Bioactivity in the Field of Dentistry

Categories: Restorative Dentistry

Author(s): Christopher Canizares DMD

Date: 05-07-2020 14:24:58 pm

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Bioactive materials have long been used in medicine. Since the invention of 45S5 Bioglass by Dr. Larry Hench, they have evolved and taken on many applications. Before the invention of Bioglass, biomaterials were generally meant to be inert when in contact with body fluids and anatomical structures; however, 45S5 Bioglass changed the game by providing an alternative to graft materials that was active and bonded to bone and released biologically active ions to promote osteogenesis.1 Since then, biocompatibility has evolved to include second-generation materials that can elicit a controlled action/reaction in a biological setting and third-generation materials that stimulate a cellular response at a microbiological level.2 Fourth-generation biomaterials are aiming to use bioelectricity to alter signals to regenerate tissue, monitor cellular responses, and allow for communication with host tissues.3

After its creation in the late 1960s, 45S5 Bioglass found an array of applications in medicine and dentistry. Its first clinical implant application in the United States was to replace bones in the middle of the ear to treat hearing loss and was marketed under the names “Bioglass Ossicular Reconstruction Prosthesis” or “Middle Ear Prosthesis.”1 Not long after, Bioglass found its way into dentistry. Its first commercial dental application was the endosseous ridge maintenance implant. This device, marketed in 1988, was used to replace the roots of teeth after extraction and provide support for prosthetic replacements such as dentures.1 This advancement eventually led to the development of products such as PerioGlas (used to repair bone defects in the jaw and help regenerate bone around a tooth root) and NovaBone (used not only to repair bone defects in the jaw, but also for orthopedic applications in certain sites).1 Over the past decades, these materials have found more acceptance in both fields. Medical applications included everything from skeletal muscle repairs to aiding in cancer treatments; dental use expanded from bone regeneration to remineralization of tooth structures, decreased dental hypersensitivity, and improved cements.

Since its Food and Drug Administration approval in 1985 until 2016, Hench’s original 45S5 Bioglass is estimated to have been implanted in 1.5 million patients to restore bone and repair dental defects.1
This article will focus on dental use of bioactive glasses (and bioactive materials in general) and how these products can positively impact patient care.

Fluoride-releasing Materials

The concept of bioactivity in dentistry has been around for decades. One of the earliest forms can be found in ion-releasing compounds to aid enamel remineralization and prevent primary and secondary caries. One ion shown to have this effect is fluoride. When fermentable sugars are found in the mouth, bacteria in plaque metabolize these sugars, resulting in byproducts (particularly lactic acid) that can break down hydroxyapatite and increase demineralization.4 This throws off the balance of demineralization/remineralization in favor of the former, resulting in tooth decay. Fluoride induces remineralization and promotes the mineral phase of the tooth, inhibiting tooth decay.4 It is no wonder this ion has found its place in various dental products and is the focus of many clinical trials and studies.

One application in which fluoride-releasing materials have been extensively investigated is sealants and their contribution to dental caries prevention, with many studies showing promising results. For example, in a study by Lobo et al, investigators evaluated sealants and their effect on enamel demineralization, with a focus on physical protection by the sealant and the effects of fluoride on neighboring enamel. This study, conducted at the Piracicaba School of Dentistry in São Paulo, Brazil, consisted of taking 48 impacted, caries-free human third molars and randomly allocating them into four groups: no sealant (control), resin modified glass ionomer (RMGI) sealant, fluoride-releasing composite sealant (FRCS), and nonfluoridated composite sealant (NFCS).5 An area of the occlusal surface 3 mm long x 4 mm wide (with the central groove in the center) and a square window 4 mm x 4 mm on the buccal were outlined on each tooth. Each sealant group was then subjected to a five-day pH cycling regimen to mimic a high caries environment, while the control group was kept in a stable, moist environment at 37° C. The following variables were then evaluated: fluoride uptake in the buccal window, fluoride release by the sealant, and cross-sectional microhardness.

