**1. Introduction**

As the largest organ system in the human body, the skin plays a vital role in maintaining the body's physiological stability, protecting the skin from external stimuli, preventing infection, and maintaining fluid balance. Therefore, skin wound healing is an important step in the survival to complete wound closure [1]. Although human skin can heal itself after injury, this is limited to superficial wounds. In cases such as deep burns or diabetes, the wound's self-healing ability is limited, and supportive methods are needed to accelerate and protect the wound healing process. Current conventional approaches to wound treatment including the application of different types of dressings, electrical stimulation therapy, skin grafting, and negative pressure wound therapy (NPWT) have proven beneficial, but they also have certain limitations [2].

Since O. Wichterle et al., reported the first case of hydrophilic gel in 1960, the results of the application of hydrogel in wound healing have become increasingly abundant [3–9]. More and more research results show that hydrogels have the ability to deliver drugs, cytokines, and growth factors as carriers, which will greatly accelerate wound healing. In addition, compared with traditional dressings, the non-adhesive nature of the hydrogel avoids secondary damage, and its 3D network structure is conducive to absorbing wound exudate while maintaining an ideal moist environment [10–13]. In view of this, hydrogels have gradually become ideal wound dressings in recent years and show good prospects in the treatment of burns and other skin injuries [14, 15]. In this chapter, we describe advanced hydrogels for wound healing and enhanced skin repair.

#### **1.1 Development of injectable hydrogel**

To date, a plethora of biomaterials as wound dressings for different clinical treatment protocols have been developed, which may be composed of synthetic or natural materials, or may be a hybrid of the two. Naturally occurring polymers, such as sodium alginate (SA), chitosan (CS), gelatin, and hyaluronic acid (HA), are biocompatible and biodegradable, which allow adhesion and coordination of cellular responses [16]. Unfortunately, natural hydrogels suffer from some limitations, such as not having strong mechanical properties and significant batch-to-batch variability [17]. In contrast, synthetic polymers such as polyvinyl alcohol (PVA), polyacrylamide (PAM), and polyethylene glycol (PEG) have become increasingly popular due to their strong mechanical properties, customizable structures and low immunogenicity [18]. However, the application of synthetic polymers in the field of biomedicine should pay attention to the rejection of the body. Therefore, more complex hydrogels were synthesized. Currently, the material design of hydrogels usually combines natural biopolymers and synthetic polymers to overcome the limitations brought by a single polymer [18]. Hydrogels are formed by cross-linking polymer chains dispersed in an aqueous medium, and the cross-linking methods mainly include physical entanglement, ionic interactions, and chemical cross-linking (**Figure 1**) [19]. Physical crosslinking is usually non-permanent, not as stable as chemical cross-linking, and has cross-linking reversibility, but it is sufficient for polymer chains to aggregate to form gel substances that are insoluble in aqueous media. Due to the covalent bonds between different polymer chains, chemically cross-linked gels have excellent mechanical strength because they are mainly connected by covalent bonds, but their preparation requires the addition of chemical initiators or cross-linking agents. It has been reported that the cross-linking agent has certain toxicity, so the cross-linking agent used to prepare the hydrogel should be extracted from the hydrogel before use, which increases the complexity of the use of chemically cross-linked gel [20]. Electron beam (EB) radiation cross-linking technology can overcome the above defects, which belongs to the grafting in chemical cross-linking and is more stable than the physical cross-linking network structure. Furthermore, when using radiation crosslinking, neither initiators nor crosslinking agents are required, making it safer, softer, and more stretchable than traditional chemical crosslinking [21]. Work in the late 1990s showed that hydrogel precursors can be injected via standard syringes without the need for pre-molding and the use of highly invasive surgical procedures to deliver the material to the target site. Injectable hydrogels have received increasing attention in recent years due to their excellent self-healing ability and minimal invasiveness [22]. Injectable hydrogel technology can better reproduce the complex extracellular

