Resorbable macroporous bioactive glass scaffold and method of manufacture

Abstract

A method of manufacturing a resorbable, macroporous bioactive glass scaffold comprising approximately 24-45% CaO, 34-50% SiO.sub.2, 0-25% Na.sub.2O, 5-17% P.sub.2O.sub.5, 0-5% MgO and 0-1% CaF.sub.2 by mass percent, produced by mixing with pore forming agents and specified heat treatments.

Claims

1. A method of manufacturing a resorbable, macroporous bioactive glass scaffold comprising the steps of: creating a mixture consisting essentially of by mass percent about 24-45% CaO, 34-50% SiO.sub.2, 0-25% Na.sub.2O, 5-17% P.sub.2O.sub.5, 0-5% MgO and 0-1% CaF.sub.2; melting the mixture at a temperature ranging from about 1380 C. to 1480 C.; cooling, crushing and sieving the mixture to obtain glass powders having granularity of greater than 100 microns and up to 300 microns; adding into the glass powders by mass percent about 20-70% of at least one pore forming agent and about 1-5% of a 5-10% solution of polyvinyl alcohol adhesive to form a composition; pressing the composition of the glass powders, the at least one pore forming agent and the polyvinyl alcohol adhesive into dyes to produce shaped pellets under a pressure of approximately 2-20 MPa; and sintering the pellets under temperatures ranging from about 750 C. to about 900 C. for a period of about 1-5 hours, thereby manufacturing a resorbable, macroporous bioactive glass scaffold having interconnected pores.

2. The method of claim 1, wherein the granularity of the pore forming agents is chosen to be between about 50-600 microns.

3. The method of claim 1, wherein the at least one pore forming agent is chosen from the group of pore forming agents consisting of polyethylene glycol, polyvinyl alcohol, paraffin, and polystyrene-divinylbenzene.

4. A method of manufacturing a resorbable, macroporous bioactive glass scaffold comprising the steps of: creating a mixture consisting essentially of, by mass percent about 24-45% CaO, 34-50% SiO.sub.2, 0-25% Na.sub.2O, 5-17% P.sub.2O.sub.5, 0-5% MgO and 0-1% CaF.sub.2; melting the mixture at a temperature ranging from about 1380 C. to about 1480 C.; cooling, crushing and sieving the mixture to obtain glass powders having granularity of about 150-300 microns; adding into the 150-300 micron glass powders by mass percent about 20-70% of at least one pore forming agent and about 1-5% of a 5-10% solution of polyvinyl alcohol adhesive to form a composition; pressing the composition of the 150-300 micron glass powders, the at least one pore forming agent and the polyvinyl alcohol adhesive into dyes to produce shaped pellets under a pressure of about 2-20 MPa; and sintering the pellets under temperatures ranging from about 750 to about 900 C. for a period of about 1-5 hours, thereby manufacturing a resorbable, macroporous bioactive glass scaffold having interconnected pores.

5. The method of claim 4, wherein the granularity of the pore forming agents is chosen to be between about 50-600 microns.

6. The method of claim 4, wherein the at least one pore forming agent is chosen from the group of pore forming agents consisting of polyethylene glycol, polyvinyl alcohol, paraffin, and polystyrene-divinylbenzene.

7. The method of claim 1, wherein the manufactured resorbable, macroporous bioactive glass scaffold has porosity in the range from 40% to 80%.

8. The method of claim 1, wherein the glass powders in the manufactured resorbable, macroporous bioactive glass scaffold have pore size from 50 to 600 microns.

9. The method of claim 1, wherein the manufactured resorbable, macroporous bioactive glass scaffold has a compressive strength at 1-16 MPa.

10. The method of claim 1, wherein the manufactured resorbable, macroporous bioactive glass scaffold is capable of releasing soluble silicon ions with precipitation of bone-like hydroxyl-apatite crystallites on a surface of the scaffold, following immersion into simulated body fluids (SBF).

11. The method of claim 1, wherein the manufactured resorbable, macroporous bioactive glass scaffold has a degradation rate of approximately 2-30% following immersion into simulated body fluids (SBF) for 5 days.

