Bioactive glass

Bioactive glass under an electron microscope

Bioactive glass structure

Bioactive glass or bio - glass is a biologically active material, usually based on silicate glass , consisting of a glassy matrix and microcrystals. Bioactive glasses are mainly made from silicon dioxide with the addition of other oxides . The most famous composition of bioglass is "Bioglass 45S5", obtained from silicon dioxide, sodium oxide, calcium oxide and phosphorus pentoxide . Recent developments make it possible to obtain bioactive glasses based on boron oxide and use polyester additives.

Bioactive glasses belong to the class of ceramics that can interact with body tissues. ^[one]

Inventions

First Discoveries

Bioglass ™

Invented bioactive glass by the American scientist Larry Hench ( Eng. Larry L. Hench ). Impressed by a casual conversation with a colonel who recently returned from the Vietnam War about the lack of medical technology to save the limbs of the wounded, Hench set about creating biomaterials that could not be torn off by the human body. Methods for reconstructing bone tissue by replacing a defect with an implant to enable normal functioning of a damaged organ have been known. The problem was the implant material, which must be biocompatible with the tissue. Initially, biologically inert materials were preferred - corrosion-resistant metals, plastics, and ceramics. Materials such as titanium and its alloys , stainless steel , ceramics are non-toxic and resistant to biochemical effects of the body. However, bioinert materials were not widely used in reconstructive surgery due to the lack of bioactive coatings that exclude the inevitable rejection reactions ^[2] .

The influence of bioglass on the growth and biomineralization of osteogenic sarcoma cells SaOS-2 after 3D cell bioprinting

Hench's team found that hydroxyapatite ${\ce {Ca10(PO4)6(OH)2}}$ ${\ displaystyle {\ ce {Ca10 (PO4) 6 (OH) 2}}}$ ${\ce {Ca10(PO4)6(OH)2}}$ forms an extremely strong bond with the skeleton and is the main mineral component of bones ^[3] . Experiments with various compositions based on hydroxyapatite revealed that hydroxyapatite stimulates osteogenesis and plays an important role in the regulation of calcium phosphate metabolism in the body, and that the desired properties can be obtained if the material is given the shape of a glass with a porous structure.

In 1969, a glass sample was obtained with a molecular weight ratio of components ${\ce {SiO2(45\%) + Na2O(24{,}5\%) + CaO(24{,}5\%) + P2O5(6\%)}}$ ${\ displaystyle {\ ce {SiO2 (45 \%) + Na2O (24 {,} 5 \%) + CaO (24 {,} 5 \%) + P2O5 (6 \%)}}}$ , later named Bioglass 45S5 . Ted Greenley, assistant professor of orthopedic surgery at the University of Florida, implanted rat specimens. Six weeks later, Greenley called Hench and said that the samples could not be taken back ^[4] .

Larry Hench was able to achieve a result in which the resulting material was so integrated with the bone that it could not be removed without damaging the bone ^[5] . Hench published his first work on this subject in 1971 in the journal Biomedical Materials Research. His laboratory continued to work on the project over the next 10 years, with ongoing funding from the US Army . By 2006, scientists around the world had already published more than 500 articles on the topic of bioactive glasses ^[4] .

Larry Hench

Larry Hench was born on November 21, 1938. ^[6] In 1961, he received a bachelor's degree and in 1964 a doctorate in ceramic engineering from Ohio State University . In the late 1960s, Dr. Hench became a young professor at the Department of Materials Science and Engineering at the University of Florida , where he taught materials science for 32 years. ^[7] In 1995, he moved to the Imperial College of London as the head of the Department of Ceramic Materials, where for 10 years he was a co-founder and one of the leaders of the Center for Tissue Engineering and Regenerative Medicine. In addition to developments in the field of biomaterials, Hench conducted research in the field of electroceramics , optics, and the immobilization of nuclear waste. ^[8] Hench is the author of over 800 articles, 30 books, and 32 US patents. He also published a series of popular children's books, which in an accessible form tell about science to young children ^[9] .

Larry Hench died on December 16, 2015 at the age of 77 at his home in Fort Myers (Florida).

Science Development

After the discovery of bioactive glass in 1969, a number of researchers in the field of biomaterials initiated a series of international symposia on biomaterials, mainly devoted to materials for reconstructive surgery. As these symposia became more and more popular, the idea arose of creating a specialized organization for biomaterials. The Society For Biomaterials was officially established in the United States in April 1974 ^[10] . In March 1976, a similar society ( The European Society for Biomaterials ) was created in Europe.

Further stages of the development of bioglass are conventionally divided into four periods ^[11] :

the era of discoveries (1969-1979);
era of clinical use (1980-1995);
tissue regeneration era (1995-2005);
era of innovation (2005-20 .. years).

New directions

Borate Glass

The basic compositions used to create new bioactive glass manufacturing formulations were mainly based on a silicon dioxide matrix. This structure is most suitable for the restoration of damaged bone tissue. The bonding mechanism in such silicate-based bioglasses consists of partial dissolution due to the presence of abundant modifying oxides, which leads to the formation of a silica gel layer and subsequent precipitation of the calcium phosphate layer. In the study of other glass-forming components, borate glasses were considered. They are relatively fusible, have a significantly lower viscosity than silicate glasses, and are characterized by an elastic modulus that is greatest for glasses with a high content of alkaline oxides. With the advent of pure borate glasses, their study began for use in biomedical practices ^[12] .

