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Bioglass 45S5:

Intro Part 1:

Bioglass 45S5, commonly referred to by its commercial name Bioglass®, is a glass, specifically composed of 45 mol % SiO2, 24.5 mol % CaO, 24.5 mol % Na2O, and 6.0 mol % P2O5 [5].  Glasses are non-crystalline amorphous solids that are commonly composed of silica-based materials with other minor additives.  Compared to soda-lime glass (commonly used, as in windows or bottles), Bioglass 45S5 contains less silica and higher amounts of calcium and phosphorous.  The 45S5 name signifies glass with 45 weight % of SiO2 and 5:1 molar ratio of calcium to phosphorus.  This high ratio of calcium to phosphorus promotes formation of apatite crystals; calcium and silica ions can act as crystallization nuclei [2].  Lower Ca:P ratios do not bond to bone [1].  Bioglass 45S5’s specific composition is optimal in biomedical applications because of its similar composition to that of hydroxyapatite, the mineral component of bone. This similarity provides Bioglass’ ability to be integrated with living bone.

History:

Bioglass was discovered 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. 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?” 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.

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 his first paper on the subject was published in 1971 in the Journal of Biomedical Materials Research. His lab continued to work on the product for the next 10 years with continued funding from the U.S. Army. By the early 21st century, there were over 500 papers published on the topic of bioactive glasses.[20]

The first successful surgical use of Bioglass 45S5 was in replacement of ossicles in middle ear, as a treatment of conductive hearing loss. The material continues to be used in bone reconstruction applications today.[2]

Manufacturing:

There are three main manufacturing techniques that are used to create Bioglass 45S5. 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 degrees C. Platinum or platinum alloy crucibles to are used 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.

The second method is sol-gel synthesis of Bioglass. This process is carried out at much lower temperatures than the traditional melting methods. It involves the creation of a solution (sol), which is composed of metal-organic and metal salt precursors. A gel is then formed through hydrolysis and condensation reactions, and it undergoes thermal treatment for drying, oxide formation, and organic removal. Because of the lower fabrication temperatures used in this method, there is a greater level of control on the composition and homogeneity of the product. In addition, sol-gel bioglasses have much higher porosity, which leads to a greater surface area and degree of integration in the body.

The third method is microwave synthesis of Bioglass, which has been gaining attention in recent years. 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. The resulting amorphous powder is then filtered, dried  at 80 degrees C, and calcined at 700 degrees C. The advantages to this technique include the short reaction time and the ability to modify the reaction environment to produce nano-phase powders.

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 sintering glass particles that are already formed into the 3D geometry and getting them to bond the particles into a strong glass phase made up of a network of pores. Since this particular type of bioglass cannot fully sinter by viscous flow above its Tg, and due to the fact its Tg is close to the onset of crystallization, it is hard to sinter this material into a dense network.

45S5 glass also has a slow degradation and conversion to an HA-like material rate. This setback make it more difficult to get 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.

Methods of Improvement/Modifications:

Several studies have investigated methods to improve the mechanical strength and toughness of Bioglass 45S5. These include creating polymer-glass composites, which combine the bioactivity of Bioglass with the relative flexibility and wear-resistance of different polymers. Another solution is coating a metallic implant with Bioglass, which takes advantage of the mechanical strength of the implant’s bulk material while retaining bioactive effects at the surface. [10] Some of the most notable modifications have used various forms of carbon to improve the properties of 45S5 glass.

For example, Touri et al. [15] 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.

Another study carried out by Li et al. [10] looked into different properties, such as the fracture toughness and wear resistance of Bioglass 45S5. The authors loaded graphene nanoplatelets (GNP) into the glass structure through a spark plasma sintering method. Graphene was chosen because of its high specific surface area and strength, as well as its cytocompatibility and lack of interference with Bioglass 45S5’s bioactivity. The composites that were created in this experiment achieved a fracture toughness of more than double the control. In addition, the tribological properties of the material were greatly improved.