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Bioactive Glasses

Introduction

• Like wheels of time, dentistry too keeps evolving and


innovating; one of such innovation is Bioglass, developed by
Hench in 1969.

• It comprises of calcium sodium phosphosilicate.

• Bioglass precipitates hydroxyapatite crystal in aqueous


solution, which has ability to bond with soft and hard tissues
of the body without rejection.

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• The bioactivity of Bioglass is due to its reactions with tissue
fluids, which initiates hydroxyapatite crystal formation.

• The properties of bioactivity along with biocompatibility


paved way for Bioglass into modern dentistry for various
purposes such as for repair of voids and defects of facial
bone, remodeling of dentoalveolar complex, etc.

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History

• Bioglass was developed by Professor Larry Hench, of University


of Florida, in 1969 with the idea of developing a material that
could bond to bone.
• Later scientists suggested for the material to be
flourished‫تزدهر‬, since the implants available were made of
metals or polymers that were bioinert and caused fibrous
encapsulation in preference to a stable bond with tissues.

• The main discovery was of a glass with the composition 46.1


mol% silicon dioxide, 24.4 mol% sodium oxide (Na2O), 26.9 mol
% calcium oxide (CaO), and 2.6 mol% phosphorus pentoxide
(P2O5), later termed Bioglass 45S5, which forms firm bond
with bone that could only be detached on breaking the bone.
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• The University of Florida used “Bioglass” as a trade name for
the original 45S5 composition. Thus, the term Bioglass is used
to refer to the 45S5 composition and is not a general term for
bioactive glass.

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Summary of the developments in Bioactive glass (BG)
research and products

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Composition

 Besides previous content in table 1, it may also contain some


of biocompatible and bioactive minerals like:
• 1. Fluorapatite
• 2. Wollastonite
• 3. Diopside
• 4. Tricalcium phosphate.

 Network modifiers, namely CaO, Na2O, and P2O5, are


generally used. However, both CaO and Na2O may be replaced
with magnesium oxide and potassium oxide, which promote
apatite crystal formation.
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 To alter the surface reactions and melting properties,
aluminum oxide and barium oxide may be added.
 Ions may be added for modifying bioactivity and antimicrobial
properties as: silicon ions, phosphorus ions, strontium ions,
silver ions, zinc ions, and fluoride ions.
• More acid-resistant fluorapatite formation is initiated, rather
than hydroxyapatite.
• Augmented remineralization of dentin and reduced possibility
of dentin-matrix degradation is initiated by fluoride coupled
with Bioglass. These attributes make fluoride vitally important
in dental applications of Bioglass.
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 There are two variants of Bioglass available, type A and type
B:
• The type A is alkali-free Bioglass, especially sodium, with a
composition of 70% diopside, 10% fluorapatite, and 20%
tricalcium phosphate. While,

• The type B variant is bioinert with silica content greater than


60% by weight.

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Compositions of different bioactive glasses

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Method of Preparation

 (1) Conventionally, glasses were prepared using melt


quenching above 1,300°C. Nevertheless, this method had a
few drawbacks such as:
• Bioactivity of the substance is reduced owing to high sintering
temperature.
• Ineffective to fabricate porous scaffolds.

• Also, heat treatment of silicon-containing Bioglass results in


release of stress from glass, thereby affecting the mechanical
properties.

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 (2) Another method of preparation of Bioglass used since
1970s is “sol-gel technique.”
• This process involves hydrolysis and condensation followed by
low-temperature heat treatment.
• This approach has encouraged manufacturers to produce
variety of glasses, differing in content and structure, E.g.
fibers, coatings, scaffolds, and nanoparticles.

• It has elevated porosity, apatite-formation ability, and more


surface area in contrast to melt quenching, which imparts
higher mechanical properties.

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Mechanism of Action

• When Bioglass is placed at the defect site, body fluids begin to


hydrate glass surface thereby initiating conversion reaction;
soon, thin layer of hydroxyapatite crystal is formed over glass
surface that thickens over time thereby inducing other body
cells to take actions as per location followed by mineralization
of the matrix (►Fig. 1).

