Year : 2016 | Volume
: 7 | Issue : 1 | Page : 27--32
Bioactive glass: A potential next generation biomaterial
Srishti Sarin1, Amit Rekhi2,
1 Department of Public Health Dentistry, Sudha Rustagi College of Dental Sciences and Research, Faridabad, Haryana, India
2 Department of Public Health Dentistry, Uttaranchal Dental and Medical Research Institute, Mazri Grant, Dehradun, Uttarakhand, India
Department of Public Health Dentistry, Uttaranchal Dental and Medical Research Institute, Mazri Grant, Haridwar Road, Dehradun, Uttarakhand
Historically the function of biomaterials has been to replace diseased or damaged tissues. The first generation biomaterials were selected to be as bio-inert as possible and thereby minimize formation of scar tissue at the interface with host tissues. Bioactive glasses (BAGs) were discovered in 1969 and provided for the first time an alternative; the second generation, interfacial bonding of an implant with host tissues. Tissue regeneration and repair using the gene activation properties of Bioglass® provide a third generation of biomaterials. This article reviews the history of the development of BAGs, with emphasis on the first composition, 45S5 Bioglass®, that has been in clinical use since 1985. A bioactive ceramic is a ceramic that generate a positive reaction in the biological environment of the implants and/or chemical reaction that modify the material in a certain thickness under the surface.
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Sarin S, Rekhi A. Bioactive glass: A potential next generation biomaterial.SRM J Res Dent Sci 2016;7:27-32
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Sarin S, Rekhi A. Bioactive glass: A potential next generation biomaterial. SRM J Res Dent Sci [serial online] 2016 [cited 2019 Dec 5 ];7:27-32
Available from: http://www.srmjrds.in/text.asp?2016/7/1/27/176482
Bioactive materials are durable materials that can bind chemically with the surrounding bones and in some cases even with soft tissue. When bioactive materials are implanted in the body, a porous biologically active layer is formed that is a very favorable substrate for the regrowth of bone tissue. The material is ideal as bone cement filler and coating because of its biological activity. A bioactive ceramic is a ceramic that generate a positive reaction in the biological environment of the implants and/or chemical reaction that modify the material in a certain thickness under the surface.
The bioactive ceramic are divided into two classes:
Ceramics that induct bioactivity due to their chemical compositionCeramics in which the bioactivity is induced or by superficial treatment or by filling of the porosity by pharmacological active substance.
The bioactive ceramics are:
Bioactive glass (BAG) (Bioglass ®, Ceravital ®)BAG-ceramics (A/W glass-ceramic, dense and porous hydroxyapatite).
History of Bioactive Glass
Hench et al., 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. Hench et al., summarized the bone bonding strength of bioglass in a review article in 1982.
A quantitative evaluation of interfacial shear strength in rat and monkey models showed that the strength of the interfacial bond between Bioglass ® and cortical bone was equal to or greater than the strength of the host bone.,,
Weinstein et al., published a key paper describing the biomechanics of the bonded interface.
In 1977, a BAG-ceramic based upon the 45S5 Bioglass ® formula with small additions of K2O and MgO, trademarked Ceravital, was implanted in animal models by Professor Ulrich Gross and colleagues at the Free University of Berlin. They found that the glass-ceramic bonded to bone with a mechanically strong interface.,
Properties of Bioactive Glass
BAGs, as opposed to most technical glasses, are characterized by the materials' reactivity in water and in aqueous liquids. The bioactivity of BAGs is derived from their reactions with tissue fluids, resulting in the formation of a hydroxycarbonate apatite (HCA) layer on the glass.
When BAGs are brought into contact with body fluids a rapid leach of Na + and congruent dissolution of Ca 2+, PO4,3− and Si 4+ takes place at the glass surface. A polycondensated silica-rich (Si-gel) layer is formed on the glass bulk, which then serves as a template for the formation of a calcium phosphate (Ca/P) layer at its outer surface. Eventually, the Ca/P crystallizes into HCA, the composition of which corresponds to that of bone. Because of this phenomenon and their good biocompatibility, BAGs were introduced in dentistry: As substitutes for reconstruction of voids and defects of facial bones,,, in rehabilitation of the dentoalveolar complex, including BAG implants  and regeneration of periodontal bone support.,,
Recently, evidence has emerged suggesting that certain compositions of BAGs create an osteoconductive response; aid in the differentiation of osteoprogenitor cells to osteoblasts and enhance bone proliferation. The essential chemical property of BAGs to release Si +, Ca,2+ and PO43− in the tissue fluid, resulting in the initiation of apatite formation on the glass surface has led us to believe that it might also be quite possible to use the materials as vehicles for ectopic mineralization of the surrounding tissue. In this case, the BAGs may have therapeutic value as mineralizing agents in caries prophylactics, and also as a desensitizing agent in clinical situations where opened dentinal tubules lead to hypersensitive teeth.
