Bioactive glass compositions and methods of treatment using bioctive glass

This application is a continuation-in-part application of copending U.S'. Application Serial No. 08/597,936 filed February 7, 1996, the disclosure of which is hereby incorporated by reference. This application is further a continuation-in-part application of copending U.S.

Provisional Application Serial No. 60/010,795 filed January 29, 1996, the disclosure of which is hereby incorporated by reference.

FIELD OF THE INVENTION

The présent invention relates to bioacüve glass compositions. More particularly, the présent invention relates to improved compositions of bioactive glass induding particles having combinations of size ranges significantly lower than previous compositions. The présent invention also relates to various methods of treatment induding the use of sudi bioactive giass compositions.

BACKGROUND OF THF. INVENTION

Human tooth enamel naturally undergoes a process of demineralization. Exposure of enamel te saliva and food slowlv leaches minerais from teeth and eventuallv leads to increased susceptibility to decay. This process of demineralization results in incipient caries which are typical’y very small defects in the enamel surface that are thus far usually left untreatem. Carions dentin demineralization also may occur in patients that hâve exposed régions o: dentin resulting from decay below the ccmentum-enamd junction. Accordindv. there has reen much work associated with slowing this naturel process of demineralization induding ne application of fiuoride and other topical treatments.

Fc-enampie, U.S. Paient No. 5,427,768 discloses calcium phosphate solutions which are supersatumted with respect to calcium phosphate solids and carbon dioxidc. The solutions depesit calcium phosphate compounds with or without fluoride on and in the tooth weakn-e-ssez such as dental caries, exposed root, or dentin. U.S. Patent Nos. 5,26S. 167 and

3C 5.03“.é3^c disclose the use of amorphous caicium compounds such as amorphous calcium phosphate. amorphous calcium phosphate fiuoride and amorphous calcium carbonate ü 1Ü818 phosphate for use in remineralizing teeth. These amorphous compounds, when applied to dental tissue prevent and/or repair dental weaknesses. The disadvantages of these methods include (1) a low pH necessary for the application which can be an irritant, (2) rapid reaction results in a very short term effect, (3) since these methods use solutions, the actual réactions 5 are diffioult to control from patient tp patient, and (4) since the reactions are rapid and of short duration, the procedure must be repeated to maintain the effect. Also, both methods require maintaining at least one solution with pressurized CO, prior to mixing delivery which makes the method difficult to incorporate into an over-the-counter procedure.

Demineralization eventually leads to cavitation of enamel coating such that there is exposure of the underlying tooth structure. Typically, this type of decay is treated bv drilling out the cecayed région and inserting a semi-permanent filling material. However, there is a need for a less invasive means ofarresting and reversing decay.

Frophylactic pit and fissure sealants hâve become widely used in preventing decav in arecs thm are particularly at risk for decay. These sealants hâve includcd polymer or other 1<5 cenner.*3 that require a dry application and the use of a fixing agent These sealants are tempera' and do not provide for an optimal seal.

Lcners and bases are materials that are used to treat ncwly exposed tooth surfaces such as Chose surfaces exposed by drilling. After a cavitv is prepared, it is common practice to appiy a imer or base before filling the cavitv with a filling material. Λ lincr is a thin coating 20 of ma’.end and a base is a thicker coating. Liner and base materials are designed to decrease permeabLity of dentin at the tooth material interface and protevt against microlcakagc around and throuph the fill material and to seal dentin tubules. Earlier liners or cavitv vamishes incrude materials such as organic gums dissolved in organic solvents. Upon évaporation of the crganic solvent, the gum is left behind. Disadvantages associated with these organic 25 gums are well documented and include leaky junctions, lack of adhérence, acid vulncrabiIity, etc. Amdr.er method of lining is disclosed in U.S. Patent No. 4.538,^l>90 which describes apphmg a. 1 to 30% w/v neutral oxalate sait solution, such as dipotassium oxalate to the smem iayer and then applying a 0.5 to 3% w/v of an acidic oxalate sait solution such as moneprtassium monohvdrogen oxalate to the layer. Research has shown poor seal occlusion 30 of the tubmes with this method.

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U.S. Patent No. 5,296,026 discloses glass phosphate cernent compositions and methods for their use as surgical implant materials to fill cavities in bone and canals in teeth. The cernent compositions include P₂O₅, CaO, SrO and Na₂O in combination with an aqueous liquid with or without therapeutic agents. Mixing the powder and liquid results in a hardenirg reactions. When the cernent is implanted into hard tissuc, it serves as a filler/graft material and along with the release of leachable constituents it can assist in the healing and maintenance of healthy bone.

