WO2015092815A1 - Bioconversion de verres de fluorophosphate contenant du magnésium et procédé de fabrication associé - Google Patents

Bioconversion de verres de fluorophosphate contenant du magnésium et procédé de fabrication associé Download PDF

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Publication number
WO2015092815A1
WO2015092815A1 PCT/IN2014/000760 IN2014000760W WO2015092815A1 WO 2015092815 A1 WO2015092815 A1 WO 2015092815A1 IN 2014000760 W IN2014000760 W IN 2014000760W WO 2015092815 A1 WO2015092815 A1 WO 2015092815A1
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calcium
glass
magnesium
composition
fluoride
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PCT/IN2014/000760
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English (en)
Inventor
Rajkumar GURUSAMY
Pugalanthipandian SANKARALINGAM
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Pandian Bio-Medical Research Centre
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    • CCHEMISTRY; METALLURGY
    • C03GLASS; MINERAL OR SLAG WOOL
    • C03CCHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C3/00Glass compositions
    • C03C3/12Silica-free oxide glass compositions
    • C03C3/23Silica-free oxide glass compositions containing halogen and at least one oxide, e.g. oxide of boron
    • C03C3/247Silica-free oxide glass compositions containing halogen and at least one oxide, e.g. oxide of boron containing fluorine and phosphorus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/10Ceramics or glasses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/12Phosphorus-containing materials, e.g. apatite
    • CCHEMISTRY; METALLURGY
    • C03GLASS; MINERAL OR SLAG WOOL
    • C03CCHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C4/00Compositions for glass with special properties
    • C03C4/0007Compositions for glass with special properties for biologically-compatible glass
    • C03C4/0014Biodegradable glass
    • CCHEMISTRY; METALLURGY
    • C03GLASS; MINERAL OR SLAG WOOL
    • C03CCHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C4/00Compositions for glass with special properties
    • C03C4/0035Compositions for glass with special properties for soluble glass for controlled release of a compound incorporated in said glass
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/02Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention describes the composition of magnesium oxide added fluorophosphate glasses by melt quenching technique for different bio-medical applications.
  • autologous bone remains the preferred material in bone graft and regenerative procedures.
  • This bone taken from a secondary site within the body is often excised and reimplanted. It contains both the inorganic mineral hydroxyapatite as well as the cell characteristics of bone. Even this is not a living material, but can remodel into new and functional bone.
  • Autografts may be combined with supplementary agents such as growth factors or synthetic bone replacement materials.
  • the disadvantage of autologous bone usage is the creation of a secondary trauma site that has to heal. Further, its usage is limited by availability.
  • the materials taken from cadavers (allograft) are not constrained by supply. The above material is often demineralized, leaving behind a collagenous scaffold for the growth of a new bone. Further, it fails to function as an osteoinductive but only as osteoconductive material. These materials always carry the risk of disease transmission with them.
  • bioactive glass The third generation of materials used for the regenerating new bone is bioactive glass. These materials have the unique ability to form a chemical bond with the host tissue when implanted. Thus, it allows to retain the structural integrity and to resist movement at the impjantation site. The chemical bond that occurs through the formation of hydroxyapatite on the glass surface converts the glass into bone rich material. The beneficial effects of bioactive glasses on cellular growth also substantiate to their use.
  • the bioconversion rate of phosphate based glasses called bio active glasses have been improved by the addition of a low, non toxic concentration of fluoride salts (CaF 2 ) and are called fluoro-phosphate glasses.
  • fluorine added phosphate glasses called as "fluorophosphate glasses” have better bio conversion rate the glass have limited use due to their high dissolution rate which gives rise to large pH changes. Attempts have been made to control the pH changes by the addition of high valency ions.
  • the present invention discloses the addition of MgO in the glass network. Magnesium oxide acting as a network modifier results in altered glass network, structure and hence the physico-chemical properties of the glass sample.
  • Pure vitreous phosphorus pentoxide (P 2 0 s ) is chemically unstable on account of hydrolysis of the P— O— P bond by atmospheric moisture.
