**1.2 Design points of hydrogels for wound treatment**

Given the characteristics of the wound surface, the goals of wound management seem obvious, including providing temporary wound coverage, preventing infection, and relieving scarring [34]. Because bacterial infection can hinder the regeneration of epithelial cells and the synthesis of collagen, the prevention of wound infection is an important function of wound dressings [35]. To achieve this function, some broad-spectrum antimicrobial agents are often added to hydrogels, such as silver ions/ nanoparticles (AgNPs) [36]. Zhang et al. compared the antibacterial properties of Gel-DA/GG@Ag hydrogels by spread plate method using two hydrogels with only guar gum (GG) and without silver ions (Gel-DA hydrogel) as the control group. As shown in **Figure 4b**, in the three treatments, the number of bacterial colonies in the GG and Gel-DA hydrogel did not change significantly, but in the GG@Ag hydrogel treatment group, the number of colonies of *Escherichia coli* and *Staphylococcus aureus* was significantly reduced, reflecting the antibacterial effect of AgNPs." Guo et al. synthesized a hydrogel TS-Gel-Ag-col with antibacterial and anti-inflammatory functions for wound treatment, which was prepared by muco-mimetic poloxamer 407 (F-107), polyvinylpyrrolidone, and dencichine/chitosan dialdehyde synergistic crosslinked aggregated collagen nanofibers decorated with silver nanoparticles [37]. The

#### **Figure 4.**

*Antibacterial and anti-inflammatory properties of hydrogels. (A) 3D-PH stimulate cell proliferation and suppresses inflammation in L929 cells. (B) Photographs of E. coli and S. aureus colonies after treatments and the relative survival rates with I) PBS, II) GG, III) gel-DA/GG, IV) gel-DA/GG@Ag1, V) PBS + NIR, VI) GG + NIR, VII) gel-DA/GG + NIR, and VIII) gel-DA/GG@Ag1 + NIR. Power density: 2 W cm−2, 10 min. (C) Antimicrobial effect of TS-gel-Ag-col with different F-107 contents against E. coli and S. aureus and effect of F-107 contents on the proliferation of fibroblasts on TS-gel-Ag-col at different time intervals (1 d, 3 d, and 5 d). Reprinted with permission from reference [31, 33, 37].*

addition of F-107 will make the hydrogel have a heat-reverse gelation and enhance biocompatibility, which can overcome the loss of the original native hierarchical aggregated structure present in living tissue fabricated by post-functionalization of collagen molecules [38, 39]. By comparing the inhibition zone diameters of *E. coli* and *S. aureus* affected by different types of gels, the authors found that the amount of F-107 had no significant effect on the bacteriostatic properties of TS-Gel-Ag-col. In addition, although TS-Gel-Ag-col without silver nanoparticles (AgNPs) also exhibited certain antibacterial properties due to the presence of dialdehyde chitosan, the antibacterial effect of AgNPs was more significant (**Figure 4c**). It can be seen that TS-Gel-Ag-col also enhanced the antibacterial effect of the hydrogel through AgNPs.

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

The high concentration of silver in this silver-containing hydrogel can provide a faster rate of bacterial inhibition, but at the same time cause cytotoxicity, and low concentrations have no significant cytotoxicity to cells, but the rate of inhibition is slow [40]. Therefore, when designing wound dressings, the silver content in the hydrogel needs to be carefully considered to achieve the optimal balance between low cytotoxicity and high antibacterial activity. However, given the oxidative damage and potential toxicity of silver nanoparticles in tissues, researchers prefer to directly synthesize hydrogels from materials with antibacterial properties rather than adding antibacterial agents [41–43].

The occurrence of inflammation is the basis of wound healing, but excessive expression of inflammatory mediators will cause some cells and tissues to atrophy and form chronic inflammation, thereby impairing the healing of skin wounds [44]. Therefore, the anti-inflammatory functional design of hydrogels is equally important. To investigate whether 3D-PH can block inflammatory signaling activation and promote cell proliferation, we used confocal laser scanning microscopy to quantify the expression of cell proliferation-related protein Ki-67 and inflammatory factors (IL- 6, TNF-α, etc.).The results showed that injectable 3D-PH successfully blocked inflammatory signaling activation and stimulated dermal fibroblast proliferation and migration in vitro (**Figure 4a**). Specifically, the level of Ki-67 was increased, while the expression of inflammatory factors was decreased. All of these are beneficial to accelerate the healing process of deep second-degree burn wounds in vivo [31].

Scars often appear after an injury, and scarring of various types can have longterm psychological and physical effects on patients, especially those located in frequently exposed areas [45]. Therefore, scar management is also an important part of wound management, and the ideal result is a dressing that minimizes scarring while allowing the wound to heal quickly. Injectable 3D-PH has the ability to accelerate necrotic tissue removal and wound healing [31]. As shown in **Figure 5a**, the injectable 3D-PH, coloplast wound dressing and blank control were injected into the wounds of second-degree scald. The results showed that after 20 days of treatment, the wounds treated with 3D-PH injection were almost invisible, and the healing rate was significantly higher than the other two groups (**Figure 5b**). Two other hydrogels, Gel-DA@ AgNPs and TS-Gel-Ag-col, also have great potential to repair skin tissue (**Figure 5c** and **d**). The researchers used a mouse full-thickness Staphylococcus aureus-infected wound model to demonstrate the properties of Gel-DA@Ag in promoting wound healing. It can be seen that among the groups, the gel DA/GG@Ag1 + NIR group had the best wound regeneration effect, showing an advantage on the fourth day of treatment, and significant epidermal regeneration could be observed, proving that Gel-DA/GG @Ag has the effect of intrinsically accelerating wound healing [33]. **Figure 5d** shows three types of traumatic bleeding models were synthetically utilized to evaluate the hemostatic performance of TS-Gel-Ag-col *in vivo* [37]. The results clearly showed that TS-Gel-Ag-col presented significantly faster hemostasis as compared to the commercial Helitene collagen hemostatic material. And due to the injectable nature of these two hydrogels, when a sol–gel transition occurs, the wound can be easily covered comprehensively and fit well to the injury site. In addition, the 3D porous structure of the hydrogel is important for wound healing, because the denseness of the porous material can prevent the escape of red blood cells and platelets. At the same time, the presence of hydrophilic residues in the 3D grid of the hydrogel enables the hydrogel to further absorb wound exudate and provide a hypoxic and humid healing environment, shortening the healing time of the epidermis [46, 47].

#### **Figure 5.**

*Healing of animal wounds treated with hydrogels.(a) schematic diagram of the surgical procedure. (b) Coloplast wound dressing, 3D-PH, and control group recovery of scalded wounds in rats on days 0, 5, 10, and 20. (c) Photographs of S. aureus-infected wounds with different treatments. I) Control, II) gel-DA/GG@Ag1, and III) gel-DA/GG@Ag1 + NIR. (d) Photographs of rat muscle trauma, liver and rabbit ear artery injury after TS-gel-Ag-col and TS-gel-col treatment. Reprinted with permission from reference [31, 33, 37].*

Most importantly, the 3D porous network structure of the hydrogel resembles the natural extracellular matrix, which will facilitate the adhesion of cells, tissue factors and growth factors for delivery [24].