This study found that the RMGI sealant group exhibited higher levels of fluoride release, greater uptake by neighboring enamel, and diminished demineralization, while the FRCS group showed reduced demineralization on unsealed enamel and delivered fluoride uptake in areas of enamel away from the sealant.5 The authors postulate that the lack of demineralization on sealed enamel, regardless of material used, was a testament to the protection created by the “physical barrier” provided by the sealant, while demineralization reduction in areas of enamel surrounding RMGI was a result of its superior fluoride-releasing capability.5

Despite findings showing the effectiveness of fluoride-releasing sealants, several studies have shown conflicting results. For example, a systematic review and meta-analysis conducted by Alirezaei, Bagherian, and Sarraf Shirazi failed to show this purported benefit. In this review, the investigators performed a search of PubMed, Scopus, Embase, the Cochrane Library, and the Scientific Information Web of Knowledge using the same key search words. They performed their final search on September 20, 2017, and did not have time or language exclusions. Two investigators, both in the field of pediatric dentistry, independently reviewed/selected articles, and in the case of a disagreement, a third-party reviewer was brought in if necessary. After initially finding 2,411 studies, the authors removed studies that did not fit the desired criteria and ultimately included 31 studies—16 with a low risk of bias and the remaining 15 with a medium risk.6 The investigators completed two independent analyses of the included studies and found no difference in the percentage of caries formation when using glass ionomer cements (fluoride-releasing) compared to resin-based sealants (nonfluoride-releasing); however, they did find a higher retention rate favoring resin-based sealants.6

The use of fluoride-releasing materials in dentistry is not exclusive to sealants; they are commonly used as cements, buildup materials, and permanent restorations (cervical restorations in particular). For instance, glass ionomers can be used as restorations, particularly in pediatric dentistry and when employing the atraumatic restorative treatment technique.4 These materials are calcium or strontium fluoro aluminosilicate glass powder–based and can release ions such as fluoride, calcium, and phosphate.4 Fluoride release by these materials is not only immediate, but also has been shown to last for up to several years. In fact, these compounds can undergo “fluoride recharge” and take up fluoride ions under certain conditions, such as by exposure to other fluoridated substances, which may contribute to their long-term effectiveness.7 The ions released by glass ionomers form sturdy bonds with tooth structure; however, these types of restorations generally are not as esthetic as other available restorative materials, and thus are not commonly used for restoring permanent dentition.4

RMGIs combine the bioactive properties of glass ionomer with a more esthetic restorative result. They are similar to glass ionomer in that they form adhesive bonds to enamel and dentin while releasing fluoride, but possess the organic monomer 2-hydroxyethyl methacrylate (HEMA),8 which allows for greater strength of the set material. However, if not cured properly, RMGIs release increased amounts of unpolymerized HEMA and negatively impact biocompatibility by diffusing through dentin and potentially adversely affecting the pulp. Clinicians should always follow manufacturer curing time guidelines.Dental professionals also should be careful when handling materials with HEMA because exposure to unprotected skin can lead to allergic reactions.8 However, when Nicholson and Czarnecka reviewed the biocompatibility of RMGI cements for dentistry, they found that despite the potential hazard to dental personnel, “no reports” appear in the available literature (as of the date of publication) of “acrylate allergy” linked to the specific use of RMGIs.<span class=">8 Giomers are another material option with ion-releasing abilities. These materials are similar to flowable composite but contain prereacted glass ionomer as part of their filler.4,9 As with glass ionomers and RMGIs, giomers contain both fluoride-release and recharge capabilities, but also have the added advantages of superior esthetics, strength comparable to resin, and improved polishability.9 Giomer fluoride release also has been linked to antibacterial properties.4 These materials release ions such as sodium, borate, and aluminum; however, they do not release calcium or phosphate ions and are unable to form hydroxyapatite to assist in tooth structure regeneration.

Regardless of the often-ambiguous findings on the extent of fluoride release and reuptake by varying bioactive materials, fluoride can aid enamel remineralization and prevent caries. More studies are needed to assess the true effectiveness of ion-releasing biomaterials on dentition. As the physical attributes and capabilities of materials improve, the desired results may become more evident. For example, the use of RMGIs and even fluoride-releasing composites have helped address retention shortcomings experienced by previously used sealants while adding the purported benefit of fluoride release.5

Calcium-based Materials

Various dental biomaterials use different compounds as the basis for their respective bioactivity. For instance, many bioactive materials are either calcium silicate– or calcium aluminate– based. Calcium silicate cements came on the dental scene as a root restoration material used

in endodontic therapy, the first of which was mineral trioxide aggregate (MTA).10 This material is similar to Portland cement, which is a common type of cement and a basic ingredient of concrete and stucco. MTA consists of tricalcium and dicalcium silicates and was seen as an attractive dental material because of its hydraulic nature; endodontic restorative materials need to be effective in a wet environment.10 Bismuth oxide was added to MTA to provide radiopacity, allowing clinicians to see it in radiographs.