12. The method of claim 4, wherein the manufactured resorbable, macroporous bioactive glass scaffold has porosity in the range from 40% to 80%.

13. The method of claim 4, wherein the glass powders in the manufactured resorbable, macroporous bioactive glass scaffold have pore size from 50 microns to 600 microns.

14. The method of claim 4, wherein the manufactured resorbable, macroporous bioactive glass scaffold has a compressive strength at 1-16 MPa.

15. The method of claim 4, wherein the manufactured resorbable, macroporous bioactive glass scaffold is capable of releasing soluble silicon ions with precipitation of bone-like hydroxyl-apatite crystallites on a surface of the scaffold, following immersion into simulated body fluids (SBF).

16. The method of claim 4, wherein the manufactured resorbable, macroporous bioactive glass scaffold has a degradation rate of approximately 2-30% following immersion into simulated body fluids (SBF) for 5 days.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a photograph of the prepared macroporous bioactive glass.

(2) FIG. 2 is an optical microscope picture displaying cross-sections of the macroporous bioactive glass.

(3) FIG. 3 shows XRD displays for the macroporous bioactive glass materials prepared under different temperatures; these illustrations show that different levels of crystallization of calcium silicate or calcium phosphate can be found on the surface of the materials prepared under different temperatures; (a) bioactive glass powder before sintering, (b) bioactive glass scaffolds prepared by sintering at 800 C., (c) bioactive glass scaffolds prepared by sintering at 850 C.

(4) FIG. 4(A) is an SEM picture of the macroporous bioactive glass material of this invention before being immersed in SBF (i.e. simulated body fluids); 4(B) is an SEM picture of the material immersed SBF for 1 day; 4(C) is an SEM picture of the material when immersed in SBF for over 3 days; these pictures show that substantial hydroxyapatite crystalline can form on the surface of the material when immersed in SBF for 1 day.

(5) FIG. 5 is a Fourier Transform Infrared spectrometry (FTIR) spectra of the macroporous bioactive glass materials before being immersed in SBF, as well as after being immersed in SBF for 0 hours, 6 hours, 1 day, 3 days and 7 days respectively; the resulting analysis reveals that the hydroxyl-apatite peak can be observed when such material has been immersed in SBF for only 6 hours.

DETAILED DESCRIPTION OF THE INVENTION

(6) The implementation of this invention is detailed as below:

(7) 1. Preparation of Materials:

(8) The bioactive glass powder in this invention is prepared using the melting method. The inorganic materials applied in the present invention are all of analytical purity. Specifically, these chemical reagents are weighed and evenly mixed in line with requirements for proper composition results, and then melted in temperatures ranging from 1380 C. to 1480 C. to produce glass powders with a granularity varying from 40 to 300 m after cooling, crushing and sieving procedures. Furthermore, such glass powders are then used as the main raw material to prepare a variety of the macroporous bioactive glass scaffold substances by way of different processing technologies. The pore forming agents specified in the present invention can be organic or polymer materials such as polyethylene glycol, polyvinyl alcohol, paraffin and polystyrene-divinylbenzene, etc., whose granularity can fall in the range of 50-600 microns. Thus, the pore forming agent within a certain granularity range (20-70% in mass percent) can be blended with the said bioactive glass powders and the resulting mixture can be molded by adopting either of the following two approaches:

(9) First, the dry pressing molding approach, in which 1-5% polyvinyl alcohol (concentration at 5-10%) is added to the said mixture as the adhesive, which is stirred, and then dry-pressed into a steel mold (pressure at 2-20 Mpa) to produce a pellet of the macroporous material, which is then sintered (temperature at 750-900 C.) for 1-5 hours to obtain final product.

(10) Second, the gelation-casting approach, in which an aqueous solution is prepared as per the following mass percent concentrations: 20% acrylamide, 2% N, N-methylene-bis-acrylamide cross-linking agents and 5-10% polyacrylic acid dispersant agents. Next, the aforementioned mixture and the aqueous solution (volume percent at 30-60%) is combined and mixed, and ammonium persulfate (1-5% in mass percent) and N, N,N, N-tetramethyl ethylene diamine (1-5% in mass percent) is added. Then, the above-mentioned materials are stirred to produce a slurry with fine fluidity and homogeneity, which is then poured into plastic or plaster molds for gelation-casting. Later the cross-linking reaction of monomers is induced under temperatures ranging from 30 C. to 80 C. for 1-10 hours, and pellets of the macroporous material are obtained after a few hours of drying at 100 C. The pellets are processed first at the temperature of 400 C. to remove organics, and then sintered at 750-900 C. to obtain the macroporous material of the present invention.