*Integrated Optical Coherence Tomography and Deep Learning for Evaluating of the Injectable… DOI: http://dx.doi.org/10.5772/intechopen.106006*

**Figure 1.**

*Cross-linking of hydrogels. (a to d) physical cross-linking. (a) Thermally induced entanglement of polymer chains. (b) Molecular self-assembly. (c) Ionic gelation. (d) Electrostatic interaction. (e) Chemical cross-linking. Reprinted with permission from reference [19].*

environment and maintain cell viability, thereby enabling adequate delivery of cells and therapeutic small molecules, which enables the development and optimization of novel therapeutic injectable Hydrogels [23, 24].

Gelatin is inexpensive and readily available and has good cell adhesion [25]. Alginates are commonly used in the treatment of deep second-degree burns due to their excellent biological properties, exudate absorption potential, and ability to maintain a moist wound environment [26–28]. In addition, carboxymethyl cellulose (CMC) contains a large number of carboxymethyl groups, which facilitates polymerization with other material [29, 30]. Their combined strengths make up for the deficiencies of one or both of these natural polymers for applications.

The EB radiation cross-linking mechanism in **Figure 2** is proposed for crosslinking of injectable 3D-PH. The radiation energy of EB is mainly absorbed by water in aqueous solution, and the radiation decomposition of water mainly produces reactive species such as hydroxyl radicals (OH) (**Figure 2a**) [32]. Amino acid residues in gelatin molecules are easily self-oxidized to form aldehyde groups, and aldehyde groups can cross-link with amino acids on gelatin molecules to form Schiff bases (**Figure 2b**), which is the first cross-linked network. Injectable 3D-PH

#### **Figure 2.**

*Mechanism of EB radiation crosslinking of injectable 3D-PH. (a) Ionizing radiation reaction equation of water in polymer aqueous solution. (b) Gelatin self-crosslinking to form the fifirst network of injectable 3D-PH. (c) the crosslinking mechanism of alginate and CMC under EB irradiation. Reprinted with permission from reference [31].*

Furthermore, OH- is considered to be a very reactive species, which can remove H from alginate and CMC carbon chains, inducing the formation of alginate-derived radicals, CMC-derived radicals, and HO. Subsequently, the radicals recombine to form new covalent bonds between the carbon chains (**Figure 2c**), which is a second cross-linked network. Hydrogen bonds formed between the injectable 3D-PH stabilize the chemical structure of the hydrogel. The new bonds formed during electron beam irradiation made the molecular chains of the hydrogel connect more tightly. The double-crosslinked network structure triggered by EB and Schiff base can significantly strengthen the hydrogel. These results demonstrate that EB irradiation cross-linking injectable 3D-PH can form a stable double-cross-linked network structure [31].

In view of this, our team designed an injectable 3D-PH via EB radiation crosslinking gelatin-alginate-carboxymethyl cellulose solution, which developed by green materials and facile applicable method (**Figure 3a**). In another study, Zhang et al. synthesized dopamine-modified gelatin@Ag nanoparticles (Gel-DA@Ag NPs) by chemical grafting for wound healing as shown in **Figure 3b** [33]. For the first time, they found that the biomineralization ability of gelatin can be enhanced with dopamine-modified gelatin (Gel-DA). This biomineralization-enhancing strategy provides a new strategy for developing organic and inorganic hybrid multifunctional *Integrated Optical Coherence Tomography and Deep Learning for Evaluating of the Injectable… DOI: http://dx.doi.org/10.5772/intechopen.106006*

**Figure 3.**

*Schematic diagram of the preparation of hydrogels. (a) 3D-PH. (b) Gel-DA/GG@Ag hydrogels. Reprinted with permission from reference [31, 33].*

hydrogels. Among the two different materials, gelatin plays different roles, the former mainly induces platelet activation for wound hemostasis and the latter mainly acts as a biomineralizer combined with metal nanoparticles, resulting in different functional localization.
