**3. Bioactive hydrogel-based wound dressings**

Traditionally, wound dressings have to protect lesions from physical impairment and secondary infection, to ensure thermal isolation, to be comfortable, and to be quickly changed by a new dressing, without producing any trauma on the lesion site, facilitating the dermal regeneration, playing a passive role in the evolution of the wound healing process [72]. Presently, these functions are constantly evolving. Medical healthcare systems demand for new "intelligent" products, which function not only as a protective barrier but also strongly promote the skin repair process [73]. Over the last few decades, there were developed numerous modern (advanced) wound dressings to stimulate the regeneration of cutaneous lesions, such as semi-permeable films and foams, hydrocolloids, alginates, hydrofibers, and hydrogels. These advanced products for optimal clinical management of skin wounds represent, in 2019, about \$7.1 billion of the international market, and their manufacture is expected to increase to about \$12.5 billion in 2022 [74]. Of all these modern products, the most competitive candidate is represented by hydrogels.

**Figure 1.** *Molecular structure of hydrogel: (a) without bioactive agent, and (b) with bioactive agent.*

#### **3.1 Molecular structure of hydrogels**

Hydrogels, also known as aquagels, are a three-dimensional (3D) and crosslinked network of polymer chains, which can absorb massive quantities of water and body fluids due to their hydrophilic functional groups (hydroxyl, carboxyl, amide, and amino), adhering to the polymeric backbone [75]. The term "hydrogel" has been invented for the first time in 1894 by van Bemmelen. Due to their 3D structure, the molecular weight goes to infinity. The fundamental feature that characterizes the molecular structure of the hydrogel is the mesh size. There are two ways to crosslink the hydrogels: physically through hydrogen bonds and chemically through covalent bonds. The main property of the hydrogel is the super-absorbent capacity of water molecules that diffuse into the hydrogel network [76].

The molecular structure of hydrogel loaded or not with a bioactive agent is illustrated in **Figure 1**.

The swelling hydrogel includes three major phases:


The swelling ratio varies in accordance with polymers' content and the density of crosslinking [77].

#### **3.2 Classification of hydrogels**

Hydrogels products can be classified according to different measurable parameters as detailed below:


Regarding the network structure, hydrogels are mostly manufactured from crosslinking networks, so there are two major categories of hydrogels: physically and chemically crosslinked hydrogels. Physically crosslinked hydrogels have gained importance due to the fact that they are easy to produce because no crosslinking agents are used during the synthesis process; thus, these types of hydrogels are used in biomedical, pharmaceutical, and food industries. Many methods are used to generate physically crosslinked hydrogels: freeze-thawing, stereocomplex formation, ionic interaction, hydrogen bonding, maturation (heat-induced aggregation), noncovalent interaction, and thermoreversible gels [81]. Chemically crosslinked hydrogels present covalent bonds in the middle of the polymeric network that generate permanent hydrogels formation. These types of hydrogels are formed through reactions between functional groups of polymeric chains. Many methods are used to generate chemically crosslinked hydrogels: condensation reactions, polymer–polymer crosslinking, high energy irradiation, enzymatic reaction, grafting, and radical polymerization [82].

#### **3.3 Functional and technical properties of hydrogels**

Hydrogels are of huge interest for the development of new wound dressings due to their outstanding mechanical and biochemical traits (biocompatibility, biodegradability, hydrophilicity, and the porous structure similar to the extracellular matrix) [83]. They are composed of 90 wt% water and 10 wt% different nature biopolymers. This high water content produces soothing and cooling effects, which reduce the perceived pain. Hydrogels stimulate the healing process through their moisture exchanging actions, which generate a proper microclimate between the dressing and the injury bed [74]. Depending on their composition, hydrogel-based dressings present a high power to swallow up to 1 kg of injury exudate per gram of dressing [84]. Thus, hydrogel-based dressings furnish optimal moisture on the lesion site, which has various advantages: to avoid the injury from drying out, to mitigate the pain perception, to damage the fibrin and dead tissues, and to allow the communication between target cells and growth factors [85].

