community [12] and an increasing problem worldwide [13]. Depending on the degree of the skin damage, cutaneous lesions can necessitate a long-term treatment, which involves a huge financial cost for global healthcare systems [14]. Statistics showed that the number of people with skin injuries of different etiologies worldwide is constantly growing from ~5 million in 2005, ~6 million in 2015 to about 8 million in 2018, and the total costs for their medical care are estimated to be between ~\$28 billion and ~ \$97 billion. Taking into account the dynamics of the factors that cause damage to the skin tissue, in the coming years, the total costs for their treatment are expected to rise [15, 16]. From all types of wounds, chronic lesions have the highest incidence in the population. Thus, in developed countries, approximately 1–2% of people will suffer a chronic lesion during their lifetime [17]. The highest increase is in the case of injuries caused by diabetes because it is estimated that in 2025 there will be at least 400 million people with diabetes globally, most cases being in South Africa, Asia, and Africa. About 15–25% of these people will develop throughout their life one of the major complications of diabetes which is the diabetic foot ulcer [18].

Most often a wound is accompanied by pain that can vary from mild to severe depending on the degree of the skin impairment. Hence, the personal life quality of the patients is considerably affected because they have to limit their daily activities, which negatively influences their physical, psychological, and social conditions [19, 20].

Optimal wound management needs physicians to comprehend the etiology of the wound, its healing time and complexity, the mechanism of injury healing, and the factors which affect the skin regeneration to make the right decision regarding the most efficient treatment for a proper cutaneous tissue restoration [21]. Since ancient

#### *Promising Hydrogels-Based Dressings for Optimal Treatment of Cutaneous Lesions DOI: http://dx.doi.org/10.5772/intechopen.105825*

times, the care of a lesion involves its cleaning and applying a patch (traditional dressing) that allows protection from the external environment, but it cannot absorb high amount of exudates and requires regular application that produces soreness when changing the patch; moreover, the common patch owns modest adhesive characteristics and cannot furnish an adequate drainage for the injury. Consequently, the wound healing process is delayed, and the quality of the patient's life is seriously affected [22]. Nowadays, those patches have been switched with new wound dressings (modern dressings) that function as a physical and defensive barrier, swallowing the exudate and facilitating the healing process [23]. Over the last few years, modern dressings have been developed, which include hydrogels, hydrocolloids, semi-permeable films, foams, and alginates [24]. Comparing to the traditional dressings, these modern wound dressings, due to their improved structure, have a high capacity to generate a moist environment all over the skin lesion and to keep it, promoting the healing process and the reepithelialization by developing the proliferation of fibroblasts and enhancing the synthesis of collagen [25]. Moreover, they are semi-permeable and highly absorbent dressings and semi-occlusive or occlusive that stimulate the granulation tissue production and promote the epithelial cells movement from the injury margins to its center, providing an enlarged functionality [22].

Thus, this chapter highlights the main structural and functional properties of hydrogels, which are hydrophilic macromolecular networks, formed by crosslinking of diverse polymers, physically or chemically [26]. Also, this chapter presents recent studies regarding the broad applicability of hydrogels as bioactive dressings, which, after application to the wound bed and alleviate the pain, inflammation, and infection that generally follow a lesion [27]. Primary results consist of anatomical, functional, and esthetic restoration of the skin, improving the patient's quality of life [28].

### **2. Complexity of cutaneous lesions and skin regeneration process**

Cutaneous lesions appear while the skin tissue is broken, or the cellular stability is imperiled under the action of physical, chemical, mechanical, and thermal agents or because of genetic diseases and metabolism-linked factors [29].

In the first instance, skin injuries can be clinically partitioned into acute and chronic injuries. Acute lesions are those wounds that often heal totally, with minimal scarring, in a period between 8 and 12 weeks [30]. Mainly, acute lesions can be produced by mechanical trauma; thus, these types of lesions can be classified inside one of these eight types: abrasions (it happens when a mechanical power scratches away a limited thickness of the skin) [31], avulsions (occurs when the primary layers of the skin are cut from the underlying fascia, for example, injury produced by animal bites) [32], contusions or bruises (fist leads to a contusion), crush wounds, cuts (knife or paper can cause a cut), fish hook injuries, incised wounds (it is the result of a surgical cut inside the skin) [33], and lacerations or tears (it means a break in the skin, which can be generated by a sharp object, for example, metal, glass, or wood) [34, 35]. Also, in the category of acute wounds are found burns and chemical lesions. On the other hand, chronic wounds heal slowly, their healing time exceeds 3 months, and they often reoccur. According to the Wound Healing Society, in this category of cutaneous lesions are included: pressure, venous, and arterial insufficiency, diabetic ulcers, and also malignant wounds [17].

