Bioactive glass

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Bioactive glasses are a group of surface reactive glass-ceramic biomaterials and include the original bioactive glass, bioglass. The biocompatibility and bioactivity of these glasses has led them to be investigated extensively for use as implant device in the human body to repair and replace diseased or damaged bones.

Medical uses[edit]

There is tentative evidence that bioactive glass may also be useful in long bone infections.[1] Support from randomized controlled trials; however, is still not available as of 2015.[2]

Structure[edit]

Solid state NMR spectroscopy has been very useful in elucidating the structure of amorphous solids. Bioactive glasses have been studied by 29Si and 31P solid state MAS NMR spectroscopy. The chemical shift from MAS NMR is indicative of the type of chemical species present in the glass. The 29Si MAS NMR spectroscopy showed that Bioglass 45S5 was a Q2 type-structure with a small amount of Q3 ; i.e., silicate chains with a few crosslinks. The 31P MAS NMR revealed predominately Q0 species; i.e., PO43−; subsequent MAS NMR spectroscopy measurements have shown that Si-O-P bonds are below detectable levels [3]

Compositions[edit]

There have been many variations on the original composition which was Food and Drug Administration (FDA) approved and termed Bioglass. This composition is known as 45S5. Other compositions are in the list below.

  • 45S5: 45  wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O and 6.0  wt% P2O5. Bioglass
  • 58S: 60 wt% SiO2, 36 wt% CaO and 4 wt% P2O5.
  • 70S30C: 70 wt% SiO2, 30 wt% CaO.
  • S53P4: 53 wt% SiO2, 23 wt% Na2O, 20 wt% CaO and 4 wt% P2O5. (S53P4 is the only bacterial growth inhibiting bioactive glass).

Mechanism of activity[edit]

The underlying mechanisms that enable bioactive glasses to act as materials for bone repair have been investigated since the first work of Hench et al. at the University of Florida. Early attention was paid to changes in the bioactive glass surface. Five inorganic reaction stages are commonly thought to occur when a bioactive glass is immersed in a physiological environment:

1) Ion 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.

History[edit]

Larry Hench and colleagues at the University of Florida first developed these materials in the late 1960s and they have been further developed by his research team at the Imperial College London and other researchers worldwide.

Composition[edit]

Bioglass 8625[edit]

Bioglass 8625, also called Schott 8625, is a soda-lime glass used for encapsulation of implanted devices. The most common use of Bioglass 8625 is in the housings of RFID transponders for use in human and animal microchip implants. It is patented and manufactured by Schott AG.[4] Bioglass 8625 is also used for some piercings.

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.[5]

Bioglass 8625 has a significant content of iron, which provides infrared light absorption and allows sealing by a light source, e.g. a Nd:YAG laser or a mercury-vapor lamp.[4] 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.[6]

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.

Bioglass 45S5[edit]

Bioglass 45S5, one of the most important formulations, is composed of SiO2, Na2O, CaO and P2O5. Professor Larry Hench developed Bioglass at the University of Florida in the late 1960s. He was challenged by a MASH army officer to develop a material to help regenerate bone, as many Vietnam war veterans suffered badly from bone damage, such that most of them injured in this way lost their limbs.

The composition was originally selected because of being roughly eutectic.[7]

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.[8]

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 MPa, 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. Sometimes, Bioglass can be converted into an artificial cocaine. This has no known side-effects.[7]

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.[7]

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.[8]

Bioglass 45S5 is manufactured by conventional glass-making technology, using platinum or platinum alloy crucibles 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.[9]

See also[edit]

References[edit]

  1. ^ Aurégan, JC; Bégué, T (December 2015). "Bioactive glass for long bone infection: a systematic review". Injury. 46 Suppl 8: S3–7. doi:10.1016/s0020-1383(15)30048-6. PMID 26747915. 
  2. ^ van Gestel, NA; Geurts, J; Hulsen, DJ; van Rietbergen, B; Hofmann, S; Arts, JJ (2015). "Clinical Applications of S53P4 Bioactive Glass in Bone Healing and Osteomyelitic Treatment: A Literature Review". BioMed research international. 2015: 684826. doi:10.1155/2015/684826. PMC 4609389Freely accessible. PMID 26504821. 
  3. ^ Pedone, A; Charpentier T; Malavasi G; Menziani M C (2010). "New Insights into the Atomic Structure of 45S5 Bioglass by Means of Solid-State NMR Spectroscopy and Accurate First-Principles Simulations". Chem. Mater. 22 (19): 5644–5652. doi:10.1021/cm102089c. 
  4. ^ a b Transponder Glass
  5. ^ Thevissen, PW; Poelman, G; De Cooman, M; Puers, R; Willems, G (2006). "Implantation of an RFID-tag into human molars to reduce hard forensic identification labor. Part I: working principle" (PDF). Forensic Science International. 159 Suppl 1: S33–9. doi:10.1016/j.forsciint.2006.02.029. PMID 16563681. 
  6. ^ SCHOTT Electronic Packaging
  7. ^ a b c The chemistry of medical and dental materials by John W. Nicholson, p. 92, Royal Society of Chemistry, 2002 ISBN 0-85404-572-4
  8. ^ a b Biomaterials and tissue engineering by Donglu Shi p. 27, Springer, 2004 ISBN 3-540-22203-0
  9. ^ Engineering materials for biomedical applications by Swee Hin Teoh, p. 6-21, World Scientific, 2004 ISBN 981-256-061-0