**8. Wound healing process**

Haemostasis, inflammation, migration, proliferation, and remodelling are the five stages of wound healing (**Figure 3**), [3, 68–80]. When an injury to the skin occurs, haemostasis and inflammation occur. Fibrinogen, a major component of the skin's connective tissue, aids in the coagulation of exudates and blood clotting in wounds to avoid bleeding [3, 73, 80, 81]. The inflammatory process occurs concurrently with the haemostasis phase, in which the phagocytic cells release proteases and reactive oxygen species, which clean the wound of debris and protect it from bacterial infection [3]. Blood monocytes transform into tissue macrophages at the wound site, releasing growth factors and cytokines that attract fibroblasts, endothelial cells, and keratinocytes to help repair damaged blood vessels. The epithelial cells migrate towards the wound site to replace dead cells during the migration process. The wound is fully covered by epithelium during the proliferation stage, and formation of granulating tissues starts. Tissue remodelling is the final step, in which fibroblasts fully cover the wound's surface as a new layer of skin. There is no evidence of wound in this process, which is also known as the maturation phase [1, 3, 78].

Damaged skin is vulnerable to microbial infection and is unable to protect the physiological functions of internal organs [82–84]. Wound dressing will hasten skin's physiological regeneration while also preventing infections and dehydration at the wound surface [85]. Furthermore, an ideal wound dressing should have good biocompatibility [86]. As a result, a variety of wound dressings in various types have recently appeared, the majority of which are made up of natural macromolecules such as chitosan, cellulose, alginate, and collagen [87–89]. Alginate is widely used in the pharmaceutical and biomedical fields as a natural biocompatible polysaccharide. Alginate has also been used as a wound dressing in the past. While alginate dressings can help with wound healing, they have poor haemostatic properties, particularly when it comes to massive haemorrhage [90]. Collagen which is the most abundant protein in animals, and it can be found in almost all soft and hard connective tissues. Collagen is also a vital constituent of the extracellular matrix (ECM), which organises itself around the cells in a logical manner.

**Figure 3.** *Steps in wound healing processes [1].*

Collagen has a high biocompatibility, a strong haemostatic activity, a higher water absorbing potential, and a low immunogenicity [91]. Collagen can also facilitate cell attachment and proliferation, affecting cellular activity and tissue function further. Collagen-based wound dressings were found to have a number of advantages in studies. The addition of collagen to alginate significantly improved the hydrogel's properties [92]. Meanwhile, the collagen–alginate composite had considerable water absorption and mechanical properties, allowing it to keep the wound surface moist as well as maintain local tissue and encourage cell adhesion and growth [93, 94]. On the other hand Collagen and alginate, on the other hand, display no antimicrobial activity. As a result, antimicrobial functionalization of collagen–alginate dressings is critical to promote wound healing and prevent secondary infection [95]. The abundance of cellulose in the biosphere, especially in herbal and bacterial sources, has made this natural polysaccharide more available. To make cellulose, D-glucose units are connected together by glycoside bonds of β(1 → 4)to form the formula (C6H10O5)n, which has three hydroxyl groups for each unite. These functional groups are specifically targeted for cellulose modifications in order to enhance biomedical applications such as wound dressing manufacturing. For example, in the case of modified bacterial cellulose/keratin nanofibrous mats through a hydrogel of tragacanth natural gum, increased fibroblast cell attachment and proliferation were observed [96]. Due to its excellent biocompatibility, nontoxicity, antibacterial properties, and haemostasis, chitosan is also considered a highly favourable material, while gelatine has excellent filmforming and water absorbing properties [86, 97–99]. In addition to all as a natural and herbal medicine, curcumin was mixed into the chitosan and alginate sponge (CA sponge) as a multifunctional agent to prevent wound infection. Curcumin (CUR), a polyphenol derived from turmeric, is a well-known wound-healing agent that has been shown to have antimicrobial, antioxidant, and anti-inflammatory properties [100–102].