(11) 2. Performance Evaluation

(12) 2.1. The Mechanical Strength of the Macroporous Material:

(13) An array of samples obtained in this invention was tested for their respective compressive strengths using the Autograph AG-I Shimadzu Computer-Controlled Precision Universal Tester made by the Shimadzu Corporation. The testing speed designated for these samples was 5.0 mm/min. This test revealed that the compressive strength of the macroporous material obtained in this invention can be well controlled within the scope of 1-16 MPa.

(14) 2.2. The Porosity of the Macroporous Materials

(15) The Archimedes Method was used to carry out a test with a part of the samples mentioned above to determine their porosities, and a Scanning Electron Microscope (SEM) was used to observe their pore shapes and distribution. This test demonstrated that the porosity of the macroporous material obtained in this invention can be well controlled within a range of 40-80%.

(16) 2.3 Bioactivity Evaluation

(17) A test of in vitro solution bioactivity was carried out with the macroporous materials obtained in the present invention, after being washed in de-ionized water and acetone successively, and then air dried afterwards. The solution applied was simulated body fluids (SBF). The ion and ionic group concentrations in this SBF are the same as those in human plasma. This SBF's composition is as below: NaCl: 7.996 g/L NaHCO.sub.3: 0.350 g/L KCl: 0.224 g/L K.sub.2HPO.sub.4.3H.sub.2O: 0.228 g/L MgCl.sub.2.6H.sub.2O: 0.305 g/L HCl: 1 mol/L CaCl.sub.2: 0.278 g/L Na.sub.2SO.sub.4: 0.071 g/L NH.sub.2C(CH.sub.2OH).sub.3: 6.057 g/L

(18) The test was carried out with macroporous material immersed in SBF in the following conditions: 0.15 g of macroporous material, 30.0 ml/day SBF, 37 C. in a temperature-controlled water-bath. After the macroporous material was immersed in SBF for a period of 1, 3 or7 days respectively, samples were taken out and washed using ion water, and then underwent the SEM, Fourier Transform Infrared spectrometry (FTIR) and XRD tests. The respective results of the tests can be seen in FIGS. 3, 4 and 5. The relevant bioactivity experiment results have shown that the macroporous glass scaffold materials obtained in the present invention can induce the formation of bone-like hydroxyapatite on their surface, indicating ideal bioactivity of these materials.

(19) 2.4 Degradability Evaluation

(20) A bioactivity experimental test was conducted on the macroporous materials in this invention after being washed in de-ionized water and acetone successively, and then dried. Evaluation of both degradation speed and degradability of the macroporous materials according to the content of SiO.sub.2 substances that are released at different time points after the materials have been immersed in SBF was conducted. For example, where PEG is used as the pore forming agent, the macroporous bioactive glass scaffolds (porosity at 40%) obtained after the processes of dry pressing molding and calcination (temperature at 850 C.) exhibit a degradability of 10-20% when the scaffold has been immersed in SBF for 5 days.

Implementation Example 1

(21) The raw materials used in this example are the same as those described above.

(22) SiO.sub.2, Na.sub.2CO.sub.3, CaCO.sub.3 and P.sub.2O.sub.5 (all of analytical purity) are mixed proportionally, and the mixture is melted into homogenous fused masses at the temperature of 1420 C. and then cooled, crushed and sieved to obtain bioactive glass powder with a particle diameter ranging from 40-300 microns. The composition of the bioactive glass powder is expressed as CaO 24.5%, SiO.sub.2 45%, Na.sub.2O 24.5% and P.sub.2O.sub.5 6%. Next, the bioactive glass powder (150-200 microns in granularity) is mixed with the polyethylene glycol powder (200-300 microns in granularity) at a mass percent of 60:40. Polyvinyl alcohol solution (6%), which serves as the adhesive, is added and the solution is mixed. The mixture is then dry-pressed under a pressure of 14 MPa, and the pellets of the macroporous materials are stripped from the mold. The pellets are first processed at 400 C. to remove organics, and then sintered at 850 C. for 2 hours to obtain the said macroporous materials with a compressive strength at approx. 1.25 MPa and a porosity at about 56%. The XRD indicates the existence of both the Ca.sub.4P.sub.2O.sub.9 and CaSiO.sub.3, as shown in FIG. 2(C).