Furthermore, from an etiological point of view, cutaneous lesions can be categorized as follows: surgical wound, which is a mechanical lesion produced by surgical

incisions, for example, to eliminate tumors [36]. Traumatic injury is an accidental and a spontaneous lesion that can vary from a small wound, such as a scraped knee, to a serious injury, such as a gunshot lesion. Abrasions, lacerations, skin tears, bites, burns, crush, and stab injury are some examples of traumatic wounds [37]. Radiation lesion is the result of radiotherapy and surgery, two treatment methods that are generally used for the therapy of cancerous tumors, lesions whose delayed healing produces physiological and psychological stress to the patient [38]. Chemical and thermal injuries (burns) are produced by a diversity of factors such as radiation exposure, electricity, corrosive chemicals, or thermal agents [39]. In these types of injuries, it is very important to know how deep the wounds are and how much of the body surface is affected, all these for good management that can lead to a decrease of wounds healing time [40]. According to World Health Organization, there are reported globally every year more than 11 million burn wounds and their medical care passes \$12 billion per year [41]. A lesion becomes malignant when cancerous cells attack the epithelium, penetrate blood and lymph vessels, and invade the epidermis; mostly, this type of wound produces death and necrosis of the tissue [42]. Melanoma is metastatic skin cancer, with an increased risk of death, produced by uncontrolled growth of melanocytes that spread abnormally in neighboring tissues. This type of cancer produces severe wounds, requiring special treatment for optimum treatment [43]. Psoriasis is an autoimmune disease, characterized by erythematous-scaly lesions (crumbly white peels on irritated skin background) on the scalp, elbow, and knees, lesions to the face caused by sun exposure, and lesions at the level of the inguinal, axillary, or interfacial skin folds [44]. A pressure ulcer (pressure lesion, pressure sore, decubitus ulcer, or bedsore) is a surface of localized disturbance to the skin and hidden tissue, and it is induced by pressure, shear, or rubbing. The main risk factors that can lead to a pressure ulcer are incomplete nutrition, peripheral vascular disease [45], elderly people, obesity, diabetes, inadequate posture, pregnancy, smoking, or an increased frequency of infection (osteomyelitis) [46]. The most frequent complication of diabetes mellitus is diabetic foot ulcer, which affects 15–25% of diabetic patients. This is a condition that requires a long period for healing, or in some cases, it does not heal and can lead to infection, the major consequence being lower limb amputation [47, 48]. In close relation with diabetic foot ulcer is vascular ulcer, which is caused by disorders of the circulatory system; there are two principal types: venous ulcer (varicose ulcer) and arterial ulcer [49].

Based on contamination and postoperative infection risk, wounds can be classified in classes I, II, III, or IV. Class I or clean wound includes injuries that are infectionfree, although current bacteria on the skin contaminate the injury [50]. Class II or clean-contaminated wound involves injuries, which affect the respiratory and digestive system, characterized by no loss of tissue fluid [51]. Class III or contaminated wound contains non-purulent inflammation and class IV or dirty/infected wound contains purulent inflammation [52].

According to appearance and injured tissue coloration, a wound can present necrotic tissue (characterized by a black or olive green coloration, often at pressure ulcer) [53], sloughy tissue (characterized by yellow coloration, related with excess exudates, produced during the inflammatory stage) [54], granulation tissue (characterized by red or deep pink coloration, typical for proliferative phase) [55], epithelializing tissue (characterized by pink coloration and formation of a new epidermis; it develops in migratory and proliferative phases) [56], and infected (malodorous) tissue (characterized by red coloration, hot inflamed tissue, pus formation, and unpleasant odor) [57].

#### *Promising Hydrogels-Based Dressings for Optimal Treatment of Cutaneous Lesions DOI: http://dx.doi.org/10.5772/intechopen.105825*

An injury is classified according to complexity in simple and complex (complicated). A simple wound affects the skin tissue without any complication. On the other hand, a complex wound leads to a major tissue loss and a complicated wound involves an infected complex wound [58, 59].

Conforming to the depth of injury or number of skin layers affected, a wound can be superficial, partial thickness, or deep dermal and full thickness. A superficial wound is characterized by affecting only the epidermal skin surface, with minimum scars and a short period for healing, less than 10 days [60, 61]. A partial thickness or deep dermal wound represents a type of injury that affects the epidermis and also the inner dermal layers, containing blood vessels, sweat glands, and hair follicles; it requires between 10 and 21 days for healing, with the formation of scar and reepithelialization [62, 63]. A full thickness wound appears when hypodermis and also epidermal and dermal layers are damaged and the healing time is longer than the other two types of wounds (more than 21 days) [64, 65].

The regeneration of cutaneous lesions represents a fundamental physiological process that consists of a succession of cellular and biochemical events, which begin when a skin lesion occurs in order to reestablish the impaired tissue. The wound healing process involves more consecutive stages, but which still overlap: hemostasis, inflammation, proliferation, reepithelialization, and remodeling; therefore, skin tissue repair is one of the most complex processes that occur in the human body [66].

Multiple factors can delay the wound healing process, such as: different underlying physiological diseases (diabetes mellitus, human immunodeficiency virus, tumor resection, after organ transplantation, inborn genetic immunodeficiencies, burns, hypoxia, and vascular and autoimmune disease or cancer), obesity, continuous infection, stress, elderly population, sex hormones, gender, smoking, and malnutrition [67, 68]. Another cause for this delayed wound healing and epithelialization is represented by high levels of proteolytic enzymes and cytokines [69]. These factors lead to the production of a substantial amount of exudate [70], which decreases the mobility of lymphocytes and produces maceration of healthy tissue around the injury, the major problem which results being the inhibition of the wound repair process [71].
