Bioglass 45S5
![](http://upload.wikimedia.org/wikipedia/commons/thumb/8/86/Bioglass_structure.gif/220px-Bioglass_structure.gif)
Bioglass 45S5 or calcium sodium phosphosilicate, is a bioactive glass specifically composed of 45 wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O, and 6.0 wt% P2O5.[1] Typical applications of Bioglass 45S5 include: bone grafting biomaterials, repair of periodontal defects, cranial and maxillofacial repair, wound care, blood loss control, stimulation of vascular regeneration, and nerve repair.[2]
The name "Bioglass" was trademarked by the
Characteristics
![](http://upload.wikimedia.org/wikipedia/commons/thumb/5/57/MorphologyofBioglass.png/220px-MorphologyofBioglass.png)
45S5 bioactive glass is white in color and is in powder form, with particulates with a median size of less than 20 microns. Its chemical composition by weight is: silica (SiO2) 43-47%, calcium oxide (CaO) 22.5-26.5%, phosphorus pentoxide (P2O5) 5-7% and sodium oxide (Na2O) 22.5-26.5%>[2]
Glasses are non-crystalline disordered solids that are commonly composed of silica-based materials with other minor additives. Compared to
This composition of bioactive glass is mechanically soft in comparison to other
History
Bioglass 45S5 is important to the field of biomimetic materials as one of the first completely synthetic materials that seamlessly bonds to bone. It was developed by Larry L. Hench in the late 1960s. The idea for the material came to him during a bus ride in 1967. While working as an assistant professor at the University of Florida, Dr. Hench decided to attend the U.S. Army Materials Research Conference held in Sagamore, New York, where he planned to talk about radiation resistant electronic materials. He began discussing his research with a fellow traveller on the bus, Colonel Klinker, who had recently returned to the United States after serving as an Army medical supply officer in Vietnam.[8]
After listening to Dr. Hench's description of his research, the Colonel asked, “If you can make a material that will survive exposure to high energy radiation can you make a material that will survive exposure to the human body?”[8] Klinker then went on to describe the amputations that he had witnessed in Vietnam, which resulted from the body's rejection of metal and plastic implants. Hench realized that there was a need for a novel material that could form a living bond with tissues in the body.[8]
When Hench returned to Florida after the conference, he submitted a proposal to the U.S. Army Medical Research and Design Command. He received funding in 1968, and in November 1969 Hench began to synthesize small rectangles of what he called 45S5 glass. Ted Greenlee, Assistant Professor of Orthopaedic Surgery at the University of Florida, implanted them in rat femurs at the VA Hospital in Gainesville. Six weeks later, Greenlee called Hench asking, "Larry, what are those samples you gave me? They will not come out of the bone. I have pulled on them, I have pushed on them, I have cracked the bone and they are still bonded in place."[8]
With this first successful experiment, Bioglass was born and the first compositions studied. Hench published his first paper on the subject in 1971 in the Journal of Biomedical Materials Research, and his lab continued to work on the project for the next 10 years with continued funding from the U.S. Army. By 2006, there were over 500 papers published on the topic of bioactive glasses from different laboratories and institutions around the world.[8] The first successful surgical use of Bioglass 45S5 was in replacement of ossicles in the middle ear as a treatment of conductive hearing loss, and the material continues to be used in bone reconstruction applications today.[1]
Other uses include cones for implantation into the jaw following a
Applications
Bioglass 45S5 is used in jaw and orthopedics applications, in this way it dissolves and can stimulate the natural bone to repair itself. Bioactive glass offers good osteoconductivity and bioactivity, it can deliver cells and is biodegradable. This makes it an excellent candidate to be used in tissue engineering applications. Although this material is known to be brittle, it is still used extensively to enhance the growth of bone since new forms of bioactive glasses are based on borate and borosilicate compositions. Bioglass can also be doped with varying quantities of elements like copper, zinc, or strontium which can allow the growth and formation of healthy bone. The formation of neocartilage can also be induced with bioactive glass by using an in vitro culture of chondrocyte-seeded hydrogels and can serve as a subchondral substrate for tissue-engineered osteochondral constructs.[1]
The borate-based bioactive glass has controllable degradation rates in order to match the rate at which actual bone is formed. Bone formation has been shown to enhance when using this type of material. When implanted into rabbit femurs, the 45S5 bioactive glass showed that it could induce bone proliferation at a much quicker rate than synthetic
Bioactive glass was applied to medical devices to help restore the hearing to a deaf patient using Bioglass 45S5 in 1984. The patient went deaf due to at ear infection that degraded two of the three bones in her middle ear. An implant was designed to replace the damaged bone and carry sound from the eardrum to the cochlea, restoring the patient's hearing. Before this material was available, plastics and metals would be used because they did not produce a reaction in the body; however, they eventually failed because tissue would grow around them after implantation. A prosthesis made up of Bioglass 45S5 was made to fit the patient and most of the prosthesis that were made were able to maintain functionality after 10 years.[10] The Endosseous Ridge Maintenance Implant made of Bioglass 45S5 was another device that could be inserted into tooth extraction sites that would repair tooth roots and allow for a stable ridge for dentures.[11]
Another area in which bioactive glass has been investigated to use is
Mechanism of action
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When implanted, Bioglass 45S5 reacts with the surrounding physiological fluid, causing the formation of a hydroxyl carbonated apatite (HCA) layer at the material surface. The HCA layer has a similar composition to
- Alkali ions (ex. Na+ and Ca2+) on the glass surface rapidly exchange with hydrogen ions or hydronium from surrounding bodily fluids. The reaction below shows this process, which causes hydrolysis of silica groups. As this occurs, the pH of the solution increases.
