Trends and perspectives on the commercialization of bioactive glasses.

At least 25 bioactive glass (BG) medical devices have been approved for clinical use by global regulatory agencies. Diverse applications include monolithic implants, bone void fillers, dentin hypersensitivity agents, wound dressing, and cancer therapeutics. The morphology and delivery systems of bioactive glasses have evolved dramatically since the first devices based on 45S5 Bioglass®. The particle size of these devices has generally decreased with the evolution of bioactive glass technology but primarily lies in the micron size range. Morphologies have progressed from glass monoliths to granules, putties, and cements, allowing medical professionals greater flexibility and control. Compositions of these commercial materials have primarily relied on silicate-based systems with varying concentrations of sodium, calcium, and phosphorus. Furthermore, therapeutic ions have been investigated and show promise for greater control of biological stimulation of genetic processes and increased bioactivity. Some commercial products have exploited the borate and phosphate-based compositions for soft tissue repair/regeneration. Mesoporous BGs also promise anticancer therapies due to their ability to deliver drugs in combination with radiotherapy, photothermal therapy, and magnetic hyperthermia. The objective of this article is to critically discuss all clinically approved bioactive glass products. Understanding essential regulatory standards and rules for production is presented through a review of the commercialization process. The future of bioactive glasses, their promising applications, and the challenges are outlined. STATEMENT OF SIGNIFICANCE: Bioactive glasses have evolved into a wide range of products used to treat various medical conditions. They are non-equilibrium, non-crystalline materials that have been designed to induce specific biological activity. They can bond to bone and soft tissues and contribute to their regeneration. They are promising in combating pathogens and malignancies by delivering drugs, inorganic therapeutic ions, and heat for magnetic-induced hyperthermia or laser-induced phototherapy. This review addresses each bioactive glass product approved by regulatory agencies for clinical use. A review of the commercialization process is also provided with insight into critical regulatory standards and guidelines for manufacturing. Finally, a critical evaluation of the future of bioactive glass development, applications, and challenges are discussed.

The effect of bioactive glasses on enamel remineralization: A systematic review.

INTRODUCTION/OBJECTIVES: To evaluate the effectiveness of bioactive glasses in promoting enamel remineralization. DATA: An electronic search with a complementary gray literature search for in vivo and in vitro research. No language restrictions were applied. SOURCES: MEDLINE and EMBASE via OVID, the Cochrane Oral Health Group's Trials Register, CENTRAL and LILACS STUDY SELECTION: One hundred and sixteen studies were identified, of which, eleven met the inclusion criteria and formed the basis of this systematic review. Methodological quality was assessed independently by two reviewers. Factors investigated in the selected articles included the objective and subjective measures of enamel remineralisation; harms, including evidence of damage to the enamel surface; patient satisfaction; and in vitro evidence of enamel remineralisation, using recognized laboratory techniques. RESULTS: A total of 11 laboratory-based studies were included in this review. The methodological quality was deemed to be high in four, and medium in the remaining studies. Based on the in vitro studies, enamel remineralization improved with bioactive glasses, irrespective of the method of application. Ex vivo signs of remineralization such as increase in enamel hardness, the formation of an enamel-protective layer and reduced intensity of light backscattering were less evident with alternatives including fluoride, and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). CONCLUSIONS: Based on in vitro findings only, bioactive glasses may be capable of enhancing enamel remineralization in various formulations, compared with other topical remineralizing materials including fluoride, and CPP-ACP. However, clinical research to confirm their effectiveness is now overdue. CLINICAL SIGNIFICANCE: Bioactive glasses have potential utility in promoting enamel remineralization; however, clinical research exploring their clinical effectiveness is required.

Influence of cell culture medium composition on in vitro dissolution behavior of a fluoride-containing bioactive glass.

Bioactive glasses are used clinically for bone regeneration, and their bioactivity and cell compatibility are often characterized in vitro, using physiologically relevant test solutions. The aim of this study was to show the influence of varying medium characteristics (pH, composition, presence of proteins) on glass dissolution and apatite formation. The dissolution behavior of a fluoride-containing bioactive glass (BG) was investigated over a period of one week in Eagle's Minimal Essential Medium with Earle's Salts (MEM), supplemented with either, (a) acetate buffer, (b) 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, (c) HEPES + carbonate, or (d) HEPES + carbonate + fetal bovine serum. Results show pronounced differences in pH, ion release, and apatite formation over 1 week: Despite its acidic pH (pH 5.8 after BG immersion, as compared to pH 7.4-8.3 for HEPES-containing media), apatite formation was fastest in acetate buffered (HEPES-free) MEM. Presence of carbonate resulted in formation of calcite (calcium carbonate). Presence of serum proteins, on the other hand, delayed apatite formation significantly. These results confirm that the composition and properties of a tissue culture medium are important factors during in vitro experiments and need to be taken into consideration when interpreting results from dissolution or cell culture studies.