  • MgO is of interest from a physiological viewpoint because Mg 2+ is one of the few rare elements known to play a physiological role in positively influencing bone formation and its strength. It is to be noted that by the addition of MgO in glasses, the Mg 2+ ion forms a component of the new bone that is formed.
  • the present invention discloses the different composition of magnesium oxide added fluorophosphate glasses P 2 0 5 — CaO— a 2 0— CaF 2 — MgO (hereafter termed, respectively, as MgFPl, MgFP2, MgFP3, MgFP4 and MgFP5) are prepared by keeping the ratio of P/Ca as a constant.
  • MgFPl, MgFP2, MgFP3, MgFP4 and MgFP5 are prepared by keeping the ratio of P/Ca as a constant.
  • MgFPl, MgFP2, MgFP3, MgFP4 and MgFP5 are prepared by keeping the ratio of P/Ca as a constant.
  • MgFPl, MgFP2, MgFP3, MgFP4 and MgFP5 are prepared by keeping the ratio of P/Ca as a constant.
  • MgFPl, MgFP2, MgFP3, MgFP4 and MgFP5 are prepared by keeping the ratio of P/Ca as a constant.
  • the present invention discloses the composition with different contents of P 2 0 5 -CaO-Na 2 0-CaF 2 -MgO (MgFPl, MgFP2, MgFP3, MgFP4 and MgFP5) glass systems are prepared using normal melt-quench method by keeping the ratio of P/Ca is constant.
  • the physico-chemical and bioactivity of the magnesia added fluorophosphate were assessed using density measurements, ultrasonic velocity measurements, x-ray diffraction (XRD) patterns, Fourier transform infrared spectra (FTIR), pH variation of the sample glasses soaked 21 days in the laboratory prepared simulated body fluid (SBF) solution, scanning electron microscope (SEM) images, energy dispersive x-ray spectra (EDS) and x-ray photo electron spectrograph (XPS).
  • Toxic nature of the selected glass sample was assessed using cytotoxicity study in cell culture lines. Bioconversion was also accessed by in vivo studies of implantation of the glass into animal bone followed by confocal laser scanning micrograph (CLSM) images. The results obtained before, after in vitro and in vivo studies are discussed in terms of change in structure, stability, mechanical properties, bone-bonding ability and bio conversion of the prepared glass samples.
  • MgO added fluorophosphate glass composition P 2 0 5 — CaO— Na 2 0— CaF 2 — MgO, methods of preparation and use thereof are disclosed.
  • the glasses can be used for different biomedical applications such as prosthetic implants, stents, screws, plates, tubes, controlled drug delivery etc.
  • the addition of fluorine and magnesium is made at the expense of Na 2 0 content in the glass composition and keeping the P/Ca ratio as constant.
  • the glasses were prepared in the mentioned compositions include various salts in mol% with the following ranges:
  • P 2 0 5 Ammonium di hydrogen phosphate, Phosphorous chloride, ammonium phosphate, calcium phosphate, sodium phosphate, silver phosphate etc.
  • the cell viability test showed no cytotoxicity on ⁇ assays and hence these glasses are suitable for synthetic bone graft material for human use.
  • the in vivo studies were done on rabbit by implanting the optimised sample MgFP5 into the femoral condyle. SEM and CLSM studies on the un- decalcified sectioning of the implant after 10 weeks confirm the bioconversion of glass into bone.
  • Magnesia added fluorophosphate glasses were prepared by melting the homogeneous mixture of phosphate, calcium, sodium, magnesium and fluoride salts followed by sudden quenching of the melt.
  • the derivatives of phosphate, calcium, sodium, magnesium and fluoride salts were weighed accurately and ground using mortar and pestle/ planetary ball mill.
  • the mixture was fed into alumina crucible and then preheated at a temperature ranging from 140 °C to 190 °C for 1 h in a closed furnace and cooled to room temperature at a rate of 1 °C per minute.