Various bioactive and biocompatible glasses hâve been developed as bone replacement materials. Studies hâve shown that these glasses will induce or aid osteogenesis 10 in a physiologie Systems. Hench et al, J. Biomed. Mater. R es. 5:117-141 (1971). The bond developed between the bone and the glass has been demonstrated to be extremely strong and stable Piotrowski et al., J. Biomed. Mater. Res. 9:47-61 (1975). Toxicology évaluation of the glasses has shown no toxic effects in bone or soft tissuc in numerous in vitro and'in vivo models. Wilson et al., J. Biomed. Mater. Res. 805-817 (1981). The glass has been reported 15 to be bacneriostatic or bacteriocidal most likely related to the change in pH induced by the dissolution of the ions from the surface of the glass and lack of bacterial adhérence to the glas s surface. Stoor et al, Bioceramics Vol. 8 p. 253-258 Wilson et al (1995).

Tne bonding of the glass to bone begins with the exposurc of the glass to aqueous solutions. Na' in the glass exchanges with H- from the body fluids causing the pH to încrease. Ca and P migrate from the glass forming a Ca-P rich surface laver. Underlying this Ca-? rich is a laver which becomes increasingly silica rich due to the loss of Na. Ca and P ions (U.S. Patent No. 4,851,046).

The behavior of the bioactive glass as solid implants in a dental application was reperted by StanJey et al., Journal of Prostetic Dentistry. Vol. 58. pp. 607-613 (1987).

Repiicate :ooth forms were fabricated and implanted into extracted incisor sockets of adult baboons. Successful attachment of the implants to sumounding bone was seen after histologie exazninaticn at six months. Clinical application of this technique is presently available for humanusa. Endosseous Ridge Maintenance Implant EFUMl'C. Particulate bioactive glass has been. used for periodontal osseous defect repair (US Patent No. 4.851,046) utilizing a size rance of9C-7lO pm and a compositional range described in the following chart.

Component Weight Pc cmtage

<td> SiO₂</td><td> 40-55</td>

<td> CaO</td><td> 10-30</td>

<td> Na₂0</td><td> 10-35</td>

<td> P₂0₅</td><td> 2-8</td>

<td> CaF₂</td><td> 0-25</td>

<td> B₂0₃</td><td> 0-10</td>

Previously described data has shown that 60% silica is beyond the limit of bioactivc melt derived glasses. Okasuki et al. Nippon Seramikbusu Kyokai Gakijutsu Konbuski, Vol. 99, pp. 1-6(1991).

The 9G-710 pm size range was determined to be the most effective for pcriodontal applications when in direct contact with bone. However. size ranges smaller than 90 pm were ineffective due to their high rate of reactivity and rapid résorption at the bony sue. Mcreover, size ranges smaller than 90 pm were determined to be ineffective in soft tissue . sites also due to the presumption that the smaller particles were removed by macrophages (see U.S. Patent No. 4,851,046). A size range of less than 200 pm was also found to be ineffective in certain bone defects (see U.S. Patent No. 5,204,106) due to the high rate of reactivity.

U.S. Patent No. 4,239,113 (the '113 patent) also describes the use of a bone cernent. The '113 patent only discloses bioactive glass ceramic powder having a particle size of 102ΟΞ microns. Moreover, the '113 patent also requires the use of niethylmethacrylate (cc)polymers and vitreous minerai fibers.

None of the foregoing methods or compositions provide for the combined advantaees of both easy application and adhérence to tooth structure including pénétration into ver}¹srr.all tcoth structure defects and the opportunity for continued chemical and physical interaction wifn tooth structure after application.

According’.y, it is an object of the présent invention to provide a composition capable of cheminai and physical interaction with tooth structure that is easily applied and reaciilv adhèrent to tcoth structure.

It is a further object of the invention to provide a method of usine such a bioactive ’

glass composition to treat a variety of dental and other conditions.

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SUMMARY OF THE INVENTION

The présent invention relates to, for example, a bioactive glass composition including particulate bioactive and biocompatible glass including by weight percentage:

SiO₂40-60

CaO10-30

Na₂010-35

P₂0₅2-8

CaF₂0-25

B₂0₃0-10

K₂O0-8

MgO0-5.

the particulate bioactive and biocompatible glass including particles iess than 90 pm and an effective remineraiizing amount of particles less than about 10 pm. The présent invention also relates to various methods of dental treatment including remineralization, sealing fissures and/cr pits. lining tooth structure, treating decay, capping pulp. treating sensitive post surgical tooth structure, sealing dentinal tubules. and surface for tissue régénération.

