Abstract In 1969, fifty years ago, a young professor of ceramic engineering created a 4-component glass to be used as a bone replacement material. That material became known as “Bioglass” and more generally as a class of materials known as bioactive glass. Those first experiments conducted by Dr. Larry Hench completely shifted the paradigm of how the biomaterials and medical communities look at the interactions between inorganic materials and tissues in the body. This article will touch on just a few highlights of the development of bioactive glasses and relate those to the concepts of bioactivity and tissue bonding.

The terms “bioactive glass,” “bioactive ceramic,” “bioactive polymer,” and “bioactive metal” are common in the lexicon of the biomaterials scientist today. Each term is inherently understood by the biomaterials and medical device industry. Those terms and their definitions are utilized as positive selling points for very many medical devices. However, merely forty years ago, the term “bioactive” as applied to any material to be implanted in the human body was still something of a laboratory curiosity. It was the invention of one particular glass composition and the discovery over time of how that material behaved that created an entirely new approach with respect to how any material could and should interact with the human body. The invention, of course, by Larry L. Hench helped to revolutionize the field of implantable biomaterials and created the branch of materials known as bioactive materials. This is the brief story of Larry Hench and Bioglass ® .

Glass caused a revolution in health care when Bioglass was discovered by Larry Hench. It was the first material to bond with bone, rather than be encapsulated by fibrous tissue, launching the field of bioactive ceramics. Bioglass is also biodegradable. Almost 50 years on from its discovery that revolution continues. Bioactive glasses stimulate more bone regeneration than other bioactive ceramics, which is attributed to their dissolution products stimulating cells at the genetic level. This second discovery has changed the way clinicians, scientists, and regulatory bodies think about medical devices and the concept of bioactivity. The original 45S5 Bioglass has only recently found really widespread use in orthopedics, having regenerated the bones of more than 1.5 million patients. Its full potential is still yet to be fulfilled. This article takes the reader from Hench's Bioglass 45S5 to its clinical uses and products, before giving examples of nonsurgical products that now use Bioglass, from consumer products, such as toothpaste, to cosmetics. Other glasses have also found important health care applications, such as borate-based glasses that heal chronic wounds. The revolution looks set to continue as new health care applications are being found for bioactive glasses, contributing to extending the glass age.

Journal of Biomedical Materials Research Part AVolume 104, Issue 4 p. 819-820 Obituary In Memoriam Larry L. Hench, Ph.D. 1938 – 2015 Frederick J. Schoen M.D., Ph.D., Corresponding Author Frederick J. Schoen M.D., Ph.D. Executive Vice Chairman Department of Pathology, Brigham and Women's Hospital; Professor of Pathology and Health Sciences and Technology (HST), Harvard Medical School, 75 Francis St, Boston, MA 02115Correspondence to: fschoen@partners.org, dspinode@gmail.comSearch for more papers by this authorDavid C. Greenspan Ph.D., Corresponding Author David C. Greenspan Ph.D. President Spinode Consulting, 801 Brandywine Ct, St Augustine, FL 32086Correspondence to: fschoen@partners.org, dspinode@gmail.comSearch for more papers by this author Frederick J. Schoen M.D., Ph.D., Corresponding Author Frederick J. Schoen M.D., Ph.D. Executive Vice Chairman Department of Pathology, Brigham and Women's Hospital; Professor of Pathology and Health Sciences and Technology (HST), Harvard Medical School, 75 Francis St, Boston, MA 02115Correspondence to: fschoen@partners.org, dspinode@gmail.comSearch for more papers by this authorDavid C. Greenspan Ph.D., Corresponding Author David C. Greenspan Ph.D. President Spinode Consulting, 801 Brandywine Ct, St Augustine, FL 32086Correspondence to: fschoen@partners.org, dspinode@gmail.comSearch for more papers by this author First published: 23 January 2016 https://doi.org/10.1002/jbm.a.35665Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume104, Issue4April 2016Pages 819-820 RelatedInformation

The physical texture of implant surfaces are known to be one important factor in creating a stable bone-implant interface. Simple roughness parameters (for e.g., Sa or Sz) are not entirely adequate when characterizing surfaces possessing hierarchical structure (macro, micro, and nano scales). The aim of this study was to develop an analytical approach to quantify hierarchical surface structure of implant surfaces possessing nearly identical simple roughness. Titanium alloys with macro/micro texture (MM) and macro/micro/nano texture (MMN) were chosen as model surfaces to be evaluated. There was no statistical difference (p > 0.05) in either Sa (13.56 vs. 13.43 µm) or Sz (91.74 vs. 92.39 µm) for the MM and MMN surfaces, respectively. However, when advanced filtering algorithms were applied to these datasets, a statistical difference in roughness was found between MM (Sa = 0.54 µm) and MMN (Sa = 1.06 µm; p < 0.05). Additionally, a method was developed to specifically quantify the density of surface features appearing similar in geometry to natural osteoclastic pits. This analysis revealed a significantly greater numbers of these features (i.e., valleys) on the MMN surface as compared to the MM surface. Finally, atomic force microscopy showed a rougher nano-texture on the MMN surface compared with the MM surface (p < 0.05). The results support recent published studies that show a combination of appropriate micron and nano surface results in a more robust cellular response and increased osteoblast differentiation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1083-1090, 2016.

nerve regeneration. T main body of research involving bioactive glasses (BGs) has been devoted to applications in orthopedics and dentistry, given that the original composition 45S5 BioglassTM was developed to treat non-self-healing bone defects, such as bullet trauma or cancer. Because of their high bioactivity, BGs directly bond to bone. That bioactivity recently has been appreciated to extend to interaction with soft tissues as well. Many of the cellular processes involved in the early stages of soft tissue regeneration are affected by ionic dissolution products released by BGs, and an important aspect of BG applications in soft tissue repair strategies is their angiogenic potential. Fixation of shoulder prostheses (e.g., rotator cuff repair)

An Introduction to Bioceramics, pp. 455-462 (2013) No AccessBIOACTIVE GLASS FOR TOOTH REMINERALIZATION AND PAIN DESENTIZATIONDavid C. Greenspan and Larry L. HenchDavid C. Greenspan and Larry L. Henchhttps://doi.org/10.1142/9781908977168_0031Cited by:0 PreviousNext AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Library ShareShare onFacebookTwitterLinked InRedditEmail Abstract: The following sections are included: INTRODUCTION NOVAMIN® AND SENSITIVITY: MODE OF ACTION ROLE OF pH AND IONIC RELEASE EVIDENCE OF EFFICACY FOR CSPS COMMERCIALIZATION OF CSPS FOR TREATING TOOTH SENSITIVITY CONCLUSION REFERENCES FiguresReferencesRelatedDetails An Introduction to BioceramicsMetrics History PDF download

OBJECTIVE:The objective of this study was to determine the ability of a calcium sodium phosphosilicate (NovaMin) particulate to occlude dentin tubules, and to characterize the nature of the occlusion through a number of in vitro studies.METHODS:Four experiments were designed to demonstrate the ability of NovaMin to 1) rapidly occlude tubules, 2) remain on the dentin surface in the face of acid challenges, and 3) form a biologically stable hydroxycarbonate apatite layer on the surface of dentin. Bovine dentin samples, polished to 1200 grit silicon and etched in 40% w/w o-phosphoric acid solution for 15 minutes to remove the smear layer, were employed in all four experiments. Four different experimental techniques were used to evaluate the effects of NovaMin and other marketed calcium-based products on tubule occlusion in 1) a single-treatment model, 2) a 10-day acid challenge cycling model to evaluate tubule occlusion, 3) a 10-day acid challenge cycling model to evaluate changes in surface hardness, and 4) a calcium-release model. Samples were assessed for tubule occlusion by scanning electron microscopy, surface mineralization by microhardness, and calcium release by inductively coupled mass spectroscopy.RESULTS:For the single-treatment model, statistical analysis showed that all treatment groups had statistically fewer open tubules than the control group (untreated; p < 0.001), and that the NovaMin group occluded significantly more tubules than the Quell group (p < 0.001). For the cycling models, after a one-time brushing with the NovaMin (SootheRx) dentifrice, significantly fewer open tubules were visible compared to the untreated control (p < 0.001). After the 10-day cycle, there were few visible open tubules on the samples treated with SootheRx, a significant reduction when compared to the control samples (p < 0.001). The hardness of dentin treated with NovaMin during the 10-day cycle was significantly greater than sound and demineralized dentin (p < 0.001). The calcium-release model demonstrated NovaMin-based dentifrices released less calcium initially compared to the other treatment groups. After four hours, a higher release of calcium was observed that was sustained over 24 hours.CONCLUSION:NovaMin adheres to an exposed dentin surface and reacts with it to form a mineralized layer. The layer formed is resistant to acid challenges and is mechanically strong. The continuous release of calcium over time is suggested to maintain the protective effects on dentin, and provide continual occlusion of the dentin tubules.