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Properties of Bioglass

 Bioglass is biocompatible, nontoxic, and chemically stable in


biological environment.

 It has antimicrobial property as well, since it elevates the pH


and osmolarity locally, thereby creating unfavorable
environment for bacterial growth.

 Bioglass differs highly from conventional glass in its


dissolution.
• Bioglass requires a particular dissolution for its activation,
which is accomplished by addition of network modifiers like
CaO or Na2O, which makes both the surface and silica
reactive.
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 Alkali-free Bioglass coupled with zinc oxide and strontium
oxide imparts antimicrobial property against Staphylococcus
aureus and Escherichia coli.
• These features make Bioglass a classic bone alternative in
remedy for osteomyelitis, periimplant infection, sinus
augmentation, and repairing orbital floor flaws.

 As Bioglass can be incorporated into hydrophilic and


hydrophobic conditions, it may be used along with dental
implants as coating. Also, particle size influences the
antimicrobial properties; smaller-sized particles provide larger
surface area, thus increasing the antimicrobial effects.
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Advantages and Disadvantages of Bioglass

Advantages
• The chief advantage of Bioglass, which makes it a noteworthy
innovation, is the high surface speed reaction that facilitates
forming of rapid networks to the tissues.
• Its bioactive nature, broad-spectrum antimicrobial properties,
and biocompatibility are few other advantages.

Disadvantages
• However, every material has some disadvantages; the main
disadvantage of Bioglass is its low mechanical strength.

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Clinical Applications of Bioglass in Dentistry

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Application in oral care products

• Bioactive glasses have been used in various dental products


especially toothpaste.
• It has been observed that bioactive glasses are useful in the
formulation of toothpaste because they can release
antibacterial agents, stimulate remineralization and reduce
hypersensitization.
• One of the bioactive glasses is called NovaMin (calcium-
sodium-phosphate silicate) which is used as an active
ingredient in toothpaste to increase remineralization and
reduce tooth sensitivity due to release of calcium and
phosphate ions that could raise pH and lead to deposition of
calcium phosphate and its conversion to hydroxyapatite.
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• BiominF is another commercial product of bioactive glass
which includes fluoride and phosphate and induces the
formation of fluorapatite (FAP).
• It was FDA approval in 2021.

• It can control the release of calcium, phosphate, and fluoride


ions for many hours after brushing.

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Application in periodontics &
dental implants
• Periodontitis is a common chronic multifactorial inflammatory
disease of the periodontium that can cause clinical
attachment loss, alveolar bone loss, periodontal pocket, and
gingival bleeding because of loss of periodontal tissue
support.
• This condition can also lead to alveolar bone resorption and
loosening of teeth.
• Periodontitis can cause inflammation developments around
dental implants which ultimately increases the risk of implant
detachment and treatment failure. To improve the prognosis
of dental implants, reconstruction of bone defects is essential.
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• Research on dogs has shown that bioactive glass particles
have the ability to treat periodontal defects by increasing
bone mineralization.

 One of the bioactive glasses that affects bone defects is


PerioGlas which has a similar formulation to Bioglass 45S5 and
is widely used as a grafting material in bone grafts to
regenerate periodontal osseous defects. PerioGlas contains 90
to 710μm bioactive glass particles, so it can penetrate into
bone defects and stimulate bone regeneration in periodontal
surgeries.

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 Additionally, silica-based bioactive glasses have been used for
covering implants, too. It could be used as a coating material
on the surfaces of dental implants.

• Covering implants (especially titanium implants) with


bioactive glass prevents infection and inflammation around
the implants due to their antimicrobial properties. The
bioactive glasses increase titanium implants bond to bone and
promote their bioinert nature so, they reduce the total time
of treatment and improve the osseointegration.

This may allow for a wider case selection criteria together with improved
integration rates even in the more challenging medically compromised and
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Application in orthodontics

• Adhesion of orthodontic brackets can make favorable


conditions for the presence of bacteria which may lead to
demineralization of the tooth and the formation of white spot
lesions (WSLs). To prevent such conditions oral hygiene
maintenance, regular and correct brushing, and use of
fluoride toothpaste and mouth washes are recommended.

