**4. Methods of obtaining**

The most methods used for bioglass nanoparticles obtain are: quenching method, sol–gel, flame synthesis, microwave irradiation and microemulsion. Two main process that can synthesize the biomaterial are the melt quenching method and sol–gel.

#### **4.1 Quenching method**

The melt queching method can synthesize bioglass in a short time, by heating the initial precursors to high temperatures and following special rules. The preparation process proposed by Hench by melting is based on the following steps:


The role of annealing is to create the conditions for the formation of microcrystals, thus obtaining a bioactive glass–ceramic.

The melt quenching method synthesis was also carried out by Shams et al. in 2018. Bioglass nanoparticles were prepared from analytical grade SiO2, Na2CO3, CaCO3, and P2O5 precursors. As an example from the literature [21]: the precursors were mixed in 53.0 SiO2:23.0 Na2CO3:20.0 CaCO3:4.0 P2O5 molar ratios followed by milling in an agate mortar [22]. The blend was mixed in a jar for several hours and then pressed into discs with 10 mm in diameter using a hydraulic press apparatus. Than the samples were placed in an alumina crucible and heat treated in the furnace [21].

In **Figure 5** we can see the thermal program: melting at 1400°C for 3 hours - resulting molten material, then quenched in distilled water to produce glass frit. The glass frit was than dried in an oven at 80°C for 5 hours. The dried glass frit was milled in a Retch PM400 milling machine using zirconia cups for 6 h to obtain the bioglass powder [21]. FESEM micrograph of bioglass nanoparticles, includes spherical particles with a wide size distribution from 100 to 800 nm [21].

Although the melt technique is a fast method, the resulting glass usually has a low specific surface area value. According to previous research, the specific surface area value is a key factor affecting bioglass bioactivity. Increasing the specific surface area can increase the surface reaction between the artificial material and the physiological environment, thereby increasing the formation of the HA layer.

#### **4.2 Sol–gel method**

One of the most common method - the sol–gel process is well known for obtaining synthetic materials, like silicate and oxide systems and respectively thin films, coatings, nanoparticles, and fibers. The sol–gel reactions takes place at low temperatures and involves the synthesis of a solution (sol), usually consisting of metal– organic and/or metal salt precursors followed by gelling by chemical reactions, or


**Table 3.** *Heat treatment temperatures for Hench glasses.* *New Trends in Bioactive Glasses for Bone Tissue: A Review DOI: http://dx.doi.org/10.5772/intechopen.100567*

**Figure 5.** *The furnace temperature programming. Image adopted from [21].*

aggregation, and finally thermal treatment for drying, removal of organic substances, and sometimes crystallization and cooling. Some ions (magnesium, zirconium, zinc, silver, titanium, boron) can be also added to the bioactive glass in order to enhance glass functionality and bioactivity. However, bioactive glass is difficult to synthesize on a nanoscale with the addition of ions [22].

The sol–gel method can synthesize bioglass at lower temperatures, has a porous structure, and a high specific surface area value which can increase the bioactivity of synthetic materials.

The raw materials used in the sol–gel method are alkoxide precursors or soluble inorganic salts derived from the oxide components of the glasses.

If a glass is prepared in the SiO2-CaO-P2O5 ternary system, the precursors used may be:


The following factors are considered: the raw materials are added dropwise, under continuous stirring; the pH is adjusted with nitric acid to 2–3 thus taking place an acid catalysis; the soil thus obtained is left to gel for a few hours in an oven at 60° C.

The advantages of the sol–gel method are:


Kumar et al. [23] synthesizing bioglass nanoparticles (SiO2 (60%)-CaO (30%) -P2O5 (10%)) through the sol–gel method. The synthesis of bioglass nanoparticles was carried out by mixing TEOS (4.054 g) with ethanol using a magnetic stirrer for one hour at room temperature. In separate containers, calcium nitrate tetrahydrate (2.372 g) and phosphate pentoxide (0.267 g) were dissolved in distilled water and stirred each with a magnetic stirrer for 30 minutes at room temperature as well. After one hour, the solution containing calcium was added dropwise to the solution containing TEOS, as well as the solution containing the phosphate. After that, ammonia solution was added to the mixture to maintain pH 11. The mixture was then put in an incubator for 48 hours to obtain the gel. The obtained gel was placed in an oven at 100°C to dry [23]. The result of TEM analysis shows that the shape of the bioglass nanoparticles is irregular at the nano and micro scales due to the presence of agglomeration, the particle size varies from 200 to 500 nm, average surface area of the bioglass nanoparticles measured using BET with N2 was 10.4 m2 /g. The larger the particle size, the smaller the surface area.

Another study made by Durgalakshmi et al., by mixing tertraethyl orthosilicate (TEOS) and HNO3 as an acid medium, then added alcohol to help the hydrolysis process. Gel formation occurred after 30 minutes of mixing. At 20 minute intervals, other reagents are added to the mixture such as phosphoric acid, calcium nitrate, and sodium hydroxide. The solution was mixed for 4 hours to obtain a homogeneous gel. After the hydrolysis process is complete, the sol is stored at 70°C for 24 hours, and then the dry white powder is taken at 600°C for 2 hours [24]. Scanning electron microscope analysis shows that the particles do not have a well-defined shape, having less than 100 nm in length [24]. The large particles of over 200 nm could be formed due to particle agglomeration during sintering [25].