Regarding the polymeric component, hydrogels can be produced from natural polymers (cellulose and its derivatives, collagen, hyaluronic acid, chitosan and its derivatives, gelatin, alginate, keratin, fibrin, pectin, elastin, dextran, chitin, and gums) and synthetic polymers (polyvinyl alcohol, polylactic acid, polyethylene oxide, polyglycolic acid, polyacrylic acid, poly ε-caprolactone, polyethylene glycol, polyacrylamide, vinyl acetate, N-vinyl-2 pyrrolidone, 2-hydroxyethyl methacrylate, methoxyl polyethylene glycol, ethylene glycol diacrylate, and poloxamer) [78, 83].

Hydrogels are colorless and odorless; they also exhibit the highest capacity to absorb fluids in saline medium, a high absorbency under load, low price, proper stability, and durability during the storage and in swelling conditions, neutral pH after swelling in water, nontoxicity, and photostability [75]. Hydrogels allow an excellent mechanical safety, a suitable gases exchange (CO2 and O2), the stimulation of angiogenesis, and the absorption of local exudates; thus, epithelial cells can flourish, and the healing process accelerates to restore the skin layers with minimal scars. Also, hydrogels exhibit non-adhesive characteristics, malleability, and smoothness, so they are easy to applicate and remove without tissue impairment [86].

Moreover, the transparent structure of these dressings allows a suitable evaluation of the wound healing progress, without the dressing being removed. Therefore, hydrogel-based dressings are the first option to treat dry, necrotic lesions, superficial

#### **Figure 2.**

*The action mode of hydrogel-based dressing on cutaneous lesion for accelerating the wound healing process.*


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


**Table 1.** *Recent studies regarding the development of new hydrogel dressings based on different polymers composition and bioactive agents for tissue regeneration.*

#### *Hydrogels - From Tradition to Innovative Platforms with Multiple Applications*

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

injuries (burns and skin tears), surgical wounds, radiation burns, sloughy and dehydrated lesions, and shallow ulcers. Depending on the hydration level required by the lesion, hydrogel dressings need to be changed every 1–3 days [87]. The schematic illustration of the action mode of a hydrogel-based dressing on cutaneous lesion for accelerating the wound healing process is illustrated in **Figure 2**.

## **3.4 Recent studies regarding the development of new hydrogel-based dressings for damaged skin regeneration**

Hydrogel-based dressings are bioactive dressings, which are extensively used to cure different etiologies wounds because they furnish an optimum pH, suitable exchange of gases, proper regulation of temperature, and adequate local moisture, accelerating the fibroblasts' proliferation and angiogenesis [88]. These dressings present biomimetic characteristics, which make them suitable vehicles for sustained release of various bioactive agents, such as plants extracts, growth factors, nucleotides, inorganic compounds, and analgesic, anti-inflammatory, anesthetic, or antimicrobial active substances, ideal for scaffolds that target the fundamental structures involved in the healing process of the injured skin. Therefore, hydrogel-based dressings can reduce, prevent, and treat the tissue maceration, pain, inflammation, and infection that usually accompany a skin lesion [87]. Recent studies regarding the development of new hydrogel dressings based on different polymers composition and bioactive agents for tissue regeneration are summarized in **Table 1**.

## **4. Conclusions**

Cutaneous lesions care leads to a vast socioeconomic burden, with a huge impact on the patient's quality of life. Thus, this chapter presents a brief approach of hydrogels, which are the most outstanding competitors for the development of new wound dressings from all five classes of modern (advanced) dressings. Hydrogels have attracted the attention of researchers due to their particular 3D structure similar to the extracellular matrix, which has a high capacity to absorb large amounts of water and biological fluids, and which can also retain in their network external microorganisms. These dressings assure optimal moisture at the wound site and a cooling effect, being so comfortable for the patient. Furthermore, hydrogels exhibit a self-healing power, interactive structure, biocompatibility, biodegradability, low cost, nontoxicity, bioadhesion, conductivity, elasticity, softness, swelling behavior, transparency, stimuli-responsive ability, and controlled release of various bioactive agents. As a result of the last feature, this chapter also emphasizes recent studies regarding the development of new wound dressings manufactured using different polymeric supports loaded with various therapeutic agents to stimulate the regeneration of impaired skin tissues.

### **Acknowledgement**

This work was financially supported by "Carol Davila" University of Medicine and Pharmacy Bucharest, Romania, through Contract no. CNFIS-FDI-2022-0253, funded by the Romanian Ministry of Education.