Marina Richard Nathalie Camille Richard was the first to investigate the replacement ${\ce {SiO_2}}$ ${\ displaystyle {\ ce {SiO_2}}}$ on ${\ce {B_2O_3}}$ ${\ displaystyle {\ ce {B_2O_3}}}$ as a part of bioglass ^[12] . In 2000, Richard studied the rate of hydroxyapatite formation for the first borate glass in a composition similar to 45S5, but without silicon dioxide, in comparison with the basic composition of partially crystallized 45S5 glass. To assess the formation of hydroxyapatite on glass, a cell-free process was simulated. The process involved the reaction of borate glass particles in a phosphate solution. ${\ce {K_2HPO_4}}$ ${\ displaystyle {\ ce {K_2HPO_4}}}$ different molarity and initial pH at 37 ° C. Hydroxyapatite formation was best observed in a 0.1 M phosphate solution for both glasses. The reaction products were investigated using x-ray diffraction , infrared spectroscopy , scanning electron microscopy , energy dispersive spectroscopy, and inductively coupled plasma atomic emission spectrometer . The results of the cell-free model were positive and they were followed by further studies of borate bioglass. Using MC3T3-E1 bone cells, In Vivo experiments were performed that successfully demonstrated bone tissue growth around borate glass particles, very similar to tissue growth in a 45S5 Hench glass sample. A successful bioactive reaction obtained with the first glass composition without silicon dioxide opened the way to the development of other compositions for bioactive use ^[13] ^[12] .

Researchers at the University of Missouri Science and Technology, Steve Jung and Delbert Day, have tested the effects of bioactive glass of various compositions on body fluids (in particular, blood). One of the borate bioglass samples, dubbed 13-93B3, did not contain silicon dioxide, but it contained calcium. Its composition in mass equivalent included the following components: ${\ce {B2O3(53\%) + CaO(20\%) + K2O(12\%) + Na2O(6\%) + MgO(5\%) + P2O5(4\%)}}$ ${\ displaystyle {\ ce {B2O3 (53 \%) + CaO (20 \%) + K2O (12 \%) + Na2O (6 \%) + MgO (5 \%) + P2O5 (4 \%)}} }$ .

Calcium is an important factor in the regeneration of the skin and is necessary for the formation of the epidermis , while at the same time making the healing process more effective. The new invention was based on the body's ability to form fibers of a particular protein, fibrin, on damaged tissues that stop platelets and are the skeleton of a thrombus that forms. The aim of the project was to create a bio-glass that simulates the microstructure of a fibrin clot. From the composition 13-93B3, scientists made similar cotton wool nanofibers ranging in size from 300 nm to 5 microns, with high ductility. The new material is called “DermaFuse” . ^[14] . After testing on laboratory animals in 2011, clinical trials were conducted at the Phelps County Regional Medical Center (Missouri, USA) on patients with the risk of limb amputation due to wound infection . Some patients had leg ulcers that did not heal for more than a year ^[15] . DermaFuse nanofibers were used to treat wounds. Significant improvements and wound healing with virtually no scarring were observed in all twelve patients with diabetes and with indications for amputation. In addition, DermaFuse has been detrimental to E. coli , Salmonella and Staphylococcus bacteria.

Polyester components

Image of a 3D glass bioglass grill. The image occupies an area of 2.5 × 2 mm.

The limiting factor in the use of bioactive glasses is their low strength, brittleness and toughness , which does not allow them to be used to create large loaded products. in 2016, a team of researchers from Imperial College London and the University of Bicocca of Milan , developed a new bioglass characterized by the ability to carry weight and depreciation , thus simulating the physical quality of living cartilage tissue. It contains quartz and polycaprolactone , a biodegradable polyester with a low melting point. The physical properties of polycaprolactone are very close to the properties of cartilage, it has sufficient flexibility and strength. Structurally printed using a 3D printer allows structures to grow and regenerate after the introduction of cartilage cells. The biodegradable implant allows you to support the weight of the patient and provides the ability to walk without the need for additional metal plates or other implants ^[16] ^[17] .

Genetic Theory

Using bioglass, scientists are also trying to find solutions to the task of starting tissue regeneration through the activation of the body's recovery processes.

Ions released from bioactive glass upon dissolution stimulate cell genes to regenerate and self-repair.
- Genetic Theory - Larry Hench

The advanced theory has remained unproven in practice for a long time. The discovery of DNA microarray technology made it possible to take a fresh look at the mechanisms of bioactivity of glasses. The first studies of microarrays on bioactive glasses demonstrated their effect on the activation of genes associated with the growth and differentiation of osteoblasts . Support for the extracellular matrix and stimulation of cell-cell and cell-matrix adhesion were enhanced by an air-conditioned cell culture medium containing bioactive glass dissolution products ^[18] .

Laboratory analysis of five different gene array models using five different inorganic ion sources provided experimental evidence for a genetic theory of osteogenic stimulation. Controlled release of biologically active ions ${{\ce {Ca}}}$ ${\ displaystyle {{\ ce {Ca}}}}$ and ${{\ce {Si}}}$ ${\ displaystyle {{\ ce {Si}}}}$ of bioactive glasses leads to increased regulation and activation of seven gene families in osteo-progenitor cells that cause rapid bone regeneration. Scientists believe that this will allow us to develop a new generation of activating glass genes, and create them specifically for tissue engineering and tissue regeneration in place. Recent findings also indicate that the controlled release of lower ion concentrations upon dissolution of bioactive glasses can be used for angiogenesis ^[19] .

Alkaline-free Bioglasses

Despite the fact that compositions based on composition 45S5 have been clinically applied to more than 1.5 million patients, they have several drawbacks. Due to the high alkali content, the following are also observed:

High dissolution rate, causing rapid resorption, which can negatively affect the balance of bone formation leading to the formation of a gap between the bone and the implant ;
Poor sintering ability and early crystallization due to a narrow temperature range of glass formation (~ 550 ° C) and the onset of crystallization (~ 610 ° C) prevent compaction and lead to poor mechanical strength of the material;
The cytotoxic effect caused by high doses of sodium leached into the culture medium ;
For treatment with stem cells in cases of major reconstruction, the use of cell scaffolds with a certain, but inaccessible porosity 45S5 composition is required ^[20] .

