Porous biomaterials surface activation method

• US 8,216,630 B2
• Filed: 06/18/2009
• Issued: 07/10/2012
• Est. Priority Date: 06/18/2009
• Status: Expired due to Fees

• Current Assignee: Teknimed SA
• Original Assignee: Institut National Polytechnique de Toulouse, Teknimed SA
• