Bioactive glass

 ( Periodontology ) 

Bioactive glass was the first material found to create a strong bond with living bone tissue.

• 45S5: 45 wt% Silicon dioxide, 24.5 wt% Calcium oxide, 24.5 wt% Sodium oxide and 6.0  wt% P₂O₅. Bioglass
• S53P4: 53 wt% Silicon dioxide, 23 wt% Sodium oxide, 20 wt% Calcium oxide and 4 wt% P₂O₅.
• 58S: 58 wt% Silicon dioxide, 33 wt% Calcium oxide and 9 wt% P₂O₅.
• 70S30C: 70 wt% Silicon dioxide, 30 wt% Calcium oxide.
• 13-93: 53 wt% Silicon dioxide, 6 wt% Sodium oxide, 12 wt% Potassium oxide, 5 wt% Magnesium oxide, 20 wt% Calcium oxide, 4 wt% P₂O₅.

The 45S5 name signifies glass with 45 wt.% of SiO₂ and 5:1 molar ratio of calcium to phosphorus. Lower Ca/P ratios do not bond to bone. Biomaterials and tissue engineering by Donglu Shi p. 27, Springer, 2004

The key composition features of Bioglass is that it contains less than 60 mol% SiO₂, high Na₂O and CaO contents, high CaO/P₂O₅ ratio, which makes Bioglass highly reactive to aqueous medium and bioactive.

High bioactivity is the main advantage of Bioglass, while its disadvantages includes mechanical weakness, low fracture resistance due to amorphous 2-dimensional glass network. The bending strength of most Bioglass is in the range of 40–60 Megapascal, which is not enough for load-bearing application. Its Young's modulus is 30–35 GPa, very close to that of cortical bone, which can be an advantage. Bioglass implants can be used in non-load-bearing applications, for buried implants loaded slightly or compressively. Bioglass can be also used as a bioactive component in composite materials or as powder and can be used to create an artificial septum to treat perforations caused by cocaine abuse. It has no known side-effects.

The first successful surgical use of Bioglass 45S5 was in replacement of ossicles in middle ear, as a treatment of conductive hearing loss. The advantage of 45S5 is in no tendency to form fibrous tissue. Other uses are in cones for implantation into the jaw following a tooth extraction. Composite materials made of Bioglass 45S5 and patient's own bone can be used for bone reconstruction.

Bioglass is comparatively soft in comparison to other glasses. It can be machined, preferably with diamond tools, or ground to powder. Bioglass has to be stored in a dry environment, as it readily absorbs moisture and reacts with it.

Bioglass 45S5 is manufactured by conventional glass-making technology, using platinum or platinum alloy to avoid contamination. Contaminants would interfere with the chemical reactivity in organism. Annealing is a crucial step in forming bulk parts, due to high thermal expansion of the material.

Heat treatment of Bioglass reduces the volatile alkali metal oxide content and precipitates apatite crystals in the glass matrix. The resulting glass–ceramic material, named Ceravital, has higher mechanical strength and lower bioactivity. Engineering materials for biomedical applications by Swee Hin Teoh, p. 6-21, World Scientific, 2004

When S53P4 bioactive glass is placed into the bone cavity, it reacts with body fluids to activate the glass. During this activation period, the bioactive glass goes through a series of chemical reactions, creating the ideal conditions for the bone to rebuild through osteoconduction.

• Na, Si, Ca, and P ions are released.
• A silica gel layer forms on the bioactive glass surface.
• CaP crystallizes, forming a layer of hydroxyapatite on the surface of the bioactive glass.

Once the hydroxyapatite layer is formed, the bioactive glass interacts with biological entities, i.e., blood proteins, growth factors and collagen. Following this interaction, the Osteopromotive and osteostimulative processes help the new bone grow onto and between the bioactive glass structures.

• Bioactive glass bonds to bone –facilitating new bone formation.
• Osteostimulation begins by stimulating osteogenic cells to increase the remodeling rate of bone.
• Radio-dense quality of bioactive glass allows for post-operative evaluation.

In the final transformative phase, the process of bone regeneration and remodeling continues. Over time the bone fully regenerates, restoring the patient's natural anatomy.

• Bone consolidation occurs.
• S53P4 bioactive glass continues to remodel into bone over a period of years.

Bioactive glass S53P4 is currently the only bioactive glass on the market which has been proven to inhibit bacterial growth effectively. The bacterial growth inhibiting properties of S53P4 derive from two simultaneous chemical and physical processes, which occurs once the bioactive glass reacts with body fluids. Sodium (Na) is released from the surface of the bioactive glass and induces an increase in pH (alkaline environment), which is not favorable for the bacteria, thus inhibiting their growth. The released Na, Ca, Si and P ions give rise to an increase in osmotic pressure due to an elevation in salt concentration, i.e., an environment where bacteria cannot grow.

Bioglass 8625 does not bond to tissue or bone, it is held in place by fibrous tissue encapsulation. After implantation, a calcium-rich layer forms on the interface between the glass and the tissue. Without additional antimigration coating it is subject to migration in the tissue. The antimigration coating is a material that bonds to both the glass and the tissue. Parylene, usually Parylene type C, is often used as such material.

