# 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
Furthermore, protein adsorption at the surfaces of the biomaterials starts biological processes; this process is reliant on the topography and chemistry of the surface [61]. In addition, due to the fact that Ca\({}^{2+}\) ions can shorten the time for blood to clot, BGs alone can be utilized to manage severe hemorrhages [42]. More specifically, mesoporous BGs have a shorter clotting time than dense BGs, owing to the blood capillary adsorption inside the pores [50]. BGs with Trace/Doping Elements  
Recent research has shown that adding trace elements such as Ti, Sr, Ta, Ga, and Ce to the matrix of mesoporous BGs and surface-modifying them with certain polymers can enhance their biological behavior. A BG system, doped with Sr, encouraged early angiogenesis by controlling macrophage polarization to the M2 phenotypes. HUVEC's ability to produce angiogenesis was improved by a macrophage/Sr-BGs culture in conditioned media, and in vivo research indicated that Sr-doped BGs promoted early vascularization [62]. In vivo studies have demonstrated that wound healing cascade works faster when hypoxia mimicking drugs are used [63]. Co is a well-known agent which mimics hypoxiabecause it activates the hypoxia-inducible factor (HIF) pathway by stabilizing HIF-1 at ambient oxygen levels. Prolyl hydroxylase domain enzymes hydroxylate HIF-1 in normal oxygen conditions, where it is constitutively produced and continuously destroyed by proteasomes [64]. In hypoxic conditions or in the presence of a substance which mimics hypoxia, such as Co, the stabilization of HIF-1 promotes the formation of the HIF complex, which is translocated to the nucleus, and causes an increase in the expression of the genes involved in the adaptation to hypoxia. Owing to the fact that BGs (having the composition of 50 mol% SiO\({}_{2}\), 24 mol% Na\({}_{2}\)O, 24 mol% MgO, and 2 mol% CoO) and their electrospun composites and have been used to stimulate angiogenesis, these materials may be useful in applications for wound healing [65]. Comparison research showed that a mesoporous BG containing 1% Ga\({}_{2}\)O\({}_{3}\) accelerates hemostasis in vitro more effectively than CeloxTM (CX) and ACS+, two commercially available hemostats, since it may considerably increase the intrinsic pathway's activation, thrombus formation, and thrombin generation. Further evidence of the superior hemostatic activity was provided by the observation of larger platelet aggregates and a more widespread platelet pseudopodia in comparison to CX and ACS+. The polar silica framework and Ca\({}^{2+}\) ions in the matrix of the 1%Ga-MBG, as well as its large specific surface area, were thought to be responsible for the platelet adherence and activity on its surface [59]. The results of this study demonstrated that the number of adherent platelets on the hemostatic materials surfaces increased in number with the incubation time of up to 60 min. After 60 min of incubation, the number of adhering platelets to the surfaces of 1%Ga-MBG and CX increased, whereas the number of adherent platelets to the surface of ACS+ was not that high. Although there was no discernible difference in the quantity of adherent platelets between the 1%Ga-MBG and CX, the platelets attached to the BG were more active than in the case of CX, as seen by the lengthy pseudopodia presence [59]. Ta-containing mesoporous BGs were recently reported [51]. When compared to no treatment, Arista\({}^{\text{TM}}\), or mesoporous BGs without Ta, a substantial reduction in bleeding time (50% of average bleeding time) was seen in a mouse tail-cut model. In another study, different compositions of Ta-containing mesoporous BGs powders were tested using a porcine fatal liver injury model [66]. A class IV bleeding state was induced in animal subjects. Within 10 min of application, the Ta-BGs were able to halt the bleeding, whereas the bleeding continued for up to 45 min without any intervention or in the presence of a commercial agent, Arista\({}^{\text{TM}}\). The blood clots demonstrated that Ta-BGs presence had no effect on clot shape.