BRIEF DESCRIPTION OF THF DRAWINGS

Figure 1 is a dentin control surface that has been treated with 37% phosphoric acid for seconds to remove any smear layer after sectioning and grinding te emulate clinical sensitivity. The surface has not been treated with bioactive glass in accordance with the 25 présent invention (2000X magnification).

Figure 2 is a dentin control surface that has been treated with 37% Phosphoric acid for seconds t.o remove any smear layer after sectioning and grinding to emulate clinical sensitivity. The surface has not been treated with bioactive glass in accordance with the présent invention (3000X magnification).

Figure 3 is a dentin surface that has been treated with an acid ctch and treated with a bioactive glass composition in accordance with the présent invention, in water and ulÿcerin for 2 minutes (Particle size range submicron to 90 pm, 1000X mag ni fi cation).

Figure 4 is a dentin surface that has been acid etched and subsequently treated with a 5 bioactive glass composition in accordance with the présent invention in water and elvcerin for 2 minutes. The surfaces were subsequently agitated and water rinsed for 2 minutes (Particle size range submicron to 20 pm, 2000X magnification).

Figure 5 is a dentin surface that has been aeïd etched and subsequently treated with a bioactive glass composition in accordance with the présent invention and placed in water for 10 3 cays. There was no subséquent agitation, but the surface was water rinsed for 2 minutes (Particle size range submicron to 90 pm, 2000X magnification).

Figure 6 is a dentin surface that has been acid etched and subsequently treated with a bioactive glass composition in accordance with the présent invention in water and toôthpn.sie for 2 minutes with agitation and a subséquent 2 minute water rinse (Particle size range submicron to 3 pm, 3000X magnification).

Figure ~ is a dentin surface that has been acid etched and treated with a bioactivc glass composition in accordance with the présent invention in water and toolhpaste for 2 minutes with agitation and water rinse for 2 minutes (Particle size range submicron to 3 pm. 3500X magnification).

2'.? Figures ? and 9 each include a dentin surface which has been acid etched v.itli phosphore acid, treated with a bioactive glass in accordance with the présent invention for 2 minutes an.d immersed in a phosphate buffered saline for 5 days (Taiticlc size rance submicron).

Figure K depicts a dentin surface that has been acid etched and subsequenth treated 25 with a single application of a bioactivc glass composition in accordance with the présent invention.

Firure 11 depicts a dentin surface that has been acid etched and treated with titrée sepamtc applications of a bioactive glass composition in accordance with the présent, invention.

Fig-jre 12 is a Fourier Transform Spectroscopy (FTIR) performed on samnles treated with cptimu.1 sizes and shaped particulate bioactive glass.

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DETAILED DESCRIPTION OF THE INVENTION

The présent invention provides a bioactive glass composition which is useful in, for example, enamel remineralization, incipient caries remineralization, carious dentin remineralization, caries prévention, arresting decay, reversing decay, anti-caries, pit and fissure sealants, prophylactic pastes, fluoride treatments, dentinal sealants, etc. It can also be included in toothpastes, liners, bases, gels, and restorative material e.g. packing, indirect pulp capping agent, etc. Compositions in accordance with the présent invention are also useful in the treatment of surfaces after periodontal surgery to decrease dentinal sensitivitv and enhar.ee tissue attachment. The compositions are active in treating various defects associated with a variety of dental and other conditions and actuallv chemically and physically bond to the tooth thereby remineralizing tooth structure.

As referred to herein. remineralization is the formation of hydroxyapatitc. The formation of hvdroxvapatite begins with exposure of a bioactive glass composition to aquecus solutions. It is believed that the sodium ions (Na-⁴-) in the bioactive glass exchanees with H- ions in body fiuids causing pH to increase. Calcium and phosphorus then migrate from the bicactive glass forming a calcium-phosphorous rich surface layer. An underlvina silica rich zene slowly increases as the sodium ion in the bioactive glass continues to exchar.ge with the hydrogen ion of the solution. After time. the calcium-phosphorous rich ’.ayer crystahizes into a hvdroxvapatite material. Collagen can become structurallv inteerated with the apatite agglomérâtes. As hereinafter referred to. an effective remineralizing amount is any amour.! capable of forming hvdroxvapatite.