To address these shortcomings, a new series of alkali-free diopside- based formulations was developed. ${\ce {CaMg(Si2O6)}}$ ${\ displaystyle {\ ce {CaMg (Si2O6)}}}$ Calcium Fluoride Phosphate ${\ce {Ca5(PO4)3F}}$ ${\ displaystyle {\ ce {Ca5 (PO4) 3F}}}$ and tricalcium phosphate ${\ce {3CaOP2O5}}$ ${\ displaystyle {\ ce {3CaOP2O5}}}$ combining in different proportions. For example, a compound called 70-Di-10FA-20TCP allows you to produce “scaffolds” for bone tissue of any desired size, unlike Bioglass 45S5.

70-Di-10FA-20TCP :

{\ce {CaMg(Si2O6)(70\%) + Ca5(PO4)3F(10\%) + 3CaOP2O5(20\%)}}

{\ displaystyle {\ ce {CaMg (Si2O6) (70 \%) + Ca5 (PO4) 3F (10 \%) + 3CaOP2O5 (20 \%)}}}

The acidity and particle size of the suspension of this material is lower, which allows to reduce dissolution to the desired limits. The best sintering ability provides complete compaction before crystallization and allows to achieve better mechanical strength of the composition. In vitro cell reactions have shown good cell viability and significant stimulation of bone matrix synthesis, which suggests the possible use of material for bone tissue regeneration ^[20] .

X-ray Contrast Bioglass

To improve imaging during x-ray diagnostics, contrast agents are used. When working with bone tissue using bioactive glasses of classical compositions, it is difficult to improve the visualization of the results of radiation research methods . X-ray contrast bio-glasses are distinguished by the presence of additional oxides in the composition, which make it possible to use glass as an X-ray contrast filler for composite materials ^[21] . As a radiopaque component in dentistry, it can be used ${{\ce {BaO}}}$ ${\ displaystyle {{\ ce {BaO}}}}$ .

Examples:

{\ce {SiO2(25-35\%) + Al2O3(10-20\%) + BaO(50-60\%)}}

{\ displaystyle {\ ce {SiO2 (25-35 \%) + Al2O3 (10-20 \%) + BaO (50-60 \%)}}}

${\ce {SiO2(67\%) + Al2O3(6{,}6\%) + BaO(16{,}4\%) + B2O3(10\%)}}$ ${\ displaystyle {\ ce {SiO2 (67 \%) + Al2O3 (6 {,} 6 \%) + BaO (16 {,} 4 \%) + B2O3 (10 \%)}}}$

However, such compositions have low radiopacity values. In addition, barium oxide is toxic and reduces the chemical resistance of glass. One solution is to use tungsten oxide instead of barium oxide and to use a second radiopaque component of strontium oxide to increase radiopacity. Also ${\ce {SrO}}$ ${\ displaystyle {\ ce {SrO}}}$ increases chemical resistance and reduces the toxicity of glasses.

Example:

{\ce {SiO2(20-45\%) + Al2O3(5-35\%) + SrO(10-30\%) + B2O3(1-10\%) + F(2-20\%) + WO3(1-10\%)}}

{\ displaystyle {\ ce {SiO2 (20-45 \%) + Al2O3 (5-35 \%) + SrO (10-30 \%) + B2O3 (1-10 \%) + F (2-20 \% ) + WO3 (1-10 \%)}}}

with a total amount of strontium oxide and tungsten oxide in the range of 20-30% ^[22]

Compositions

Базовые составы биоактивного стекла:

45S5 : ${\ce {SiO2(45\%) + Na2O(4{,}5\%) + CaO(24{,}5\%) + P2O5(6\%)}}$ ${\ce {SiO2(45\%) + Na2O(4{,}5\%) + CaO(24{,}5\%) + P2O5(6\%)}}$
58S : ${\ce {SiO2(58\%) + CaO(33\%) + P2O5(9\%)}}$ ${\ce {SiO2(58\%) + CaO(33\%) + P2O5(9\%)}}$
70S30C : ${\ce {SiO2(70\%) + CaO(30\%)}}$ ${\ce {SiO2(70\%) + CaO(30\%)}}$
S53P4 : ${\ce {SiO2(53\%) + Na2O(23\%) + CaO(20\%) + P2O5(4\%)}}$ ${\ce {SiO2(53\%) + Na2O(23\%) + CaO(20\%) + P2O5(4\%)}}$

S53P4 является единственным биоактивным стеклом, ингибирующим рост бактерий.