 Bioactive glasses have the ability to remineralize these white


spot lesions when incorporated in orthodontic adhesives.
• Studies found that orthodontic adhesives with bioactive glass
and fluoride could enhance the strength of apatite structure
which plays a role in preventing the formation of white spot
lesions.
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• Orthodontic bonding agents containing bioactive glasses with
silver or zinc elements have stronger antimicrobial and
remineralizing effects compared to conventional orthodontic
adhesives.

 The most important enamel damage due to orthodontic


treatment occurs in removing the residual orthodontic
adhesive after the operation.
• Slow-speed tungsten carbide is commonly used for this
purpose. QMAT3 is a novel bioactive glass that could be used
in air abrasion process to remove orthodontic adhesives with
minimal enamel damage .
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• In one study, tungsten carbide bur, QMAT3-air-abrasion, and
Bioglass 45S5-air-abrasion were examined in vitro to evaluate
enamel damage during the process of removing residual
orthodontic adhesive.
• ----------------------------The results showed that QMAT3
bioactive glass has minimal enamel damage in comparison
with Bioglass 45S5 air abrasion and tungsten carbide bur.
Therefore, QMAT3 seems to offer a conservative approach for
orthodontic adhesive removal.

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Application in endodontics

• Bioactive glasses have also been used in root canal


treatments.
• In dental pulp disorders, various treatment options such as
pulpectomy, pulpotomy, and pulp capping are present and the
materials that can be used in these treatments will play a very
effective role in the prognosis of teeth and the success of the
treatment.
 In a study on rats, a novel bioactive glass was used as a pulp
capping material after direct pulp capping. The results showed
that bioactive glass stimulated the formation of heavy dentin
bridges with inflammatory reactions similar to mineral
trioxide aggregate (MTA).
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• When microorganisms reach the pulp cavity, root canal
treatment is prescribed in which it is necessary to use a root
filler to prevent bacterial leakage as well as create a strong
sealing.

 Gutta-percha in combination with Bioglass 45S5 (Bio-Gutta)


can be used as an alternative to conventional gutta-percha in
root canal treatments. Bio-Gutta can bond to dentin walls,
does not require any sealers, and is also a biocompatible
material.

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 Also, bioactive glass can be used as a disinfectant because it
has antimicrobial effects due to increasing the pH of an
aqueous environment and calcium levels. Bioglasses can act
as topical root disinfectants in endodontics and have no effect
on dentin stability.

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Application in oral & maxillofacial surgery

• The application of bioactive glass in maxillofacial surgeries


compared to other calcium phosphate compounds such as
hydroxyapatite and tricalcium phosphate increases bone
formation both qualitatively and quantitatively and more
rapidly.
• Bioglass was approved by the US Food and Drug
Administration in 2005 as a bone stimulant.
 Bioglass has been used as a synthetic bone graft under the
commercial names Novabone in orthopedics and Perioglass in
maxillofacial surgeries. In vitro research has shown that
bioactive glass can cause bone regeneration by having effects
on bone stimulation.
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• Various commercial products of bioactive glasses including
Bioglass 45S5, Biogran, 70S30C bioactive glass, BonAlive, and
StronBone are mainly used in oral and maxillofacial surgeries.

• Biogran is widely used to treat maxillofacial injuries. It can be


used as secondary alveolar bone grafting in patients with
clefts lip and palate and for maxillary sinus augmentation
either alone or in a mixture with autogenous bone graft.

• The results showed improved microarchitecture of the graft


and decreased bone resorption volume in addition to high
quality bone formation with the addition of bioglasses.

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 Bioactive glass can be used as a scaffold for stem cells, too.
• Using bioactive glass scaffolds for adipose-derived stem cells
in order to treat craniomaxillofacial hard-tissue defects at
anatomically different sites, including frontal sinus, cranial
bone, mandible, and nasal septum showed successful
integration of the construct to the surrounding skeleton.

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Application in esthetic & restorative
dentistry
 Bioactive glasses could be used for enamel remineralization of
primary carious lesions that have not cavitated, for example
white spot lesion, may be prevented from further spreading
and demineralization. Through routine plaque removal and
fluoride deposition, operative procedures may be avoided.