The primary objective of this work was to develop a method of quantifying the levels and source of calcium and phosphate deposited on dental hard tissue from a novel calcium phosphosilicate (NovaMin) material using neutron activation analysis (NAA). A second objective was to explore the utility of radiotracing to determine dentin porosity following exposure to calcium phosphosilicate.Neutron activation was used to create isotopes of Ca and P in the calcium phosphosilicate particles. Gamma radiation emitted from these isotopes was used to identify and measure their uptake (concentration) onto dental hard tissue. Three experiments were conducted to explore calcium and phosphate uptake to dental hard tissue: 1) a dose response to quantify the relative levels of calcium and phosphate deposited on dental hard tissue as a function of calcium phosphosilicate dose; 2) the effect of calcium phosphosilicate particle size on the relative levels of calcium and phosphate uptake; and 3) the permeability of calcium phosphosilicate-treated dentin by employing the radiotracer technetium. For all experiments, extracted bovine incisors were employed as the test substrate.The results indicate there is a strong dose relationship between the wt% and particle size of calcium phosphosilicate in the dentifrice formulation and new Ca and P deposition. At above 5.0 wt% calcium phosphosilicate, there appears to be an exponential increase in the number of counts from the tooth surface. Finer particle size calcium phosphosilicate appears to deposit much higher levels of Ca and P than the larger range of particle sizes. The results from the technetium study show that when treated with the dentifrice slurry containing calcium phosphosilicate, dentin shows only a slight amount of technetium infiltration, indicating a lowering of dentin permeability.This exploratory study has demonstrated that NAA and the use of radio isotopes have utility in monitoring the uptake of Ca and P into both dentin and enamel tooth structure. The data generated from these studies have shown that there is a dose dependence and particle size effect for calcium phosphosilicate on the deposition of calcium and phosphate to dental hard tissue.

UNLABELLED To determine and compare the clinical performance of formulations containing 7.5% calcium sodium phosphosilicate (NovaMin), 5% potassium nitrate, and 0.4% stannous fluoride for the management of dentin hypersensitivity. METHODS This was a single-center, randomized, double-blind, parallel-group design with a duration of 12 weeks. The study included a total of 120 subjects and measured sensitivity to cold water and air blast by the use of a visual analogue scale. Measurements were taken at baseline, two, four, and 12 weeks. RESULTS All three products significantly reduced sensitivity versus baseline at each time point, although the calcium sodium phosphosilicate (NovaMin) dentifrice reduced sensitivity significantly more than the others at the two- and four-week time points. At the two-week time point, for air and water, respectively, the dentifrice containing NovaMin reduced sensitivity 45% and 49%, the stannous fluoride gel 30% and 26%, and the potassium nitrate dentifrice 35% and 34%. At the 12-week time point, the dentifrice containing NovaMin reduced sensitivity 87% and 91%, stannous fluoride gel 87% and 85%, and potassium nitrate dentifrice 84% and 79%. CONCLUSION In this study, all three products were effective. Compared to the potassium nitrate and stannous fluoride formulations, the dentifrice containing NovaMin provided more substantial and significant improvements at the early time points.

OBJECTIVE NovaMin is technically described as amorphous sodium calcium phosphosilicate, and has been shown in laboratory studies to rapidly occlude dentin tubules through the deposition of particles that react to form a protective layer, similar to bone mineral, on the dentin surface. NovaMin was originally developed as a bone regenerative material and is highly biocompatible. The objective of this pilot study was to compare the safety and effectiveness of two prototype formulations containing 2.5% and 7.5% w/w NovaMin to a placebo dentifrice for the treatment of dentin hypersensitivity. METHODS This was a randomized, double-blind, placebo-controlled pilot study. Sixty-six subjects with a confirmed diagnosis of dentin hypersensitivity were randomized to one of three treatments: 2.5% NovaMin, 7.5% NovaMin, or placebo. Two standard test stimuli, tactile and thermal air, were applied to sensitive cervical dentin surfaces. Subjects recorded the intensity of sensitivity in response to each stimulus on a visual analog scale at baseline, and after two, four, and eight weeks of twice-daily product use. Oral soft tissues were examined and spontaneous reports of adverse experiences were also monitored. RESULTS Comparison of the mean change from baseline among the three treatment groups indicated a meaningful reduction in sensitivity scores in the 7.5% group that was significant compared to reductions observed in the placebo control group at all time points. CONCLUSION The results of this study are supportive of the incorporation of NovaMin into products intended for the reduction of dentin hypersensitivity.