Производные составы биостекла и стеклокерамики (в %)
Марки и типы ™	SiO ₂	P ₂ O ₅	CaO	Ca(PO ₃ ) ₂	CaF ₂	Na ₂ O	MgO	K ₂ O	Al ₂ O ₃	Ta ₂ O ₅ / TiO ₂	Fe ₂ O ₃	B ₂ O ₃	Отличительные свойства
Bioglass 42S5.6 ^[23]	42.1	2.6	29.0	-	-	26.3	-	-	-	-	-	-
Bioglass 46S5.2 ^[23]	46.1	2.6	26.9	-	-	24.4	-	-	-	-	-	-	лучшая интеграция с тканями
Bioglass 49S4.9 ^[23]	49.1	2.6	25.3	-	-	23.8	-	-	-	-	-	-
Bioglass 52S4.6 ^[23]	52.1	2.6	23.8	-	-	21.5	-	-	-	-	-	-
Bioglass 55S4.3 ^[23]	55.1	2.6	22.2	-	-	20.1	-	-	-	-	-	-
Bioglass 60S3.8 ^[23]	60.1	2.6	19.6	-	-	17.7	-	-	-	-	-	-	фосфатная пленка не образуется
Bioglass 45S5 ^[24]	45	6	24.5	-	-	24.5	-	-	-	-	-	-	оригинальный состав Bioglass; интегрируется с костями и мягкими тканями
Bioglass 45S5F ^[24]	45	6	12.25	-	12.25	24.5	-	-	-	-	-	-
Bioglass 45S5.4F ^[24]	45	6	14.7	-	9.8	24.5	-	-	-	-	-	-
Bioglass 40S5B5 ^[24]	40	6	24.5	-	-	24.5	-	-	-	-	-	five
Bioglass 52S4.6 ^[24]	52	6	21	-	-	21	-	-	-	-	-	-
Bioglass 55S4.3 ^[24]	55	6	19.5	-	-	19.5	-	-	-	-	-	-
Bioglass 8625	?	?	?	-	-	?	-	-	-	-	?	-	высокая биосовместимость, не связываетсяс тканями, фиброзная капсуляция ; поглощает инфракрасное излучение, может быть отвержден лазером, используется для инкапсуляции RFID меток
S45PZ ^[25]	45	7	22	-	-	24	-	-	-	-	-	2
Ceravital KGC ^[24]	46.2	-	20.2	25.5	-	4.8	2.9	0.4	-	-	-	-
Ceravital KGS ^[24]	46	-	33	sixteen	-	five	-	-	-	-	-	-
Ceravital KGy213 ^[24]	38	-	31	13.5	-	four	-	-	7	6.5	-	-
Ceravital bioactive ^[23]	40-50	10-15	30-35	-	-	5-10	2.5-5	0.5-3	-	-	-	-
Ceravital nonbioactive ^[23]	30-35	7.5-12	25-30	-	-	3.5-7.5	1-2.5	0.5-2	-	-	-	-
AW GC (Cerabone) ^[24]	34.2	16.3	44.9	-	0.5	-	4.6	-	-	-	-	-	оксифторапатит / стеклокерамический волластонит; высокая прочность, используется для замены частей костей; межфазный апатит быстро образуется; связь прочнее чем сама кость.
13-93B3 (DermaFuse) ^[14]	-	four	20	-	-	6	five	12	-	-	-	53	эффективен для заживления повреждений и инфекций мягких тканей.
Bioverit ^[25]	19-54	2-10	10-34	-	3-23	3-8	2-21	3-8	8-15	-	-	-	биоактивная обрабатываемая стеклокерамика, содержащая апатит и флогофит, используемая в качестве искусственного позвонка ^[26]
Биоситалл М31 ^[27]	37.2-38.5	13.2-15.5	33.5-35.0	-	-	-	1.8-3.1	-	6.2-6.5	-	-	-	+ ZnO (4.5-5.0); заполнение костных полостей; срок резорбции 8-12 мес.
Ilmaplant L1 ^[25]	44.3	11.2	31.9	-	five	4.6	2.8	0.2	-	-	-	-

Getting

Выбор формулы

Биостекло получают в нескольких формах: суспензия, гранулы, порошок, сетка и волокна. За счет аморфности стекло можно отлить в любую из них. При изменении пропорций стеклообразующего вещества ${\ce {SiO2}}$ ${\ce {SiO2}}$ и щелочных компонентов, свойства биостекла меняются от максимальной биоактивности до биоинертности:

A. , B .:

{\ce {SiO2(35-60\%) + Na2O(5-40\%) + CaO(10-50\%)}}

{\ displaystyle {\ ce {SiO2 (35-60 \%) + Na2O (5-40 \%) + CaO (10-50 \%)}}}

- glass is biologically active, binds to bone, some compounds bind to soft tissues;

Class A bioglasses are osteoproductive. They bind to both soft tissues and bone. The hydroxyapatite layer is formed within a few hours.
Class B bioglasses are osteoconductive. It does not bind to soft tissues. The formation of a layer of hydroxyapatite takes from one to several days.

C .:

{\ce {SiO2({более}\ 65\%)}}

{\ displaystyle {\ ce {SiO2 ({more} \ 65 \%)}}}

- glass is not bioactive, almost inert, encapsulated in fibrous tissue;

D .:

{\ce {SiO2({более}\ 50\%) + Na2O({менее}\ 35\%) + CaO({менее}\ 10\%)}}

{\ displaystyle {\ ce {SiO2 ({more} \ 50 \%) + Na2O ({less} \ 35 \%) + CaO ({less} \ 10 \%)}}}

- glass biologically active, resorption within 10-30 days;

S .: when

{\ce {SiO2({менее}\ 35\%)}}

{\ displaystyle {\ ce {SiO2 ({less} \ 35 \%)}}}

- glass does not form ^[11] .

Without a special effect on the formation of a connection between bioglass and bone tissue, some ${{\ce {CaO}}}$ ${\ displaystyle {{\ ce {CaO}}}}$ can be replaced ${{\ce {MgO}}}$ ${\ displaystyle {{\ ce {MgO}}}}$ , and some ${{\ce {Na2O}}}$ ${\ displaystyle {{\ ce {Na2O}}}}$ on ${\ce {K2O}}$ ${\ displaystyle {\ ce {K2O}}}$ . Also some ${{\ce {CaO}}}$ ${\ displaystyle {{\ ce {CaO}}}}$ can be replaced ${\ce {CaF2}}$ ${\ displaystyle {\ ce {CaF2}}}$ , while the rate of glass resorption will change. To facilitate the processing of material can be added ${\ce {B2O3}}$ ${\ displaystyle {\ ce {B2O3}}}$ or ${\ce {Al2O3}}$ ${\ displaystyle {\ ce {Al2O3}}}$ . However, alumina inhibits the integration of glass into tissue; therefore, its volume in the material is limited to 1–1.5% ^[11] .

Synthesis Methods

To date, various methods have been developed for the synthesis of bioglass and its composites, including conventional melt cooling, sol-gel , self-propagating high-temperature synthesis, and microwave irradiation. To obtain a certain type of bioglass, a number of methods are used. Some of these are:

1. To obtain bio-glass in the form of porous ceramics based on calcium phosphates , mainly use:

by the method of burnable additives, which are used as flour , gelatin , collagen , chitosan , etc .;
impregnation and subsequent firing of organic (polyurethane) sponges;
foaming, for example, with the introduction of hydrogen peroxide. ^[28] .