  • the preheated mixture was ground using mortar and pestle/ planetary ball mill.
  • the mixture was taken in a platinum crucible and melted at the temperature ranging from 1050 °C to 1400 °C for 1 h. The temperature in the furnace was kept constant throughout the process. The melt was poured in a preheated graphite/ steel mould and cooled to room temperature. In this method, the entire synthesis protocol is successfully done without the usage of any toxic chemicals.
  • the method for preparing magnesium added fluorophosphate glasses compare the following steps:
  • the obtained solid glass sample is annealed at 300 °C - 500 °C for 1 h and cooled at the rate of 0.5 °C - 2 °C per minute.
  • the powdered mixture was melted in a platinum doped with 10% Rhodium crucible and heated at the temperature of 1050 °C - 1400 °C for 1-4 h and then quenched in a preheated stainless steel/ graphite mould at a temperature of 300 °C - 600 °C and then cooled.
  • the prepared glass sample was annealed at 300 °C- 500 °C for 1 h then cooled at the rate of 0.5 °C - 2 °C per minute to release the stress in the glass sample.
  • the prepared glass sample was cut into required size and shape using diamond cutter.
  • the code for the present sample is called as MgFPl.
  • the powdered mixture was melted in a platinum doped with 10% Rhodium crucible and heated at the temperature of 1050 °C - 1400 °C for 1-4 h and then quenched in a preheated stainless steel/ graphite mould at a temperature of 300 °C - 600 °C and then cooled.
  • the prepared glass sample was annealed at 300 °C- 500 °C for 1 h and then cooled at the rate of 0.5 °C - 2 °C per minute to release the stress in the glass sample.
  • the prepared glass sample was cut into required size and shape using diamond cutter.
  • the code for the present sample is called as gFP2.
  • the powdered mixture was melted in a platinum doped with 10% Rhodium crucible and heated at the temperature of 1050 °C - 1400 °C for 1 - 4 h and then quenched in a preheated stainless steel/ graphite mould at a temperature of 300 °C - 600 °C then cooled.
  • the prepared glass sample was annealed at 300 °C- 500 °C for 1 h and then cooled at the rate of 0.5 °C - 2 °C per minute to release the stress in the glass sample.
  • the prepared glass sample was cut into required size and shape using diamond cutter.
  • the code for the present sample is called as MgFP3.
  • Example 4 The code for the present sample is called as MgFP3.
  • the powdered mixture was melted in platinum doped with 10% Rhodium crucible and heated at the temperature 1050 °C - 1400 °C for 1 - 4 h then quenched in a preheated stainless steel/ graphite mould of temperature 300 °C - 600 °C then cooled.
  • the prepared glass sample was annealed at 300 °C - 500 °C for 1 h then cooled at the rate of 0.5 °C - 2 °C per minute to release the stress in the glass sample.
  • the prepared glass sample was cut into required size and shape using diamond cutter.
  • the code for the present sample is called as MgFP4.
  • the powdered mixture was melted in platinum doped with 10% Rhodium crucible and heated at the temperature ranging from 1050 °C to 1400 °C for 1- 4 h and then quenched in a preheated stainless steel/ graphite mould at a temperature ranging from 300 °C to 600 °C and then cooled.
  • the prepared glass sample was annealed at 300 °C - 500 °C for 1 h then cooled at the rate of 0.5 °C - 2 °C per minute to release the stress in the glass sample.
  • the prepared glass sample was cut into required size and shape using diamond cutter.
  • the code for the present sample is called as MgFP5.
  • the density of the prepared glass samples was measured using Archimedes' principle
  • W b is the weight in water
  • p b is the density of water.
  • Ultrasonic velocities (U L , longitudinal and U s , shear) and attenuations (U L , longitudinal and U s , shear) measurements were carried out using pulse echo method and cross-correlation technique.