A class of melt quenched silicate glasses, containing calcium, phosphorus and alkali metals, and having the ability to promote bone regeneration and to fuse to living bone, is produced commercially as Bioglass, The changes in structure associated with reacting the bioglass with a body fluid simulant (a buffered Tris (hydroxymethyl)aminomethane growth medium solution or a blood plasma-like salt simulated body fluid) at 37 degrees C have been studied using both high energy and grazing incidence x-ray diffraction. This has corroborated the generic conclusions of earlier studies based oil, the use of calcia-silica sol-gel glasses whilst highlighting the important differences associated with glass composition; the results also reveal the more subtle effects oil reaction rates of the choice of body fluid simulant. The results also indicate the presence of tricalcium phosphate crystallites deposited onto the surface of the glass as a precursor to the growth of hydroxyapatite, and indicates that there is some preferred orientation to their growth.

PURPOSE:To evaluate the efficacy of a dentifrice containing calcium sodium phosphosilicate (NovaMin) study versus a placebo and a commercially-available SrCl2 containing dentifrice for the treatment of dentin hypersensitivity.METHODS:This was a 6-week, randomized, parallel-arm, double-blind clinical study. 71 subjects ranging in age from 21 to 56 years old completed the study. Evaporative and thermal stimuli were used to measure pain using a VAS scale. Measurements were obtained at baseline, 2 weeks and 6 weeks.RESULTS:The placebo and the NovaMin groups showed a statistically significant decrease in sensitivity by both measures after 6 weeks (P < 0.05). The SrCl2 group showed a statistically significant decrease from baseline at the 2-week time point, but not at the 6-week time point for the evaporative stimulus. The percent reduction in sensitivity at 6 weeks for the NovaMin test group was 35% for air and 39% for cold water stimulus, versus 11% for air and 22% for cold water for the SrCl2 paste. The reductions for the placebo paste were 21% for the air stimulus and 18% for water. A cross tabulation measure of the reduction in sensitivity at each time point for all three treatments showed that the NovaMin product was more effective than either of the other products. For the air stimulus in the NovaMin group, 58% of subjects improved at each time point compared with 26% for the SrCl2 group and 20% for the placebo group. These results demonstrate that the NovaMin dentifrice was more effective at reducing sensitivity compared with a commercial dentifrice and placebo control.

In this study, in order to observe the effect of Bioglass and its ionic products on human esteoblasts growth cycle in vitro, the ionic products of Bioglass have been introduced to a cell culture medium by dissolving Bioglass particles in Dulbecco's modified Eagle's medium (DMEM) at 37 degrees C for 24 h; this was used as the experimental medium, while DMEM without Bioglass modification was used as the control medium. Human osteoblasts isolated from trabecular bone were treated by the two media and the timing of the osteoblast growth cycle was examined. Cell growth curves were derived after 7 days. Also, human osteoblasts were treated for 1-6 days by the two media, and the G(1), S, G(2) phase percentages of osteoblasts were recorded by flow cytometry every day, resulting in the cell proliferation activity index: SPF (S-phase fraction) and PI (proliferation index). The difference in cell growth was shown after the second day of culture (p < 0.01), and cell growth in the experimental groups was greater than in control groups. The SPF and PI of the experimental groups were also higher than the control groups in 2 days of culture (p < 0.05 and p < 0.01), which indicates that the growth cycle of the human osteoblasts in experimental medium is about 2 days. In conclusion, Bioglass can promote osteoblast proliferation, reducing the human osteoblast growth cycle to pass through G(1) and S phase and then enter G(2) phase quickly.

AbstractA class of melt‐quenched silicate glasses, containing calcium, phosphorus and alkali metals, and having the ability to promote bone regeneration and to fuse to living bone, creating strong implants with less danger of interfacial instability than previous materials, is produced commercially as Bioglass® and sold under the brand names of PerioGlas®, NovaBone® and NovaBone‐C/M®. We have collected the first high energy X‐ray and neutron diffraction data, on this important material in the hope of providing more direct experimental insight into the glass structure. Similarly, the first solid state MAS (magic angle spinning) 29Si, 31P, and 23Na NMR data on the material is presented. The diffraction data has been modeled using the reverse Monte Carlo (RMC) method to allow the identification of the atomic‐scale structural features present; the solid state NMR data is used explicitly within the model‐building process as a constraint on the connectivity of the network. The 29Si NMR suggests that the host silica network primarily consists of chains and rings of Q2 SiO4 tetrahedra, with some degree of cross linking as represented by the presence of Q3 units. The diffraction‐based RMC model suggests a Na–O distance of 2.35 Å and a corresponding coordination of ∼ 6; the coordination number is supported by the 23Na NMR data presented here which reveals that the likely sodium environment is six‐coordinate in pseudo‐octahedral arrangement. The RMC model provides evidence for the non‐uniform distribution of Ca, which is in line with previous molecular dynamics simulation results, and the data is also suggestive of CaO as the associated structural motif within the high calcium content regions of the glass.