2. A known method consisting of:

making a semi-dry mass of calcium phosphate glass powder composition: ${\ce {P2O5(39{,}1\%) + CaO(43{,}5\%) + Al2O3(4{,}35\%) + B2O3(4{,}35\%) + TiO2(4{,}35\%) + ZrO2(4{,}35\%)}}$ ${\ displaystyle {\ ce {P2O5 (39 {,} 1 \%) + CaO (43 {,} 5 \%) + Al2O3 (4 {,} 35 \%) + B2O3 (4 {,} 35 \%) + TiO2 (4 {,} 35 \%) + ZrO2 (4 {,} 35 \%)}}}$ in a 1% aqueous solution of polyvinyl alcohol ;
molding blanks by pressing under a pressure of 2.5 MPa;
firing blanks in isothermal conditions at a temperature of 950 ° C for 1 hour ^[29] .

3. The method comprising the following steps:

melting a mixture consisting mainly of ${\ce {SiO2({40-60}\%) + Na2O({5-30}\%) + P2O5({до}12\%)}}$ ${\ displaystyle {\ ce {SiO2 ({40-60} \%) + Na2O ({5-30} \%) + P2O5 ({to} 12 \%)}}}$ at a temperature of 1350 ° C;
melt cooling;
grinding the resulting glass;
the formation of a porous glass substrate by mixing the powder with a foaming agent ;
hot pressing of powder and foaming agent in vacuum ^[30] .

The composition "45S5" is obtained in the following way:

tetra-ethoxysilane and triethyl phosphate are mixed with a 1 molar nitric acid solution and hydrolysis is carried out for 60 minutes with stirring;
calcium nitrate and sodium nitrate are gradually added to the mixture, stirring for 6 hours until a clear liquid is obtained;
the mixture is kept for 5 days in a sealed container, and the result is a sol with a solids content of 35%.
impregnated with large solids porous sugarcane material (with a pore diameter of ~ 10 μm);
the material is subjected to heat treatment at 1030 ° C, while the reed matrix burns out and a porous glass-ceramic material is formed. ^[28] .

Properties

The main requirements for bioactive glass are compliance with a given level of chemical, mechanical and biological characteristics. The compositions should have a given strength, crack resistance, wear resistance and fatigue resistance. When integrated with tissues, provide stimulation of osteosynthesis and biocompatibility, there should be no reactions from the immune system ^[25] .

Chemical Properties

The absence of corrosion is the main advantage and constant property of bio-glass. Two main parameters are regulated by the composition and method of application of the material:

The property to interact with the necessary elements of the body, eliminating undesirable chemical reactions with tissues and interstitial fluids.
The property to dissolve at a controlled speed, in compliance with the estimated time laid down for the formation of the replaced tissue.

Mechanical Strength

The combination of high strength titanium with osteoconductive properties of hydroxyapatite in the implant blank ^[31] .

Indicators of mechanical strength, including fatigue , and fracture toughness of bioceramics , bio -glasses and bio -metals, which are significantly 10-100 times lower than that of natural bone tissue. This limits the possibility of using a structure made of bioactive glass to reconstruct an organ with damaged bone tissue. Bioglass is not as an auxiliary material, but as the main one used only for organs that do not carry significant physiological loads ^[2] . For example, implantation of electrodes for the restoration of hearing in case of damage to the auditory nerve or restoration of the roots of the teeth ^[25] . Usually bioglass is combined with polymers and metals. With a certain formulation and production technology, bioactive glass can be obtained in the form of the desired porous structure with given cell sizes and their orientation. Such glasses can serve as a filler or coating in absorbable polymers. The elasticity indices of the obtained composite materials correspond to the elastic constants of the bone ^[32] .

Slow cooling of the melt of glass-forming oxides according to special temperature conditions allows the glass to partially crystallize (in this case, calcium metasilicate - wollastonite is most often formed ${\ce {CaSiO_3}}$ ${\ displaystyle {\ ce {CaSiO_3}}}$ ) and get mixed, glass-crystalline materials - bio-metals, which have higher mechanical characteristics compared to glasses. Heat treatment of bioglass reduces the content of volatile alkali metal oxide and precipitates apatite crystals in a glass matrix. The obtained glass-ceramic material has a higher mechanical strength, but lower biological activity ^[26] .

Biological Activity

Interaction with interstitial fluid on the surface of bioglass and the formation of new bone tissue.

The concept of biological activity means the ability of a synthetic material to actively interact with surrounding tissues with the formation of a direct connection with them. When using a biologically active material based on substances that are initially close in chemical and phase composition to bone tissue, or capable of forming such substances on its surface as a result of biomimetic processes of interaction with surrounding tissues and body fluids, the material is perceived by the body almost as its own tissue ^{[2 ]} . The key element that provides high bioactivity for bio-glass is silicon . Hydrolysis of bioglass in interstitial fluid leads to the formation of a thin jelly-like layer of silicic acid - on the surface of the implant. Negatively charged hydroxyl groups of the surface of the silicic acid layer attract ions from the surrounding solution of interstitial fluid ${\ce {Ca^2+}}$ ${\ displaystyle {\ ce {Ca ^ 2 +}}}$ , the surface charge becomes positive, then phosphoric acid ions are deposited on the surface - a layer of hydroxyapatite grows. As a result, the transition layer between bioglass and bone can have a thickness of up to 1 mm and be so strong that a fracture will occur in any other place, but not in the fusion zone ^[33] .

Bioactive glass forms a bond with bone tissue much faster than bioceramic materials due to amorphism. An arbitrary amorphous network dissolves and interacts with the interstitial fluid much faster than the crystal lattice of a ceramic material. Thanks to this, hydroxyapatite forms faster compared to other materials ^[32] .

Changing the composition of the biomaterial, it is possible to widely change the bioactivity and resorbability of the bio-glass. If the material is bioactive - bone tissue is formed, if bioresorbable - the material is replaced by bone tissue.

