# Bioactive Glasses for Soft and Hard Tissue Healing Applications--A Short Review
## 3 BGs in Tissue Healing
### BGs in Soft Tissues Healing
#### 3.1.2 BGs Formulations Applied in Soft Tissues Healing
\\ \hline  & & & & - & The prepared films distinctly enhanced \\  & & & & & angiogenesis-related gene expression as well as VEGF \\  & Cu-containing BG & & & & and HF-12 protein secretion of HIVECs. \\  & (Ca\({}_{12<\theta\text{D}}\)),Po-Sn  
\begin{table}
\begin{tabular}{c c c c c c} \hline
**BC Composition** & **Form** & **Obtaining Method** & **Experimental Conditions** & **Outcomes of the Study** & **Ref. ** \\ \hline BC having 75 SiO\_Sr/Cr\_(\_\)(15-C) & Co-RG nanoparticles & & In vitro on mouse fibroblast & - & The in vitro tests demonstrated that the hydrogels have excellent cell compatibility, and the hydrogels could support cell adhesion. & - \\ BC having 75 SiO\_Sr/Cr\_(\_\)(15-C) & Co-RG nanoparticles & & In vitro on mouse fibroblast & - & The incorporation of Co-RG into the GeMA hydrogel \\ mLCa  
BGs can modify inflammatory responses which occur during wound healing by polarizing macrophages toward the M2 phenotype [13]. In order to increase neo-vascularization, BGs can also stimulate the gap junction of human umbilical vein endothelial cells (HUVECs) for 7 days in in vitro settings and induce the production of angiogenic genes in these cells [47]. In vitro, the culture media containing BG 1/64, BG 1/128, and BG 1/256 significantly elevated bFGF, bFGFR, VEGF, and KDR gene expression in HUVECs at 1 day in culture, when compared to endothelial cell medium. The expression of these growth factors and receptors was unaffected by both the highest concentration, BG 1/32, and the lowest one. The stimulatory effects of BG ion extracts on growth factors and receptors were still present after 7 days of culture even if their expression, particularly that of VEGF and KDR, had diminished [48]. To investigate the effects on keratinocytes, ionic extracts from 588 BGs were employed as a model. To examine the BGs effects on barrier restoration, diabetic rats with full-thickness cutaneous wounds were treated with them. Because soluble ions such as Si, Ca, and P stimulate numerous signal transduction pathways in various cells, improving re-epithelial and restoring the natural barrier function, BGs particles were able to alter the behaviors of keratinocytes that operate as barriers [14]. By lowering the inflammatory response and driving macrophages to convert their phenotype towards M2 extreme, 4555 BG was able to stimulate the wound closure in rats after a complete thickness excision of skin. As a result, one of the mechanisms through which BG promotes wound healing may be through modulating inflammatory responses to wound healing and enhancing the paracrine interactions between macrophages and repairing cells [12]. By extending the window of opportunity for the injured to be brought to a competent medical facility, control of severe hemorrhages could reduce the fatality rate in extreme settings, such as the battlefield, natural disasters, and accident sites. In these situations, simple wound dressings are frequently insufficient to heal patients, and innovative biomaterial solutions have been developed. The intrinsic pathway, which is started by the activation of factor XII (FXII), is generally what causes BGs to positively affect coagulation. The activation of FXII by negatively charged surfaces, such as those given by BGs, can enhance the innate coagulation cascade and thus also hemostasis [49; 56]. Mesoporous BGs have a large surface area because mesopores are present in their structure, which helps absorb the blood's fluid component and draw clotting components close by [60]. As a result, the coagulation process starts. Mesopores (found inside the structure of the glass) and gaps between the glass particles produce capillary action, which aids in absorbing the blood's fluid component [56]. The greater surface area of mesoporous BGs reveals more Si-OH groups, resulting in more negatively charged surfaces. Due to the presence of silanol groups, BGs exhibit negatively charged surfaces, which activate FXII.