Influence of sodium content on the properties of bioactive glasses for use in air abrasion.

Air abrasion is used in minimally invasive dentistry for preparing cavities, while removing no or little sound dentine or enamel, and the use of bioactive glass (rather than alumina) as an abrasive could aid in tooth remineralization. Melt-derived bioactive glasses (SiO2-P2O5-CaO-CaF2-Na2O) with low sodium content (0 to 10 mol% Na2O in exchange for CaO) for increased hardness, high phosphate content for high bioactivity and fluoride content for release of fluoride and formation of fluorapatite were produced, and particles between 38 and 80 µm in size were used for cutting soda-lime silicate glass microscope slides and human enamel. Vickers hardness increased with decreasing Na2O content, owing to a more compact silicate network in low sodium content glasses, resulting in shorter cutting times. Cutting times using bioactive glass were significantly longer than using the alumina control (29 µm) when tested on microscope slides; however, glasses showed more comparable results when cutting human enamel. The bioactive glasses formed apatite in Tris buffer within 6 h, which was significantly faster than Bioglass® 45S5 (24 h), suggesting that the hardness of the glasses makes them suitable for air abrasion application, while their high bioactivity and fluoride content make them of interest for tooth remineralization.

A long-term study on the setting reaction of glass ionomer cements by (27)Al MAS-NMR spectroscopy.

OBJECTIVES: The main objective is the characterization of the setting reaction in glass ionomer cements (GICs) based on experimental glasses using the (27)Al magic angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy in order to understand the crosslinking process during the setting reaction. METHODS: Three types of GICs which are based on fluoro-alumino-silicate glasses (LG125, ART10, and LG26Sr) were studied using (27)Al MAS-NMR to monitor the setting reaction of the cements. RESULTS: The result showed clearly the formation of six coordinate, aluminium Al(VI), that crosslink the carboxyl groups in the PAA. The deconvolution study was performed to quantify the amount of each Al species in the cements. The finding showed that composition of original glass has a substantial effect on the setting behavior of the cements. SIGNIFICANCE: Our data demonstrate that the setting reaction of GICs can be followed by (27)Al MAS-NMR spectroscopy discovering the conversion of Al(IV) to Al(VI). Considerable amount of the five coordinate aluminium, Al(V), species was found in the cements aged up to one year. The presence of phosphorus has a strong influence on the setting reaction. The formation of Al-O-P species was postulated to be present in the cement.

Heat-pressed ionomer glass-ceramics. Part II. Mechanical property evaluation.

OBJECTIVES: A series of ionomer glasses based on the formula: 4.5SiO2-1.5P2O5-(X)Al2O3-4.5CaO-0.5CaF2, were investigated where X was varied from 3.0 to 1.5 in order to develop heat pressable dental ceramics. METHODS: The glasses were heat-pressed and then subjected to different heat-treatment cycles. The mechanical properties of the glass-ceramics were investigated, specimens were tested for hardness, fracture toughness (indentation method) and flexural strength (biaxial method). RESULTS: Good mechanical properties were obtained for heat-treatments at lower temperatures (i.e. 1150 degrees C). At intermediate heat-treatment temperatures the glass-ceramics were highly crystalline which did not favor the mechanical properties. There appears to be an inverse relationship between fracture toughness and flexural strength. High fracture toughness values of 2.7 (0.4) MPam0.5 were produced for the X = 2.8 glass heat-treated for 8 h at 1150 degrees C, the flexural strength was lowest for this heat-treatment. High flexural strengths of 194.4 (75.0) MPa were obtained by heat-treating the same glass for 1 h at 1150 degrees C. Increasing the hold time increases crystal size thereby increasing the extent of microcracking in the glass-ceramic thus lowering the flexural strength. Microcracks appear to increase the fracture toughness of the glass-ceramics probably by a crack termination mechanism. SIGNIFICANCE: Good flexural strength and high fracture toughness are attainable in this system, but appear to be mutually exclusive in the materials studied. With further investigation this system could provide clinically useful materials.