Application

Bioglass based on Bioglass 45S5 is used as small or lightly loaded implants in dentistry and maxillofacial surgery . Bioglass is used in dentistry and orthopedics for the production of medical materials that stimulate the restoration and elimination of bone defects, for the formation of dental fillings and the manufacture of toothpastes. Devices made using the 45S5 composite formula are called BIOGLASS ™ implants. In partial or complete crystallization, they are called BIOGLASS-CERAMIC ™ implants ^[34] . Among the most successful commercial products are bioglasses: Cortoss ™, Rhakoss ™, NovaBone ™. ^[five]

Applications

In dentistry

To fill in periodontal defects.
To fill the holes of the extracted teeth to prevent atrophy of the contour of the alveolar ridge .
To fill in bone defects after cystectomy .
For implant reconstruction.
With deep filling of the tooth root.
With Sinus lifting - surgery to build bone in the upper jaw.

In orthopedics

To fill bone cavities after removal of cysts , bone tumors , local osteoporosis .
Substitution of elements of a removed or damaged bone during operations, injuries.
Substitution of vertebral elements in injuries, osteoporosis.

In surgery

For the healing of injuries and infections of soft tissues.

In neurosurgery

To replace elements of lost or damaged skull bones after operations, injuries.

In maxillofacial surgery

To replace elements of the maxillofacial bones and joints .
To fill the bone cavities after cystotomy and cystectomy, osteomyelitis .
With bone grafting .

In veterinary medicine

When chipping animals for radio frequency identification

Application examples of bio-glasses

RFID Bioglass Capsule

For a long time, surgeons used bioglass in the form of a powder to eliminate bone defects, filling them with small cracks. Since 2010, this powder has become the main component in the Sensodyne Repair and Protect toothpaste. This application has become the most widespread use of bioactive material. ^[sixteen]

Bioglass 8625 is a soda-lime glass used to seal implants . The material has a significant iron content, which due to its absorption of infrared radiation allows the material to polymerize under a light source. The most common use of Bioglass 8625 is in RFID transponder cases for human and animal chipping ^[35] . The U.S. Food and Drug Administration (FDA) approved the use of Bioglass 8625 in humans in 1994 .

Bioglass based on 13-93B3 - Dermafuse ™ is used in medicine and veterinary medicine . The composition works in the form of nano-fiber napkins for long-term treatment of soft tissue wounds. Adhesive based on it is used to quickly treat minor wounds. Upon contact with tissues, the glue passes from a liquid to a solid state, polymerizing within a few seconds and sealing the wound.

Biogran Biogran ™ is an osteoconductive material used to treat periodontal defects. The size of bioactive granules is in the range of 300–355 μm; they completely dissolve in the body and disintegrate as a result of the Krebs cycle . Bone tissue grows from granule to granule, quickly filling the defect with bone tissue. Full replacement with new bone occurs within 9-12 months.