As the term a tooth structure is used herein, it is intendcd to refer to any feature or features cf a tooth including but not limited to enamel. dentin. pulp. tooth root structure, cememum. root dentin. coronal dentin, any dental manufacture, etc.

A bicactive glass in accordance with the présent invention is a glass composition that wi'.i form a layer of hvdroxycarbonate apatite in vitro when piaced in a simulatcd bodv fluid. For example. the following composition by weight will provide a bioactive glassSiO₂

CaO

Na₂O

P₂0₅

CaF₂

B₂0₃

K₂O

MgO

40-60

10-30

10-35

2-8

0-25

0-10

0-8

0-5

Bioactive glasses with these properties provide a more efficacious material for interaction with the tooth structure. A biocompatible glass in accordance with the présent invention is one thsx does not trigger an overwhelmingly adverse immune response.

In accordance with the présent invention, it has been found that bioactive glasses of specified partiels sizes are particularly useful in trcating the abovc-mentioned conditions. Specifically, surprisir.g results are obtained by the présent invention where small and ver,· ' small particles are combined. For example, when compositions including small particles that are capable o: bonding with tooth structure (e.g. less than about 90 microns) as well smaller particles (e.g.. less than about 10) are used in combination, the larger of these particles adhéré to tooth structure and act as ionic réservoirs while the smaller are capable of entérine and lodginp inside of varions tooth structure surface irregularities. The larger of these particles provide a réservoir of additiona! calcium and phosphorous so that the mineralization. or depcsit_ng of me calcium phosphate layer begun by the small particles can continue. Additicrtai calcium and phosphorous can be leached to ail tooth structure as well as to particles which hâve become attached to the inside or at the openings of surface irrcuularities of tooth structure such as déminai tubuies. This in tum provides for continuation ofthe entire réaction, ar.d cantir.ued growth of the smaller of these particles which hâve lodued inside or over me openings of such surface irregularities and can resuit in effectively coatinu or fi 1 line the surface irregularity. This excess concentration of ions of calcium and phosphorous is necessam·· mr continuée reaction of the smaller of these particles to take place because the smaller par.ihes cuickly exhaust their ions as a resuit of their relatively hiuh surface area.

The larper cf these particles will react and releasc their ions more slowly as a ionuer term effect. Furthermore. the larger of these particles will mechanically abrade the k. ,.th surface opening various surface irregularities allowing small particles to enter and react with the surface irregularity.

This effect is very bénéficiai in a variety of applications. For example, in preventing caries or decay, the composition of the présent invention is capable of penetrating into the 5 depths of the smallest of surface irregularities and receiving a continued supply of ions from langer nearby particles so that it is able to grow after exhausting its stored ion supply. This is also ver/ usefiil in sealing pits and fissures and a much more effective and long lasting seal is octainedIc some embodiments of the présent invention, extremely small particles are used.

Fer example, particles that are in the range of 2 pm to submicron fit inside dèntin tubules that are approximately 1-2 pm in diameter. The occlusion of these tubules leads to a significant réduction in the amount of sensitivity after, for example, periodontal surgery. Preferably. a mixture cf particles less than two microns and larger than 45 microns in diameter are'used. It has been found that this combination vields a particularly effective composition.

Compositions in accordance with the présent invention generally do not requirc time to set. Previous compositions were easily washed away by mechanical abrasion caused by brushing, exposure to mild acids in food, salivary flow or other liquids which normally corne in contact with the teeth. However, some compositions in accordance with the présent invention hâve been able to generally withstand significant agitation, rinsing with water and long term soaking in simulated saliva for five days. Moreover. many of the small particles of the présent invention do not requirc a set time because they begin to chemically react and adhéré to tooth structure as soon as they corne into contact with thèse surfaces and fluids naturallv présent in the mouth. Although compositions in accordance with the présent invention nre effective with a single application, it is likely that multiple applications will be more efficucious.

Surprisingly, the relatively small bioactive particuiate glass of the présent invention does not generate a significant immune response. Morcover, it is generally not engulfed by macrophages and rendered inactive in this application.

The composition of the présent invention is capable of providing a bioactive laver that will form a new structural laver which is a lasting remineralization of tooth structure. This has beer. verifted by the reformation of a hydroxvcarbonate apatite laver on dentin surfaces ’* Y * λ after treatment with compositions in accordance with the present invention with Fourier Transform Infrared spectroscopy (FTIR).