  • the measurement system consists of an ultrasonic process control system (model FUII050; Fallon Ultrasonics Inc. Ltd., ON, Canada), a 100-MHz digital storage oscilloscope (model 54600B; Hewlett Packard, Palo Alto, CA), and a computer.
  • the measurements were carried out by generating longitudinal and shear waves using X- and Y- cut transducers operated at a fundamental frequency of 5 MHz.
  • Elemental analysis of the prepared glass sample was done using X-ray photo electron spectroscopy (model AXIS Ultra DLD; Kratos, Kyoto, Japan) with Al Ka source operating at 210 W.
  • the glass sample was ground using planetary ball mill (model PM 100; Retsch, Haan, Germany) and the powdered glass sample was used for XPS analysis.
  • a survey spectrum (0-1200 eV) was recorded and high-resolution spectra for Cls and Nls band were obtained.
  • X-ray as the excitation radiation was used for the XPS measurements.
  • the spectra were collected in a fixed retarding ratio mode with bandpass energy of about 10 eV.
  • XRD studies were carried out on each glass sample.
  • An X-ray diffractometer (model PW 1700; Philips, Eindhoven, The Netherlands) was used with CuKa as a radiation source to obtain the XRD pattern in the range of a scanning angle between 20° and 80°.
  • the glass samples were removed from SBF solution after 21 days in vitro studies and then washed gently with double distilled water. The washed glass samples were dried at room temperature. The dried glass was subjected to obtain the XRD pattern as discussed above.
  • the prepared glass samples were soaked for 21 days in laboratory prepared SBF solution and kept in C0 2 incubator at the temperature of 37 °C in 6% C0 2 .
  • the variation in pH values of simulated body fluid (SBF) solutions was measured on all the 21 days using a pH meter (model 3-star; Thermo Orion, Beverly, MA) for all glasses under identical conditions.
  • the pH electrode was calibrated using the standard buffer solution with a pH value of 4.01, 7.00, and 10.01 before taking the measurements.
  • the percentage error in the measurement of pH is ⁇ 0.005.
  • the surface morphology of the prepared glass sample was analysed using SEM studies.
  • the glass samples were gently washed with double-distilled water and dried at room temperature.
  • a thin layer of a gold film was coated on the surface of glass sample using sputtering technique.
  • the SEM (model Ultra 55; Zeiss, Oberkochen, Germany) was used to obtain a surface image of all glass samples before and after in vitro studies to analyse their surface morphology.
  • EDS Energy dispersive X-ray spectrograph
  • Nontoxic nature of the selected glass sample was assessed using cytotoxicity study in cell culture lines.
  • Human gastric adenocarcinoma (AGS) cell line (ATCC-1739) was obtained from the National Centre for Cell Science, Pune, India. The cells were grown and maintained in Dulbecco's modified Eagle's medium (DMEM)/nutrient mixture F-12 HAM (1 : 1) with 2 mM L 1 glutamine supplemented with 10% fetal bovine serum, 45 IU ml 1 penicillin and 45 II) ml "1 streptomycin. Growth ingredients were also added and incubated in a humidified atmosphere at 37 °C in 5% C0 2 .
  • DMEM Dulbecco's modified Eagle's medium
  • F-12 HAM (1 : 1) with 2 mM L 1 glutamine supplemented with 10% fetal bovine serum, 45 IU ml 1 penicillin and 45 II) ml "1 streptomycin. Growth ingredients were also added and incubated in a humidified atmosphere at 37
  • the pure confluent AGS cell lines were obtained and cells at a density of 10 3 were used to evaluate the cytotoxicity at a concentration of 100 mg ml 1 for the selected bioactive glass samples.
  • the morphology of AGS cell lines was observed regularly under binocular inverted microscope.
  • MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
  • the percentage of cell viability from triplicates of the bioactive glass treated and non-treated cells was calculated using optical density (OD 590 nm) as follows:
  • the un-decalcified section of the implant was dried at room temperature using desiccator.
  • a thin layer of a gold film was coated on the surface of glass sample using sputtering technique.