Notes

↑ Medkov M.A., Grishchenko D.N. Patent RU 2 690 854 C1 "Method for producing boron-containing bioactive glass" (neopr.) . Federal State Budgetary Institution of Science Institute of Chemistry of the Far Eastern Branch of the Russian Academy of Sciences (June 6, 2019).
↑ ¹ ² ³ S.M. Barinov, V.S. Komlev. Bioceramics based on calcium phosphates : [ Russian ] . - RAS Institute of Physical and Chemical Problems of Ceramic Materials. - M .: Nauka, 2005 .-- ISBN 5-02-033724-2 .
↑ Mark Honeysuckle. What is it made of? Amazing materials from which modern civilization is built . - Litres, 2019 .-- ISBN 504011754X , 9785040117543.
↑ ¹ ² Hench, LL The story of Bioglass // Journal of Materials Science in Medicine. - 2006 .-- December ( vol. 17 , no. 11 ). - P. 967-978 . - DOI : 10.1007 / s10856-006-0432-z . - PMID 17122907 .
↑ ¹ ² Bartov M.S. Thesis "New biotechnological approaches to the creation of osteoinductive materials based on the rhBMP-2 protein obtained by microbiological synthesis in escherichia coli" (Russian) . FSBI Federal Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamalei (2015). Date of treatment July 30, 2019.
↑ Larry L. Hench obituary . Tributes.com . Date accessed August 6, 2019.
↑ Remembering Larry Hench (1938-2015 ) . Herbert Wertheim College of Engineering (01/13/2016). Date accessed August 6, 2019.
↑ Immobilization includes vitrification and enclosure of nuclear material in a ceramic matrix
↑ Imperial College London. LARRY HENCH // Reporter. - 2016. - No. 292 (February 18). - S. 14.
↑ About the Society . The Society For Biomaterials. Date of treatment July 31, 2019.
↑ ¹ ² ³ Bekir KARASU, Ali Ozan YANAR, Alper KOÇAK, Özden KISACIK. Bioactive Glasses : [ eng. ] // El-Cezerî Journal of Science and Engineering. - 2017. - No. 3 (15 July). - S. 436-471. - ISSN 2148-3736 .
↑ ¹ ² ³ Mona A. Ouis, Amr M. Abdelghany, Hatem A. ElBatal. Sintering Behavior and Property of Bioglass Modified HA-Al2O3Composite // Science of Sintering. - 2012. - Issue. 44. - S. 141-149. - DOI : 10.2298 / SOS1203265W .
↑ Marina N. Richard. Bioactive behavior of a borate glass : [ eng. ] // Missouri University of Science and Technology. - 2000. - March. - P. 140. - Electronic OCLC # 906031023.
↑ ¹ ² A material made of nanofibers is created that effectively heals wounds (neopr.) . Nano News Net (05.16.2011). Date of treatment July 31, 2019.
↑ Mo-Sci Corporation's DermaFuse: Successful wound healing with borate glass nanofibers . The American Ceramic Society (04/28/2011). Date of treatment July 31, 2019.
↑ ¹ ² David Cox. Medicine of the future: how bioglass will revolutionize surgery (rus.) . BBC Future (08/07/2017). Date of treatment July 31, 2019.
↑ Artificial cartilaginous tissue from bioglass (Russian) . ENG News - Engineering News (05/13/2016). Date of treatment July 31, 2019.
↑ Subrata Pal. Design of Artificial Human Joints & Organs . - Springer Science & Business Media, 2013 .-- S. 68. - 419 p. - ISBN 146146255X , 9781461462552.
↑ Larry L. Hench. Genetic design of bioactive glass . ScienceDirect ® . Journal of the European Ceramic Society // Volume 29 (04/07/2009). doi : S095522190800441X . Date of treatment August 4, 2019.
↑ ¹ ² José MF Ferreira, Avito Rebelo. The key Features expected from a Perfect Bioactive Glass - How Far we still are from an Ideal Composition? : [ eng. ] // Biomedical Journal of Scientific & Technical Research. - 2017 .-- 7 September. - ISSN 2574-1241 . - DOI : 10.26717 / BJSTR.2017.01.01.000335 .
↑ Medkov M. A., Grishchenko D. N., Kuryavy V. G., Sloboduk A. B. Tungsten-containing radiopaque bioactive glasses: preparation and properties = FSBEI “Institute of Chemistry FEB RAS” // Glass and Ceramics. - 2018. - No. 8 (August). - S. 40-45. - ISSN 0131-9582 .
↑ Peles A.M., Isobello Yu.N., Anyaykina N.P., Zhigar V.V., Isobello N.M., Myalik O.A. X-ray contrast glass, Patent BY 13965 C1 2011/02/28 (Russian) . The base of patents of Belarus (02.28.2011). Date accessed August 7, 2019.
↑ ¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ The biomedical engineering handbook, Volume 1 by Joseph D. Bronzino, Springer, 2000 ISBN 3-540-66351-7
↑ ¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ Biomaterials and tissue engineering by Donglu Shi p. 27, Springer, 2004 ISBN 3-540-22203-0
↑ ¹ ² ³ ⁴ ⁵ Promising inorganic materials with special functions. - The use of bioglassceramics - a course of lectures (Russian) . Faculty of Chemistry, Moscow State University. Date of treatment July 31, 2019.
↑ ¹ ² Engineering materials for biomedical applications by Swee Hin Teoh, p. 6-21, World Scientific, 2004 ISBN 9812560610
↑ Afinogenov G.E. Ivantsova, T.M. Lysenok, L.N. Patent RU 2 103 013 C1 "Composition for filling bone cavities" (Russian) . RNIITO them. R.R. Harmful (01/27/1998). Date of treatment August 5, 2019.
↑ ¹ ² Medkov M.A., Grishchenko D.N. RF patent No. 2508132 "Method for producing calcium-phosphate glass-ceramic materials" (Russian) . Freepatent.ru (February 27, 2014).
↑ Stroganova E.E., Buchilin N.V., Sarkisov P.D. Mikhailenko N.Yu.,. Patent RU 2 462 272 C2 "Method for the production of porous glass-crystalline material" (neopr.) . RCTU them. DI. Mendeleev (September 27, 2012). Date of treatment July 30, 2019.
↑ Ducheyne Paul, El-Ghannam Ahmed, Shapiro Irving. US Patent "Method of forming a porous glass substrate" . USPTO . The Trustees of the University of Pennsylvania (October 14, 1997). Дата обращения 30 июля 2019.
↑ Takamasa Onoki. Porous apatite coating on various titanium metallic materials via low temperature processing : [ eng. ] // Biomaterials Science and Engineering , IntechOpen. — 2011. — 15 September. — DOI : 10.5772/24624 .
↑ ¹ ² Лэрри Хенч, Джулиан Джонс. Биоматериалы, искусственные органы и инжиниринг тканей / А. Лушникова. — Litres, 2017. — ISBN 5457371395 , 9785457371392.
↑ В.И. Путляев. Современные керамические материалы : Московский государственный университет им. М.В. Ломоносова // Соросовский образовательный журнал. — 2004. — Т. 8, № 1. — С. 46.
↑ L. Hench, June Wilson, G. Merwin. Bioglass™ Implants for Otology (неопр.) . Материалы Первого Международного симпозиума " Биоматериалы в Отологии', Лейден, Нидерланды (21 апреля 1983). Дата обращения 31 июля 2019.
↑ RFID Transponder Glass Capsules (англ.) . SCHOTT AG. Дата обращения 30 июля 2019.

[PAT_1-1] Medkov M.A., Grishchenko D.N. Patent RU 2 690 854 C1 "Method for producing boron-containing bioactive glass" (neopr.) . Federal State Budgetary Institution of Science Institute of Chemistry of the Far Eastern Branch of the Russian Academy of Sciences (June 6, 2019).

[РАН-2] ¹ ² ³ S.M. Barinov, V.S. Komlev. Bioceramics based on calcium phosphates : [ Russian ] . - RAS Institute of Physical and Chemical Problems of Ceramic Materials. - M .: Nauka, 2005 .-- ISBN 5-02-033724-2 .

[3] Mark Honeysuckle. What is it made of? Amazing materials from which modern civilization is built . - Litres, 2019 .-- ISBN 504011754X , 9785040117543.

[history-4] ¹ ² Hench, LL The story of Bioglass // Journal of Materials Science in Medicine. - 2006 .-- December ( vol. 17 , no. 11 ). - P. 967-978 . - DOI : 10.1007 / s10856-006-0432-z . - PMID 17122907 .

[DIS1-5] ¹ ² Bartov M.S. Thesis "New biotechnological approaches to the creation of osteoinductive materials based on the rhBMP-2 protein obtained by microbiological synthesis in escherichia coli" (Russian) . FSBI Federal Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamalei (2015). Date of treatment July 30, 2019.

[6] Larry L. Hench obituary . Tributes.com . Date accessed August 6, 2019.

[7] Remembering Larry Hench (1938-2015 ) . Herbert Wertheim College of Engineering (01/13/2016). Date accessed August 6, 2019.

[8] Immobilization includes vitrification and enclosure of nuclear material in a ceramic matrix

[9] Imperial College London. LARRY HENCH // Reporter. - 2016. - No. 292 (February 18). - S. 14.