- Si⎯O⎯Na+ + H+ + OH− → Si⎯OH+ + Na+ (aq) + OH−
- Due to an increase in the hydroxyl (OH−) concentration at the surface (a result of step 1), a dissolution of the silica glass network occurs, seen by the breaking of Si⎯O⎯Si bonds. Soluble silica is transformed to the form of Si(OH)4 and silanols (Si⎯OH) creation occurs at the material surface. The reaction occurring in this stage is shown below:
- Si⎯O⎯Si + H2O→ Si⎯OH + OH⎯Si
- The silanol groups at the material surface condense and re-polymerize to form a silica-gel layer at the surface of Bioglass. As a result of the first steps, the surface contains very little alkali content. The condensation reaction is shown below:
- Si⎯OH + Si⎯OH → Si⎯O⎯Si
- Amorphous Ca2+ and PO43− gather at the silica-rich layer (created in step 3) from both the surrounding bodily fluid and the bulk of the Bioglass. This creates a layer composed primarily of CaO⎯P2O5 on top of the silica layer.
- The CaO⎯P2O5 film created in step 4 incorporates OH− and CO32− from the bodily solution, causing it to crystallize. This layer is called a mixed carbonated hydroxyl apatite (HCA).
- Growth factors adsorb (adsorption) to the surface of Bioglass due to its structural and chemical similarities to hydroxyapatite.
- Adsorbed growth factors cause the activation of M2 macrophages. M2 macrophages tend to promote wound healing and initiate the migration of progenitor cells to an injury site. In contrast, M1 macrophages become activated when a non-biocompatible material is implanted, triggering an inflammatory response.[19]
- Triggered by M2 macrophage activation, mesenchymal stem cells and osteoprogenitor cells migrate to the Bioglass surface and attach to the HCA layer.
- Stem cells and osteoprogenitor cells at the HCA surface differentiate to become osteogenic cells typically present in bone tissue, particularly osteoblasts.
- The attached and differentiated osteoblasts generate and deposit extracellular matrix (ECM) components, primarily type I collagen, the main protein component of bone.
- The collagen ECM becomes mineralized as normally occurs in native bone. Nanoscale hydroxyapatite crystals form a layered structure with the deposited collagen at the surface of the implant.
- Following these reactions, bone growth continues as the newly recruited cells continue to function and facilitate tissue growth and repair. The Bioglass implant continues to degrade and be converted to new ECM material.
Manufacturing
There are two main manufacturing techniques that are used for the synthesis of Bioglass. The first is melt quench synthesis, which is the conventional glass-making technology used by Larry Hench when he first manufactured the material in 1969. This method includes melting a mixture of oxides such as SiO2, Na2O, CaO and P2O5 at high temperatures generally above 1100-1300 °C.[20] Platinum or platinum alloy crucibles are used to avoid contamination, which would interfere with the product's 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. However, the scaffolds that result from melt quench techniques are much less porous compared to other manufacturing methods, which may lead to defects in tissue integration when implanted in vivo.[21]
The second method is
Newer methods include flame and microwave synthesis of Bioglass, which has been gaining attention in recent years. Flame synthesis works by baking the powders directly in a flame reactor.[23] Microwave synthesis is a rapid and low-cost powder synthesis method in which precursors are dissolved in water, transferred to an ultrasonic bath, and irradiated.[24]
Shortcomings
A setback to using Bioglass 45S5 is that it is difficult to process into porous 3D scaffolds. These porous scaffolds are usually prepared by
45S5 glass also has a slow degradation and rate of conversion to an HA-like material. This setback makes it more difficult for the degradation rate of the scaffold to coincide with the rate of tissue formation. Another limitation is that the biological environment can be easily influenced by its degradation. Increases in the sodium and calcium ions and changing pH is due to its degradation. However, the roles of these ions and their toxicity to the body have not been fully researched.[1]
Methods of improvement
Several studies have investigated methods to improve the mechanical strength and toughness of Bioglass 45S5. These include creating polymer-glass
For example, Touri et al. developed a method to incorporate carbon nanotubes (CNTs) into the structure without interfering with the material's bioactive properties. CNTs were chosen because of their large aspect ratio and high strength. By synthesizing Bioglass 45S5 on a CNT scaffold, the researchers were able to create a composite that more than doubled the compressive strength and the elastic modulus when compared to the pure glass.[26]
Another study carried out by Li et al. looked into different properties, such as the
See also
References
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- ^ United States National Institutes of Health, National Library of Medicine, SENSODYNE REPAIR AND PROTECT - stannous fluoride paste.
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- ^ a b c Bakry, A.S. "Evaluation of new treatment for incipient enamel demineralization using 45S5 Bioglass". Dental Materials. 30: 341–320.
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- ^ BioMin is the trade name for a brand of toothpaste. Not to be confused with the agricultural products company Biomin.
- ^ Toothpaste for naughty boys and girls. Br Dent J 227, 430 (2019). https://doi.org/10.1038/s41415-019-0749-x
- ^ .
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- ^ Roszer, T. "Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms". Mediators of Inflammation.
- ^ a b Deliomanli, Aylin M.; Yildirim, Mehmet (2016). "Sol-gel synthesis of 13-93 bioactive glass powders containing therapeutic agents" (PDF). Journal of the Australian Ceramic Society. 52[2]: 9–19.
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