  • SEM and EDS studies were done on the dried slice to find the formation of HAp at the glass-bone interface.
  • Calcein fluorescence was used to examine the newly formed bone using a confocal laser scanning microscope (model : LSM 510 META; Zeiss, Gottingen, Germany). The excitation wavelength was set at 488nm (Ar laser). Calcein fluorescence was detected through a BP 515 -565 nm bandpass filter. Details obtained from the Figures:
  • Fig. 1 illustrates the protocol used for the synthesis of magnesium added fluorophosphate glass samples with different contents of fluorine.
  • the density variation of the prepared fluorophosphate glass samples as a function of added MgO content is shown in Fig. 2.
  • a sudden increase in the density from 2628.3 kgm 3 to 2659.9 kgm "3 due to the initial addition of MgO is noted.
  • a decrease in the density value to 2636 kgm "3 is noted for 2.0 mol% of MgO content.
  • Further addition of MgO leads to small increase of the density value to 2643 kgm "3 for 4.0 mol% of MgO content. Beyond this, a negligible change in the density value to is noted with the further addition of MgO content.
  • the observed behaviour explains the alteration of glass network by fluorine atom.
  • 3a and 3b shows the variation of elastic moduli of all the prepared glass samples as a function of MgO content.
  • Elastic moduli such as longitudinal, shear, young's and bulk modulus shows the same trend with the density variations during the addition of MgO content.
  • the glass containing 6.0 mol% of MgO showed the maximum moduli value than the other MgO added fluorophosphate glasses.
  • Fig. 4 shows the elemental composition of the glass sample MgFP5 using XPS.
  • SEM image of the prepared glass sample MgFP5 is showed in Fig. 5.
  • the smooth surface of the glass sample MgFP5 obtained from SEM image exhibits the amorphous nature of the sample.
  • Fig.6 shows EDS spectrograph of the glass sample MgFP5. A close agreement is noted between experimental and nominal composition of the glass sample MgFP5.
  • Fig. 5 and Fig. 6 confirm the presence of magnesium oxide and fluorine atoms in the glass network.
  • FTIR spectrograph of all the prepared glass samples after in vitro studies is shown in the Fig. 8.
  • the FTIR absorption assignment band at 478 cm “1 , 530 cm “1 , 740 cm “1 , 870 cm “1 , 1016 cm “1 , 1100 cm “1 , 1275 cm “1 , 3430 cm “1 are respectively of vibration bands of P0 4 3 ⁇ , HAp, P-O-P (symmetric mode), C-O, P-0 (stretching mode), «r-Ca 2 P 2 0 7 , P0 2 (asymmetric mode), and water associated in HAp.
  • the presence of HAp confirms the bone bonding ability of all the glass samples.
  • XRD patterns of all the glass after in vitro studies are shown in Fig. 9.
  • a weak one at 65.58° in the sample MgFP5 shows respectively the rich concentration of HAp and Weak concentration of FAp.
  • Fig. 10 shows the SEM image of the glass sample MgFP5 after in vitro studies.
  • the SEM image confirms the rich deposit of Ca-P layer on MgFP5 glass surface.
  • the size of the deposited particles is in the order of 20-100 nm.
  • Fig. 11 shows the elemental composition of the deposited precipitate using EDS.
  • the Ca/P ratio of the deposit is about 1.6 indicating the deposit is HAp.
  • the presence of fluorine molecules in the surface precipitate confirms the existence of fluoroapatite.
  • the EDS spectrograph clearly indicates the presence of hydroxyapatite and fluoroapatite on the surface of the glass sample MgFP5.
  • Fig. 12 shows the optical microscope image of cell viability test for the sample MgFP5. The image clearly shows there is no cytotoxicity observed in the glass sample MgFP5.
  • Fig. 13a shows the SEM image at 100X magnification of un-decalcified section of the femoral condyle of the rabbit after 10 weeks of glass implanting. There is a definitive distinct layer of transformations all around the glass where it was in contact with the bone.