Bioglass 8625 has a significant content of iron, which provides infrared light absorption and allows sealing by a light source, e.g., a or a mercury-vapor lamp. The content of Fe₂O₃ yields high absorption with maximum at 1100 nm, and gives the glass a green tint. The use of infrared radiation instead of flame or contact heating helps preventing contamination of the device. SCHOTT Electronic Packaging

After implantation, the glass reacts with the environment in two phases, in the span of about two weeks. In the first phase, alkali metal ions are leached from the glass and replaced with hydrogen ions; small amount of calcium ions also diffuses from the material. During the second phase, the Si-O-Si bonds in the silica matrix undergo hydrolysis, yielding a gel-like surface layer rich on Si-O-H groups. A calcium phosphate-rich passivation layer gradually forms over the surface of the glass, preventing further leaching.

It is used in microchips for tracking of many kinds of animals, and recently in some human implants. The U.S. Food and Drug Administration (FDA) approved use of Bioglass 8625 in humans in 1994.

The 13-93 glass has received approval for in vivo use in the US and Europe. It has more facile viscous flow behavior and a lower tendency to crystallize upon being pulled into fibers. 13-93 bioactive glass powder could be dispersed into a binder to create ink for robocasting or direct ink 3D printing technique. The mechanical properties of the resulting porous scaffolds have been studied in various works of literature.

The printed 13-93 bioactive glass scaffold in the study by Liu et al. was dried in ambient air, fired to 600 °C under the O₂ atmosphere to remove the processing additives, and sintered in air for 1 hour at 700 °C. In the pristine sample, the flexural strength (11 ± 3 MPa) and flexural modulus (13 ± 2 MPa) are comparable to the minimum value of those of trabecula while the compressive strength (86 ± 9 MPa) and bulk modulus (13 ± 2 GPa) are close to the cortical bone values. However, the fracture toughness of the as-fabricated scaffold was 0.48 ± 0.04 MPa·m^1/2, indicating that it is more brittle than human cortical bone whose fracture toughness is 2–12 MPa·m^1/2. After immersing the sample in a simulated body fluid (SBF) or subcutaneous implantation in the dorsum of rats, the compressive strength and compressive modulus decrease sharply during the initial two weeks but more gradually after two weeks. The decrease in the mechanical properties was attributed to the partial conversion of the glass filaments in the scaffolds into a layer mainly composed of a porous hydroxyapatite-like material.

Another work by Kolan and co-workers used selective laser sintering instead of conventional heat treatment. After the optimization of the laser power, scan speed, and heating rate, the compressive strength of the sintered scaffolds varied from 41 MPa for a scaffold with ~50% porosity to 157 MPa for dense scaffolds. The in vitro study using SBF resulted in a decrease in the compressive strength but the final value was similar to that of human trabecular bone.

13-93 porous glass scaffolds were synthesized using a polyurethane foam replication method in the report by Fu et al. The stress-strain relationship was examined in obtained from the compressive test using eight samples with 85 ± 2% porosity. The resultant curve demonstrated a progressive breaking down of the scaffold structure and the average compressive strength of 11 ± 1 MPa, which was in the range of human trabecular bone and higher than competitive bioactive materials for bone repairing such as hydroxyapatite scaffolds with the same extent of pores and polymer-ceramic composites prepared by the thermally induced phase separation (TIPS) method.

Laser cladding is a method by which bioactive glass microparticles are thrust in a stream at the bulk material, and introduced to a high enough heat that they melt into a coating of material.

1. exchange in which modifier cations (mostly Na⁺) in the glass exchange with hydronium ions in the external solution.
2. Hydrolysis in which Si-O-Si bridges are broken, forming Si-OH silanol groups, and the glass network is disrupted.
3. Condensation of silanols in which the disrupted glass network changes its morphology to form a gel-like surface layer, depleted in sodium and calcium ions.
4. Precipitation in which an amorphous calcium phosphate layer is deposited on the gel.
5. Mineralization in which the calcium phosphate layer gradually transforms into crystalline hydroxyapatite, that mimics the mineral phase naturally contained with vertebrate bones.

Later, it was discovered that the morphology of the gel surface layer was a key component in determining the bioactive response. This was supported by studies on bioactive glasses derived from sol-gel processing. Such glasses could contain significantly higher concentrations of SiO₂ than traditional melt-derived bioactive glasses and still maintain bioactivity (i.e., the ability to form a mineralized hydroxyapatite layer on the surface). The inherent porosity of the sol-gel-derived material was cited as a possible explanation for why bioactivity was retained, and often enhanced with respect to the melt-derived glass.

Subsequent advances in DNA microarray technology enabled an entirely new perspective on the mechanisms of bioactivity in bioactive glasses. Previously, it was known that a complex interplay existed between bioactive glasses and the molecular biology of the implant host, but the available tools did not provide a sufficient quantity of information to develop a holistic picture. Using DNA microarrays, researchers are now able to identify entire classes of genes that are regulated by the dissolution products of bioactive glasses, resulting in the so-called "genetic theory" of bioactive glasses. The first microarray studies on bioactive glasses demonstrated that genes associated with osteoblast growth and differentiation, maintenance of extracellular matrix, and promotion of cell-cell and cell-matrix adhesion were up-regulated by conditioned cell culture media containing the dissolution products of bioactive glass.