(23) Finally, the said macroporous materials are immersed in simulated body fluids (SBF) for periods of 6 hours and 1, 3, and 7 days respectively, and evaluated as to both bioactivity and resorbability/degradability. Results in FIGS. 4 and 5 demonstrate that the macroporous glass material of this invention has strong bioactivity, as a bone-like apatite layer is soon formed on the surface of such materials after they are immersed in SBF. After this material has been immersed in SBF for 5 days, its degradation rate can be up to a level of 14%, suggesting that the macroporous bioactive glass material in this invention has ideal degradability, and can therefore be expected to be successfully applied for the restoration of injured hard tissues and as the cell scaffold for in vitro culture of bone tissue.

Implementation Example 2

(24) SiO.sub.2, CaCO.sub.3, Ca.sub.3 (PO4).sub.2, MgCO.sub.3, CaF.sub.2 (all of analytical purity) are mixed proportionally, melted into a homogenous fused masses at the temperature of 1450 C., and then cooled, crushed and sieved to obtain bioactive glass powder (particle diameter ranging from 40-300 microns). The composition of the bioactive glass powder is CaO 40.5%, SiO.sub.2 39.2%, MgO 4.5%, P.sub.2O.sub.5 15.5% and CaF.sub.2 0.3%.

(25) Next, the bioactive glass powder is blended with polyvinyl alcohol powder (300-600 microns in granularity) at a mass percent of 50:50 to obtain a solid mixture. An aqueous solution composed of 20% acrylamide, 2% N,N-Methylene-bis-acrylamide and 8% polyacrylic acid is prepared, and 10 grams of the said solid mixture is blended with the aqueous solution at a volume percent (ratio) of 50:50, with several drops of ammonium persulfates (3% in mass percent) and several drops of N,N,N,N-tetramethyl ethylene diamine (3% in mass percent) added and stirred to produce a slurry with fine fluidity, which is poured into molds for gelation-casting. The cross-linking reaction of monomers of the material is induced for 3 hours at 60 C. In this way, pellets of the macroporous material are obtained by stripping them from the mold after the gelation-casts have been dried at 100 C. for 12 hours. Subsequently, the pellets are processed at 400 C. to remove organics, and then sintered at 850 C. for 2 hours to produce the macroporous materials that feature a compressive strength at about 6.1 MPa and porosity at approx. 55%. This material demonstrated degradability is 78% (calculated based on the mass percent of Si releasing) after being immersed in Simulated Body Fluids for 3 days.

Implementation Example 3

(26) The raw materials and the preparation methods of the bioactive glass powder used in this example are the same as those in Implementation Example 2.

(27) The bioactive glass powder (granularity at 150-200 microns) is blended with PEG powder (granularity at 200-300 microns) at the mass ratio of 40:60. Polyvinyl alcohol solution (concentration at 6%) is added to serve as the adhesive and mixed. This mixture is dry-pressed under a pressure of 14 MPa, and pellets of the macroporous materials are obtained by removal from the mold. The pellets are first processed at 400 C. to remove organics, and then sintered at 800 C. to obtain the said macroporous materials with a compressive strength at approx. 1.5 MPa and porosity at about 65%. After being immersed in Simulated Body Fluids for 3 days, the degradation rate of the macroporous glass material is 38% (calculated based on the mass percent of Si releasing).

(28) It is understood and contemplated that equivalents and substitutions for certain elements and steps set forth above may be obvious to those skilled in the art, and therefore the true scope and definition of the invention is to be as set forth in the following claims.