• Fluoride doped with Bioglass exhibits potential usage in


dental utilization, for example, as dentifrices and restorative
materials. A Bioglass coupled with fluoride and increased
phosphate content is commercially available as BiominF,
which results in the formation of fluorapatite, in contrast to
calcium fluorite.

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 Dentin hypersensitivity is characterized by short-term and
severe toothache to thermal, chemical, or tactile stimuli.
• Dentin hypersensitivity pain can be reduced by blocking nerve
endings or by sealing dentinal tubules.
• Bioactive glasses can relieve pain during dentin
hypersensitivity by binding to collagen fibers and depositing
hydroxyapatite in order to block dentin tubules.
• PerioGlas tends to block dentin tubules and reduce dentin
tenderness pain by bonding tightly to collagen.

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 The tooth preparation for composite restorations leads to
forming a smear layer including tooth tissue debris as well as
bacteria on the tooth surface.
• Acid-etching performed to remove that smear layer & expose
dentinal tubules, activates the matrix metalloproteinases
(MMPs) which destroy the collagen network of dentin and can
cause microleakage.
• Bonding systems containing bioactive glass in comparison
with bonding systems without bioactive glass can reduce
microleakages by remineralizing the mineral-deffcient areas
and increasing the modulus of elasticity and hardness
properties at the dentin interface.
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 Bioglass As Restorative Material: Almost all of the restorative
materials available are biomimetic but not bioactive. Also,
they undergo some degree of polymerization contraction
leading to formation of microgap, thus leading to
microleakage, which affects the mechanical properties of both
tooth and the restoration.

• This microgap is often beyond the reach of routine dental


hygiene practice, thereby creating favorable environment for
microorganisms’ growth, thus leading to secondary caries and
restoration failures.

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• Resin composite with Bioglass filler exhibits antimicrobial and
bioactive properties, which prevent secondary caries.

• Resin-modified glass ionomer cement (GIC)-containing


bioactive glass has higher remineralization property. Also, it
exhibits active antimicrobial property against Candida albicans
and Streptococcus mutants.

• However, integration of Bioglass with Resin composite and


Resin-modified GIC weakens its strength and mechanical
properties thereby limiting its uses as liners and for cavities
where occlusal forces are not so strong.
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References
• 1- Hench LL. The story of bioglass. J Mater Sci Mater Med 2006;17 (11):967–978
• 2- Ferreira MM, Brito AF, Brazete D, et al; Experimental Study in Rats. Doping β-TCP as a
strategy for enhancing the regenerative potential of composite β-TCP-alkali-free bioactive
glass bone grafts. Materials (Basel) 2018;12(01):4.
• 3- Hench LL, Splinter RJ, Allen WC, Greenlee TK. Bonding mechanisms at the interface of
ceramic prosthetic materials. J Biomed Mater Res Symp 1971;5(06):117–141
• 4- Skallevold HE, Rokaya D, Khurshid Z, Zafar MS. Bioactive glass applications in dentistry. Int J
Mol Sci 2019;20(23):5960.
• 5- Rodriguez O, Alhalawani A, Arshad S, Towler MR. Rapidly-dissolving silver-containing
bioactive glasses for cariostatic applications. J Funct Biomater 2018;9(02):28.
• 6- Jones J, Gentleman E, Polak J. Bioactive glass scaffolds for bone regeneration. Elements.
2007;3:393–399
• 7- Hoppe A, Jokic B, Janackovic D, et al. Cobalt-releasing 1393 bioactive glass-derived
scaffolds for bone tissue engineering applications. ACS Appl Mater Interfaces
2014;6(04):2865–2877
• 8- Groh D, Döhler F, Brauer DS. Bioactive glasses with improved processing. Part 1. Thermal
properties, ion release and apatite formation. Acta Biomater 2014;10(10):4465–4473
• 9- El-Meliegy E, Noort R. Glasses and Glass Ceramics for Medical Applications. New York, NY:
Springer; 2012
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Thanks

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