MTA has been shown to exhibit antifungal and antibacterial activity (purportedly due to its alkaline pH), and some studies have found that calcium hydroxide formation and deposition of a hydroxyapatite-like substance contribute to its biocompatibility.10 Due to these favorable attributes, MTA has found dental applications other than root end replacement. It has been used as a root canal sealer, pulp capping material, pulpotomy dressing, and during apexification of developing teeth.10 Other variations of calcium silicate–based biomaterials (for example,

BioAggregate) lack calcium aluminate, have added components such as hydroxyapatite, and show antibacterial characteristics similar to MTA.10 Tricalcium silicate–based materials (for example, Biodentine) offer the biocompatibility of MTA but have a faster set time that allows for more clinical indications, such as restoring large coronal or cervical caries, in addition to typical MTA indications.10

Calcium aluminate-based biomaterials also have been used in dentistry due to their bioactive properties. Examples of such materials include a hybrid luting cement, direct restorative cement,and use in endodontic treatment similar to MTA.11 Like its calcium silicate-based counterparts, this material mainly is used in construction but has gained popularity in dentistry, and some research has found that it possesses physical properties, such as microhardness and compressive strengths, that may be superior to MTA.11 Evidence exists demonstrating its ability to form hydroxyapatite. Lööf et al. conducted an in vitro study to compare the bioactivity of two calcium aluminate cements (one in which calcium was the only active substance; the other a hybrid with a glass ionomer) with a traditional glass ionomer cement.12 In this study, the three materials were submerged in a phosphate-buffered saline at 37° C for the following amounts of time: 1 hour, 1 day, 7 days, and 4 weeks. The saline was changed on a weekly basis, and samples were removed from the solution at their designated time, at which point they were rinsed with distilled water and stored in a desiccator for at least 7 days before analysis. The samples were then analyzed by grazing incidence x-ray diffraction, a transmission electron microscope, a scanning electron microscope, and energy dispersive spectroscopy. The investigators found that the calcium-based cement demonstrated bioactivity by formation of hydroxyapatite on its surface, with its detection taking only 24 hours. The hybrid cement also displayed bioactivity, but hydroxyapatite formation was detected after 7 days. No bioactivity was detected with the glass ionomer control.12

Bioactive Glasses in Restorations

At the beginning of this article some potential dental applications of Bioglass and other bioactive glasses were discussed. It should be no surprise that modern restorative dentistry is seeing a trend of incorporating bioactive glass into its restorations and cements as well. Although different compositions and structures of glass result in varying properties, bioactive glasses generally exhibit bioactivity by not only forming bone-like apatite layers in physiologic environments, but also by stimulating bone formation.13 Bioactive glasses are known to cause calcium phosphate precipitations, and studies have suggested that they can be used to remineralize damaged dentin.13 For instance, in a study by Prabhakar et al., investigators added bioactive glass to glass ionomer and RMGI cements to examine its effect on demineralized dentin. Eighty caries- and restoration-free permanent mandibular premolars were obtained, and standardized Class V preparations were made on the buccal and lingual surfaces of each tooth. The teeth were then split into 4 groups of 20 teeth each and exposed to pH cycling to mimic carious conditions. The teeth were then sectioned, prepared, and restored with their respective materials. The remineralization and microhardness were evaluated by means of an imaging system (as described for demineralization) and a microhardness tester, respectively.13 The results of this study showed that adding bioactive glass to the glass ionomer and RMGI cements resulted in “significant remineralization,” with the RMGI hybrid not only showing the highest bioactivity and remineralization, but also a calcium phosphate–like precipitation on the specimen surface.13 Although the addition of bioactive glass to the glass ionomer cement had a positive effect in the form of remineralization, it compromised the surface hardness, but only to a limited extent.

