# Bioactive Glasses for Soft and Hard Tissue Healing Applications--A Short Review
## 3 BGs in Tissue Healing  
### BGs in Soft Tissues Healing  
#### 3.1.1 Soft Tissues Healing  
Under normal medical circumstances, the body's natural regeneration process involves four overlapping stages: hemostasis, inflammation, proliferation, and tissue remodeling [31; 32]. The epidermis, specifically the stratum comeum and tight junctions (TJs) between keratinocytes, is where the skin's barrier function is located [33]. The stratum corneum, or \"corneocytes\", is the epidermis' outermost layer and is composed of terminally developed enucleated keratinocytes. To help against dehydration, poisons, and germs, the enucleated keratinocytes of the stratum corneum assemble into a brick-and-mortar construction within a lipid-rich extracellular matrix. The treatment of oral and cutaneous ulcers, as well as surgical, traumatic, and chronic wounds, are just a few of the many therapeutic applications that fall under the umbrella of wound healing. Moreover, TJs, which are made of cytosolic plaque proteins called zonula occludens and transmembrane proteins, extend from adjacent keratinocytes to create paired strands that shut the paracellular channel, preventing the flow of chemicals via the intracellular space [34]. Vasoconstriction, platelet aggregation, and blood coagulation stop bleeding quickly in a process known as _hemostasis_. An up-to-four-day period of inflammation follows, during which immune cells are enlisted to fight infection and promote capillary formation [35]. The body's natural attempt to control bleeding is called _hemostasis_ and it is achieved by vascular constriction, platelet plug formation, and coagulation. Intrinsic and extrinsic routes start the intricate enzymatic process of coagulation. These come together to form a stable blood clot along a shared channel [36]. Hemostatic dressings (hemostats) can assist in achieving hemostasis during surgical operations. Numerous commercially available biomaterial-based hemostats are being created to improve hemostasis, such as AristaTM (Bard Davol Inc., Rhode Island, RI, USA). The _inflammatory_ phase is crucial to wound healing since it greatly influences how things progress. The inflammatory phase occurs at the very beginning of wound healing and typically lasts from one hour to seven days following the injury. Different cell types, including monocyte, neutrophil, and macrophage, are involved in the inflammation phase and have the ability to secrete a variety of cytokines and chemokines [37]. Inflammatory cytokines are crucial for the immune system's response because they control immune cell infiltration, regulate the immunological response, and contribute to angiogenesis. Macrophages often have two different phenotypes of activation: (i) M1 (classically activated) and (ii) M2 (alternatively activated) [38]. While M2 macrophages are engaged in debris scavenging, tissue remodeling, and the resolution of inflammation, M1 macrophages have the ability to kill microbes and can emit large quantities of pro-inflammatory cytokines [38]. Macrophages play an important role in the vascularization by generating important angiogenic factors: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-\(\beta\) (TGF-\(\beta\)). Additionally, macrophages have the ability to secrete a range of chemokines, cytokines, and proteases that can draw endothelial cells, fibroblasts, and keratinocytes to wound sites, where they can then induce angiogenesis, collagen production, and the development of granulation tissue [38]. Activated macrophages communicate with mending cells such as fibroblasts and endothelial cells in a paracrine manner, which is why the healing of wounds depends not only on the activity of macrophages but also on these connections [38]. Several processes, such as re-epithelialization, angiogenesis, fibroblast production, and the creation of extracellular matrix (ECM) components, which result in the formation of granulation tissue and wound contraction, occur during the _proliferative_ phase [39].