  • Fig. 13B shows the SEM image at 1000X magnification where the distinctive interface between bone and glass is well seen and it proves the bond the glass has made with the bone.
  • Fig.14 shows EDS spectrograph of the interface The molecular pattern clearly establishes the formation of Hap layer.
  • Fig. 15 shows the magnified view of the bone and the newly formed interface.
  • Ar laser When illuminated by Ar laser, there is brilliant fluorescence over the ring of the bone and interface.
  • active apatite formation On super imposition of both it is clearly made out active apatite formation has extended to a depth of 519 pm in the glass form the periphery confirming the bioconversion of magnesium added fluorophosphate glass.

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Abstract

L'invention concerne différentes compositions de verres de fluorophosphate contenant du magnésium préparées par un procédé de fusion-trempe. La conversion physico-chimique et biologique des verres de fluorophosphate contenant du magnésium est étudiée par des mesures de densité, des mesures ultrasonores pour déterminer les modules élastiques, les formes par diffraction des rayons X, les spectres FTIR, le spectrographe XPS, les variations de pH pendant 21 jours d'études in vitro en solution SBF, images SEM et spectres EDS. La bioconversion est également étudiée par des analyses in vivo d'implantation du verre optimisé dans un os animal pendant 10 semaines avant images SEM, spectres EDS et images CLSM. Le résultat obtenu avant et après les études in vitro et in vivo est analysé en termes de structure, de stabilité, de propriétés mécaniques, de capacité à se lier à l'os et de bioconversion des échantillons de verre préparés. L'échantillon de MgFp5 s'avère idéal et meilleur que les autres échantillons pour une utilisation clinique ultérieure.
PCT/IN2014/000760 2013-12-20 2014-12-09 Bioconversion de verres de fluorophosphate contenant du magnésium et procédé de fabrication associé WO2015092815A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115996767A (zh) * 2020-02-26 2023-04-21 骨头替代物公司 一种作为骨移植物的合成复合材料及其方法

Citations (2)

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Publication number Priority date Publication date Assignee Title
DE4113021A1 (de) * 1991-04-20 1992-10-22 Carus Carl Gustav Resorbierbare phosphatglaeser und resorbierbare phosphatglaskeramiken und verfahren zu ihrer herstellung
WO2013093101A1 (fr) * 2011-12-23 2013-06-27 Queen Mary And Westfield College Composition de fabrication d'un ciment ou d'un implant

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4113021A1 (de) * 1991-04-20 1992-10-22 Carus Carl Gustav Resorbierbare phosphatglaeser und resorbierbare phosphatglaskeramiken und verfahren zu ihrer herstellung
WO2013093101A1 (fr) * 2011-12-23 2013-06-27 Queen Mary And Westfield College Composition de fabrication d'un ciment ou d'un implant

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ENSANYA A. ABOU NEEL ET AL: "Bioactive functional materials: a perspective on phosphate-based glasses", JOURNAL OF MATERIALS CHEMISTRY, vol. 19, no. 6, 1 January 2009 (2009-01-01), pages 690 - 701, XP055178396, ISSN: 0959-9428, DOI: 10.1039/B810675D *
K. FRANKS ET AL: "The effect of MgO on the solubility behavior and cell proliferation in a quaternary soluble phosphate based glass system", JOURNAL OF MATERIALS SCIENCE: MATERIALS IN MEDICINE, vol. 13, no. 6, 1 January 2002 (2002-01-01), pages 549 - 556, XP055184290, ISSN: 0957-4530, DOI: 10.1023/A:1015122709576 *
KNOWLES J C: "Phosphate based glasses for biomedical application", JOURNAL OF MATERIALS CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 13, 14 August 2003 (2003-08-14), pages 2395 - 2401, XP002633096, ISSN: 0959-9428, [retrieved on 20030814], DOI: 10.1039/B307119G *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115996767A (zh) * 2020-02-26 2023-04-21 骨头替代物公司 一种作为骨移植物的合成复合材料及其方法

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