[10] About the Society . The Society For Biomaterials. Date of treatment July 31, 2019.

[ECJSE-11] ¹ ² ³ Bekir KARASU, Ali Ozan YANAR, Alper KOÇAK, Özden KISACIK. Bioactive Glasses : [ eng. ] // El-Cezerî Journal of Science and Engineering. - 2017. - No. 3 (15 July). - S. 436-471. - ISSN 2148-3736 .

[europeana-12] ¹ ² ³ Mona A. Ouis, Amr M. Abdelghany, Hatem A. ElBatal. Sintering Behavior and Property of Bioglass Modified HA-Al2O3Composite // Science of Sintering. - 2012. - Issue. 44. - S. 141-149. - DOI : 10.2298 / SOS1203265W .

[13] Marina N. Richard. Bioactive behavior of a borate glass : [ eng. ] // Missouri University of Science and Technology. - 2000. - March. - P. 140. - Electronic OCLC # 906031023.

[nano-14] ¹ ² A material made of nanofibers is created that effectively heals wounds (neopr.) . Nano News Net (05.16.2011). Date of treatment July 31, 2019.

[15] Mo-Sci Corporation's DermaFuse: Successful wound healing with borate glass nanofibers . The American Ceramic Society (04/28/2011). Date of treatment July 31, 2019.

[BBC-16] ¹ ² David Cox. Medicine of the future: how bioglass will revolutionize surgery (rus.) . BBC Future (08/07/2017). Date of treatment July 31, 2019.

[17] Artificial cartilaginous tissue from bioglass (Russian) . ENG News - Engineering News (05/13/2016). Date of treatment July 31, 2019.

[18] Subrata Pal. Design of Artificial Human Joints & Organs . - Springer Science & Business Media, 2013 .-- S. 68. - 419 p. - ISBN 146146255X , 9781461462552.

[19] Larry L. Hench. Genetic design of bioactive glass . ScienceDirect ® . Journal of the European Ceramic Society // Volume 29 (04/07/2009). doi : S095522190800441X . Date of treatment August 4, 2019.

[KEY-20] ¹ ² José MF Ferreira, Avito Rebelo. The key Features expected from a Perfect Bioactive Glass - How Far we still are from an Ideal Composition? : [ eng. ] // Biomedical Journal of Scientific & Technical Research. - 2017 .-- 7 September. - ISSN 2574-1241 . - DOI : 10.26717 / BJSTR.2017.01.01.000335 .

[21] Medkov M. A., Grishchenko D. N., Kuryavy V. G., Sloboduk A. B. Tungsten-containing radiopaque bioactive glasses: preparation and properties = FSBEI “Institute of Chemistry FEB RAS” // Glass and Ceramics. - 2018. - No. 8 (August). - S. 40-45. - ISSN 0131-9582 .

[22] Peles A.M., Isobello Yu.N., Anyaykina N.P., Zhigar V.V., Isobello N.M., Myalik O.A. X-ray contrast glass, Patent BY 13965 C1 2011/02/28 (Russian) . The base of patents of Belarus (02.28.2011). Date accessed August 7, 2019.

[biomedeng-23] ¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ The biomedical engineering handbook, Volume 1 by Joseph D. Bronzino, Springer, 2000 ISBN 3-540-66351-7

[biomat-24] ¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ Biomaterials and tissue engineering by Donglu Shi p. 27, Springer, 2004 ISBN 3-540-22203-0

[МГУ-25] ¹ ² ³ ⁴ ⁵ Promising inorganic materials with special functions. - The use of bioglassceramics - a course of lectures (Russian) . Faculty of Chemistry, Moscow State University. Date of treatment July 31, 2019.

[WS-26] ¹ ² Engineering materials for biomedical applications by Swee Hin Teoh, p. 6-21, World Scientific, 2004 ISBN 9812560610

[27] Afinogenov G.E. Ivantsova, T.M. Lysenok, L.N. Patent RU 2 103 013 C1 "Composition for filling bone cavities" (Russian) . RNIITO them. R.R. Harmful (01/27/1998). Date of treatment August 5, 2019.

[Pat-28] ¹ ² Medkov M.A., Grishchenko D.N. RF patent No. 2508132 "Method for producing calcium-phosphate glass-ceramic materials" (Russian) . Freepatent.ru (February 27, 2014).

[29] Stroganova E.E., Buchilin N.V., Sarkisov P.D. Mikhailenko N.Yu.,. Patent RU 2 462 272 C2 "Method for the production of porous glass-crystalline material" (neopr.) . RCTU them. DI. Mendeleev (September 27, 2012). Date of treatment July 30, 2019.

[30] Ducheyne Paul, El-Ghannam Ahmed, Shapiro Irving. US Patent "Method of forming a porous glass substrate" . USPTO . The Trustees of the University of Pennsylvania (October 14, 1997). Дата обращения 30 июля 2019.

[31] Takamasa Onoki. Porous apatite coating on various titanium metallic materials via low temperature processing : [ eng. ] // Biomaterials Science and Engineering , IntechOpen. — 2011. — 15 September. — DOI : 10.5772/24624 .

[ЛХиДД-32] ¹ ² Лэрри Хенч, Джулиан Джонс. Биоматериалы, искусственные органы и инжиниринг тканей / А. Лушникова. — Litres, 2017. — ISBN 5457371395 , 9785457371392.

[33] В.И. Путляев. Современные керамические материалы : Московский государственный университет им. М.В. Ломоносова // Соросовский образовательный журнал. — 2004. — Т. 8, № 1. — С. 46.

[34] L. Hench, June Wilson, G. Merwin. Bioglass™ Implants for Otology (неопр.) . Материалы Первого Международного симпозиума " Биоматериалы в Отологии', Лейден, Нидерланды (21 апреля 1983). Дата обращения 31 июля 2019.

[35] RFID Transponder Glass Capsules (англ.) . SCHOTT AG. Дата обращения 30 июля 2019.