Furthermore, in implantology, a coating of technically adequate BAG on the fixture surface may serve as a means to attach mucosal or dermal soft tissues to the osseointegrated construction by an HCA bridge., In addition, BAGs may also have an application in root canal therapy providing a biological seal in the form of mineral deposition inducing materials in the root canal and at the apex. This in vitro study was designed to find out whether BAG S53P4 can be used to induce mineralization in living connective tissue, in decalcified dentin matrix and in natural dentin with opened dentinal tubules.
The BAGs can be employed to repair and to rebuild damaged tissues, particularly hard tissues. One point that differentiates them from other bioactive ceramics or glass-ceramic is the possibility to tailor a great chemical range of properties and of linking speed to the tissues. Therefore, it is possible to design glasses with tailored property for a specific clinical application.
The BAGs can be produced with the conventional technologies of the glass industry, but it is necessary to verify the purity of the raw materials, to avoid the contamination of impurity and the loss of volatile elements, like Na2O, or P2O5. The different phases of production, so like the choice of the raw materials, influence the final features of the piece. The BAGs are soft glasses and, therefore, the final shape can be easily given with conventional tools.
The base components are usually SiO2, Na2O, CaO, and P2O5 and given below are percentages in weight of the most common BAGs.
Bioglass composition in wt%
SiO2-45 wt%Na2O - 24.5 wt%CaO - 24.5 wt%P2O5-6 wt%.
The most studied is the Bioglass ® 45S5. The abbreviation indicates that it contains 45% in weight of SiO2(oxide creator) and the molar rate between Ca/P is of 5:1. Glasses with significantly lower molar rate (in the form of CaO and P2O5) do not generate connections with the bone.
Advantages and Disadvantages of Bioactive Glass
The main advantage of the BAGs is the high superficial speed reaction that brings to rapid connections to the tissues. The greater disadvantages are the not optimal mechanical property and the meagre break resistance. The out bending-tensile rigidity of the greater part of the BAGs varied between 40 and 60 MPa, and they are not, therefore, usable for loading applications. Bioglasses are embedded in a biomaterial support to form prosthetics for hard tissues. Such prosthetics are biocompatible, show excellent mechanical properties and are useful for orthopedic and dental prosthetics.
The elastic modulus is in the order of 30–35 GPa, and it is very similar to that of the cortical bone. The low resistance does not hinder the use of the BAGs like covering, where the limiting factor is the resistance of the interface between the metal and the covering, so it does not hinder the use in low load or loaded in compression implantations, in shape of dust, or like bioactive phase in composites.
Mechanism of Bioactivity
Stage 1: It is the loss of sodium ions (Na +) from the surface of the glass via ion exchange with hydrogen (H + or H3O +). This reaction occurs very rapidly, within minutes of material exposure to bodily fluids, and creates a de-alkalinization of the surface layer with a net negative surface charge. This stage is usually controlled by diffusion and exhibits a t −1/2 dependence.
Stage 2: Loss of soluble silica in the form of Si (OH)4 to the solution resulting from the breaking of Si-O-Si bonds and formation of Si-OH (silanols) at the glass solution interface.
This stage is usually controlled by interfacial reaction and exhibits a t 1.0 dependence. Hench has proposed that the loss of soluble silica from the surface of BAGs might be at least partially responsible for stimulating the proliferation of bone-forming cells in the area of the glass surface.
Stage 3: Condensation and repolymerization of a SiO2-rich layer on the surface depleted in alkalis and alkaline earth cations.
Stage 4: Migration of Ca 2+ and PO43− groups to the surface through the SiO2-rich layer forming a CaO-P2O5-rich film on top of the SiO2-rich layer, followed by growth of the amorphous CaO-P2O5-rich film by incorporation of soluble calcium and phosphates from solution.
Stage 5: Crystallization of the amorphous CaO-P2O5 film by incorporation of OH −, CO32−, or F − anions from solution to form a mixed hydroxyl, carbonate, fluorapatite layer.
The adsorption of proteins and other biologic moieties occurs concurrently with the first four reaction stages and is believed to contribute to the biological nature of the HCA layer. Within approximately 3-6 hrs in vitro, this Ca/P layer will crystallize into the HCA layer. Because this surface is chemically and structurally nearly identical to natural bone mineral, the body's tissues are able to attach directly to it. As the reactivity continues, this surface HCA layer grows in thickness to form a bonding zone of 100–150 µm – A mechanically compliant interface that is essential for maintaining the bioactive bonding of the implant to the natural tissue. These surface reactions occur within the first 12–24 h of implantation.