Materials that contribute to remineralization can have broad dental applications. For instance, in addition to their proposed use as restorative materials, bioactive glasses are being investigated to battle white spot lesions during orthodontic treatment because of their remineralization capabilities. In addition, bioactive glasses have demonstrated antimicrobial characteristics (presumably due to their alkalinity), with no discovered resistance.14 Also, bioactive glasses have the potential to aid in reducing tooth sensitivity by occluding dentinal tubules via hydroxyapatite deposition and binding to collagen fibers.14 These capabilities make bioactive glass materials particularly interesting not only as a restorative option, but also for their potential in everything from teeth whitening to endodontic treatment to implant dentistry.

Conclusion

The concept of bioactivity has been present in healthcare for decades and does not appear to be going anywhere soon. In fact, its presence will likely be felt more as time goes on. As technology advances, so do biomaterials. Clinical studies and research will lead the way in creating products that will not only integrate with anatomical structures but also help them further regenerate. From fluoride release to the development and evolution of bioactive glasses, the field of dentistry seems poised to benefit from this expansion and growth. With indications in nearly every dental specialty, bioactive materials may in fact become the new norm in modern dentistry.

 References

1.    Baino F, Hamzehlou S, Kargozar S. Bioactive glasses: Where are we and where are we going? J Funct Biomater. 2018;9(1):25.

2.    Hench LL, Polak JM. Third-generation biomedical materials. Science. 2002;295(5557):1014-17.

3.    Ning C, Zhou L, Tan G. Fourth-generation biomedical materials. Materials Today. 2016;19(1):2-3.

4.    Nicholson J. Fluoride-releasing dental restorative materials: An update. Balk J Dent Med. 2014;18(2):60-9.

5.    Lobo MM, Pecharki GD, Tengan C, et al. Fluoride-releasing capacity and cariostatic effect provided by sealants. J Oral Sci. 2005;47(1):35-41.

6.    Alirezaei M, Bagherian A, Sarraf Shirazi A. Glass ionomer cements as fissure sealing materials: Yes or no? A systematic review and meta-analysis. J Am Dent Assoc. 2018;149(7):640-9.

7.    Bayrak S, Tunc ES, Aksoy A, et al. Fluoride release and recharge from different material used as fissure sealants. Eur J Dent. 2010;4(3):245-50.

8.    Nicholson JW, Czarnecka B. The biocompatibility of resin-modified glass-ionomer cements for dentistry. Dent Mater. 2008;24(12):1702-8.

9.    Kimyai S, Savadi Oskoee S, Ajami AA, Sadr A, Asdagh S. Effect of three prophylaxis methods on surface roughness of giomer. Med Oral Patol Oral Cir Bucal. 2011;16(1):e110-4.

10.  Jefferies SR. Bioactive and biomimetic restorative materials: A comprehensive review. Part 1. J Esthet Restor Dent. 2014;26(1):14-26.

11.  Garcia L. Calcium aluminate based-cements for endodontic application. JJ Dent Res. 2014;1(2):008.

12.  Lööf J, Svahn F, Jarmar T, et al. A comparative study of the bioactivity of three materials for dental applications. Dent Mater. 2008;24(5):653-9.

13.  Prabhakar AR, Jibi Paul M, Basappa N. Comparative evaluation of the remineralizing effects and surface microhardness of glass ionomer cements containing bioactive glass (S53P4): An in vitro study. Int J Clin Pediatr Dent. 2010;3(2):69-77.

14.  Skallevold HE, Rokaya D, Khurshid Z, Zafar MS. Bioactive glass applications in dentistry. Int J Mol Sci. 2019;20(23):5960.

 

About the Author

Christopher Canizares, DMD

Christopher Canizares is currently practicing orthodontics in Rome, New York. He completed his specialty training at NYU Langone Health’s Advanced Education Program in Orthodontics and Dentofacial Orthopedics. He received his DMD from Boston University Henry M. Goldman School of Dental Medicine and completed a General Practice Residency at Montefiore Medical Center before practicing general dentistry for 5 years.

 

Dr. Canizares can be reached at canizares.christopher@gmail.com