In one embodiment in accordance with the present invention, the particles hâve a particle size of about 20 microns with about 30 percent of the particles less than 10 microns.

In another embodiment in accordance with the present invention the particles hâve an average particle size of 10 microns with at least-25% smaller than 2 microns.

The compositions of the present invention may be formulated into toothpaste. In fact, the particles may replace the silica currently used in toothpastes. The addition of fluoride in the glass composition will enhance and strengthen the tooth structure. In addition to direct 10 application of the bioactive glass to the teeth, the bioactive glass composition of the présent invention can also be applied in a saline or distilled water based medium.

The compositions of the present invention may also bc formulated into mouthwash. gel or they may be applied by a dentist as a paste.

Examples

The following working examples are non-limiting:

In vitro experiments were performed using a standardized slab of human tooth dentin from extracted teeth. These dises were eut from the extracted teeth using an Isomet diamond saw (Buchler Ltd.). The dises were 1.0 mm thick and the size of the tooth. The occlusal surfaces were ground on a sériés of wet silicon-carbide papers ranging from 320 to 600 grit. This ’-ves dene to standardize the test surfaces. The surfaces were treated with 37% phosphcric acid for 60 seconds to remove the smear layer crcatcd during the grindinu process and cper. and eniarge ail the dentin tubules (See Figures 1 and 2). The surface was rin.sed with distille-d water for 20 seconds and dried with a stream of oil free air. Each slab was spiit in hait and the experimental material placed on one-half of the spécimen as described m the examples. An untreated slab with open and enlarged tubules is shown in Figures 1 and 2

Scacming électron microscopv was performed on the slab surface in each sroup. The slabs were mour.ted on scanning électron microscope stubs using sliver paste. Ail specimens were vacuum dried, sputter coated and examined in a JEOL-T200 scanning électron microscope.

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EXAMPLE I

The starting product was a mixture containing (% by weight)

<td> SiO₂</td><td> 45</td>

<td> 5 CaO</td><td> 24.5</td>

<td> Na₂O</td><td> 24.5</td>

<td> P₂O_S</td><td> 6</td>

The mixture was melted in a covered platinum crucible at 1350° C for 2 hours to achieve hcmogenization. The mixture was later quenched in deionized water at 0°C. Fritted glass 10 was placed in an appropriate milling apparatus including bail mill, impact mill. The glass is milled for 2 hours and separated into appropriate size ranges.

The particle size range less than 90 pm was obtained using this process and confirmed by scanrting électron microscopy and laser light scattering technique (Coulter LS 100*). These mixtures were placed on the dentin slabs previously described.

The exposure times to the dentin varied between two minutes with scrubbing to 3 days with no agitation. The occlusion of the tubules is depicted in Figures 3-7. Visible in Figures 3-7 are total and partial occlusion of the dentin tubules with multiple size of small (1 5 pm) particles présent. In addition, larger particles that are visible that will act as réservoirs for the cr.emical composition. Early formation of hydroxyapatite crystals is beginninc on the 20 der.'.ir. surface confirmed b)· FTIR.

EXAMPLE 2

Figures 8 and 9 indicate the results obtainable by using submicron particles made in accordance w'ith Example 1. The samples of figures 8 and 9 are dentin surfaces which hâve beer. acid etched with phosphoric acid, treated with a bioactivc glass for 2 minutes and imrr.ersed in a phosphate buffered saline for 5 days. With the kick of large particles for réservoir activity, there was less complété régénération as confirmed bv FTIR.

EXAMPLE 3

Example 3 was conducted to illustrate the benefits associated with multiple applications of compositions in accordance with the présent invention. First, an acid etched 5 dentin surface was treated with a single treatment of bioactive particulate glass for two minutes and is depicted in Figure 10. A dentin surface which has been acid etched and treated three times for two minutes is depicted in Figure 11.

Figure 10 shows significant pénétration and occlusion of the tubules with a bonding over the surface of the dentin. There are not many large particles visible in Figure 10. In 10 Figure 11, there is even more significant pénétration and occlusion of the tubüles and a greater number of particles présent. This demonstrates the benefits associated with multiple application including the tubules as well as increased presence of larger réservoirs of Ca and P ions. This also demonstrates interparticle welding of the larger particles to the smaHer particles already bound to the surface.