Thus by the time osteogenic cells, such as osteoblasts or mesenchymal stem cells, infiltrate a bony defect–which normally takes 24–72 hours–they will encounter a bonelike surface, complete with organic components, and not a foreign material.
Stage 6: Adsorption of biological moieties in the SiO2-hydroxycabonate apatite layer.
Stage 7: Action of macrophages.
Stage 8: Attachment of stem cells.
Stage 9: Differentiation of stem cells.
Stage 10: Generation of matrix.
Stage 11: Mineralization of matrix.
It is this sequence of events, in which the BAG participates in the repair process that allows for the creation of a direct bond of the material to tissue. The body's normal healing and regeneration processes (stages 7–11) begin after these surface layers have begun to form. BAGs appear to minimize the duration of the macrophage and inflammatory responses that accompany any trauma, including surgery.
Implication of Bioactive Glass in Dentistry
BAG is used extensively in medicine and dentistry. The first Bioglass ® device cleared for marketing in the United States was a device used to treat conductive hearing loss by replacing the bones of the middle ear. The device was called the “Bioglass ® Ossicular Reconstruction Prosthesis,” and trade named “MEP ®.” It was a solid, cast Bioglass ® structure that acted to conduct sound from the tympanic membrane to the cochlea. The advantage of the MEP ® over other devices in use at the time was its ability to bond with soft tissue (tympanic membrane), as well as bone tissue. The second Bioglass device to be placed into the market was the Endosseous Ridge Maintenance Implant ®, in November 1988. The device was designed to support labial and lingual plates in natural tooth roots and to provide a more stable ridge for denture construction following tooth extraction. The devices were simple cones of 45S5 Bioglass ® that were placed into fresh tooth extraction sites. They bonded to the bone tissue and proved to be extremely stable, with much lower failure rates than other materials that had been used for that same purpose.
When the glass composition exceeds 52% by weight of SiO2, the glass will bond to the bone but not to soft tissues. This finding provided the basis for clinical use of Bioglass ® in ossicular replacement and also for implants to maintain the alveolar ridge of edentulous patients. Subbaiah and Thomas  carried out a clinical study to evaluate the efficacy of a bioactive alloplast, Perioglas in comparison with open flap debridement only in the treatment of periodontal osseous defects showed that radiographically BAG group showed significant improvement in bone fill over the sites treated with open debridement alone. This indicates that alloplastic bone graft material, Perioglas demonstrated clinical advantages beyond that achieved by debridement alone. BAG is used extensively in dentistry in the treatment of bone defects, ridge preservation, and periodontal bone defects.
Nanoparticles range from 1 nm to100 nm in size and consist of physiochemical property that does not exhibit in a bulk form where the materials display constant physical properties apart from their size. Nanoparticles hold large surface area to volume ratio which shows high binding capacity and have the potential to easily conjugate with biomolecules. BAG polymer nanocomposites are a relatively new class of bioactive materials that are suitable primarily for applications as orthopedic three-dimensional (3D) scaffolds or as bone filler materials that combine important mechanical properties and bioactivity with a polymer's great flexibility and capacity to deform under loads. Nanostructured bioglass-based materials have been created in the form of 3D scaffolds, as nanoparticles, or coatings which show comparable mechanical properties to those of natural bone. These have been created by various methods such as by sol-gel processing, unidirectional freezing of suspensions, solid freeform fabrication, electrospinning, polymer foam replication, microemulsion techniques, and others. These products have the potential of enhanced bioactivity because of the increased specific area which leads to faster dissolution and release of ions, and a higher protein adsorption.,
Tai et al., conducted a study with the objective to evaluate the antigingivitis and antiplaque effect of a dentifrices containing BAG (NovaMin ®) particulate compared with a placebo control dentifrices in a 6 weeks clinical study, results showed that dentifrices containing NovaMin significantly improves the oral health as measured by reduction in gingival bleeding and reduction in supragingival plaque. When exposed to an aqueous medium, a sort of dissolution takes place where sodium ions in particles begin to exchange with hydrogen cations and this rapid process allows the calcium and phosphate ions to be released. A localized, transient increase in pH occurs during an initial exposure of the material due to the release of sodium. This increase in pH helps to precipitate the calcium and phosphate ions from the NovaMin ® particle, along with the calcium and phosphorus found in saliva, to form a Ca/P layer which crystallizes into HCA, which is chemically and structurally equivalent to biological apatite.
Mengel et al., conducted a clinical and a radiological study to compare the long-term effectiveness of a bioabsorbable membrane and a BAG in the treatment of intrabony defects in patients with generalized aggressive periodontitis, results showing significant improvement in probing depth and clinical attachment loss. Radiographically, the defects were found to be filled significantly more in BAG group.
BAG particles ranging between 300 and 355 mm in diameter (BioGran) have shown in animal experiments to possess bone regenerative activities. For this reason, the material has also been used for repair of alveolar bone defects in humans  and recently it has been used for sinus floor augmentation in humans, showing bone regenerative activity.
Aitasalo et al., concluded in his study that BAG implant is a well-documented material in orbital floor reconstruction. It provides a favorable environment for an uncomplicated healing process because it is bioactive and biocompatible and causes new bone formation.
BAGs are silicates containing sodium, calcium, and phosphate as their main components. They bind to the bone by a surface layer of hydroxylapatite that forms through a chemical reaction with the glass. This chemical bonding of BAG and bone has been shown by several investigators., BAG is biocompatible, bone-bonding, and osteoconductive in humans. Good results have been achieved with this material in frontal sinus surgery.,
Bioglass is not only bioactive, but it is also bacteriostatic, which may be one reason why there were no acute or late infections after frontal sinus obliteration or orbital floor reconstruction. BAG is considered to be a breakthrough in re-mineralization technology. This is because the current standard treatment for tooth remineralization and prevention of decay is slow acting and is dependent on adequate saliva as a source of calcium and phosphorus., When BAG is incorporated into toothpaste formulations, the ions released from the amorphous Ca/P layer are believed to contribute to the remineralization process of the tooth surface.
Recently, it has been demonstrated that fine particulate BAGs (<90 um) incorporated into an aqueous dentifrice have the ability to clinically reduce the tooth hypersensitivity through the occlusion of dentinal tubules by the formation of the carbonated hydroxyapatite layer.
BAGs of the SiO2-Na2O-CaO-P2O5 type have recently been suggested as topical root canal disinfectants.
Similarly to calcium hydroxide, the most frequently advocated interappointment dressing, BAGs disinfect their environment viathe continuous release of alkaline species in a wet environment. Calcium hydroxide and also BAG suspensions are best administered as slurries that can be applied by means of a counter angle handpiece and a lentulo spiral. However, in contrast to calcium hydroxide, BAGs do not weaken the dentin structure. They release calcium, phosphate, sodium, and silica, and thus change slowly into pure inert Ca/P particles.
BAGs cause Ca/P precipitation in their environment. Consequently, these materials transform from reactive local antiseptics into a bioactive hard tissue like structure over time. Investigators have demonstrated a significant antimicrobial effect against caries pathogens (Streptococcus mutans, Streptococcus sanguinis) upon exposure to BAG powders, as well as solution and extracts.,,
BAG has emerged as a versatile material in the recent past and as it is available in multiple forms which can be molded desirably as per the need of the user. Modern approaches implicate the use of biomaterials that can actively interact with tissue and induce their intrinsic repair and regenerative potential. While silicate based BAGs have been widely investigated over the last decades, borate and borosilicate compositions are now providing new opportunities for the application of BAG in tissue engineering with concerns about the toxicity of borate glasses decreasing after successful animal studies.
The ability of BAG to support osteogenesis is well known but recent work has also shown its proangiogenic potential, which should provide benefits for the application of BAG to soft tissue repair which are being seen in recent works regarding the tissue-engineered regeneration of structures such as the synovial joint condyle, bone tendon complex, bone ligament junction, and the periodontium. Controlled delivery of bioactive agents, such as anti-inflammatory drug or proteins that promote different biological events is another area where these particles are being looked into. A strong investment in the exploitation of grafting of different peptides, antibodies, and proteins which are able to induce stem cell recruitment, proliferation, and differentiation is expected.
The potential of these materials for remineralization of both enamel and dentin has been studied in vitro and in situ and holds promise. In addition, the unique ionic reactions and potential antimicrobial and anti-inflammatory properties might prove useful in treating gingivitis. Bioactive material is also being isolated from natural sources like plants, animals, and microbes and show promise in the application in various fields such as malaria, cancer, heart disease, drug delivery, and diagnosis.
However, it should be noted that most of the supporting data have been overwhelming from in vitro studies and hence further longitudinal studies are necessary to look into the human based interaction. Future research will look to limit the effects of its brittleness through innovative scaffold design and processing, particularly when applied to the repair of load-bearing bones. With newer research going on currently, the scope of BAG is bound to increase manifold.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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