.15

EXAMPLE 4

Example 4 further illustrâtes the benefits associated with the use of particles less than microns in combination particles greater than 45 microns in size. FTIR spectra for the fcllowirtg samples are included in figure 12 to illustrate remineralization:

<td></td><td> Sample No. 1</td><td> Control (untreated dentin surface)</td>

<td></td><td> Sample No. 2</td><td> Acid etched dentin surface</td>

<td> 25</td><td> Sample No. 3</td><td> Treated with particles of bioactive glass less than 2 microns in particle size for two minutes</td>

<td> 30</td><td> Sample No. 4</td><td> Treated with particles of bioactive glass wherein 40% were less than 2 microns. 15% were in the range of 8 to 2 microns, 15% were in the range of 8 to 20 microns. 15% were in the range of 20 to 38 microns and 15% were in the range of 38-90 microns.</td>

A-S illustrated in Figure 12, the control sample provides a représentative view ofthe spectrure of hvdroxycarbonate apatite (HCA). The shape of the peaks between wave number

U10818

1150 to 500 are very characteristic of HCA. In sample 2, the peaks are disrupted after treatment with the acid etchant, especially in the 1150 to 900 range. This indicates a loss of the minerai components of the tooth structure, Calcium and Phosphorous. Sample 3 shows a partial remineralization of the Ca and P on the tooth structure. Sample 4 was treated with the optimal size and shape mixture of bioactive glass and shows an almost complété remineralization. A photomicrograph of Sample 4 is included as Figure 11.

EXAMPLE 5

Comparative Example 5 shows the benefits associated with the use of particles less than 10 microns in combination with particles greater than 45 microns in size over the use of just particles less than 2 microns or 53-90μ. A control sample of untreated dentin surface was used ir. addition to treated surfaces as described below:

<td> Number of Applications</td><td> Sample Composition</td><td> Score</td><td> Observations</td>

<td> Single</td><td> 53-90/z</td><td> 2</td><td> About 50% occluded tubules with large particles présent</td>

<td></td><td> Control</td><td> 0</td><td> No particles présent</td>

<td> Single</td><td> &lt;2μ</td><td> a</td><td> Above ?0% closure. no large particles seen</td>

<td></td><td> Control</td><td> 0</td><td> Open tubules</td>

<td> Single</td><td> 50% 53-90μ 50% &lt;2/z</td><td> +3</td><td> 75%-ί- tubules occluded</td>

<td></td><td> Control</td><td> 0</td><td> Open tubules</td>

<td> Multiple</td><td> 53-90/2</td><td> 2</td><td> Partial closure of tubules with large particles présent</td>

<td></td><td> Control</td><td> 0</td><td> Minimal occlusion seen</td>

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<td> Multiple</td><td> &lt;2μ</td><td> 2</td><td> Partial closure of tubules with small particles présent</td>

<td></td><td> Control</td><td> 0</td><td> Minimal occlusion seen</td>

<td> Multiple</td><td> 50% 53-90μ 50% &lt;2μ</td><td> +3</td><td> Best results--tubules closed; difficult to find open tubules</td>

<td></td><td> Control</td><td> 0</td><td> Minimal occlusion seen</td>

Ali samples in the above Table were subjected to a moist environment for 24 hours and then dried for 48 hours.

As seen above, the combination of particles less than 2 microns and 53-90μ provided the best résulta. It is believed that the presence of both size ranges permits the smaller particles which hâve lodged in the tubules to continue growth after they hâve exhausted their own Ca and P ions and are abie to make use of such ions from other nearby larger particles acting as réservoirs of Ca and P ions.

«

OTHER EXAMPLES

The composition of the starting product for the following examples was the same as Example 1 except the level of SiO₃ was 45%, 55%, and 60%. Also. the method of préparation was different. The mixture was melted in a covered platinum crucible at 1350%; for 2 heurs to achieve homogenization. The mixture was poured into a slab, allowed to cool to room température and crushed with a hammer. Crushed glass fractions were then separatec by sieving through a standard screen. Fractions were then separated and retained.

Tue paraicle size range less than 90 pm was obtained using this process and confirmed by scanmrtg électron microscopy and laser light scattering technique (Coulter LS 100). These 2q mixtures were placed on the dentin slabs previouslv described.

Simples containing 45%. 55%. and 60% SiO_: were utilized in the préparations with the same résulta seen in Example 1. Again, the key to this data was the presence of the size range of particles. Présent in these examples are ranges up to 60% silica with a size range in particles from. submicron to 90 micron showing like reactions to Example 1 un me aentin surfaces.

Although the présent invention has been described in one or more embodiments, this description is not intended to in any way limit the scope of the daims.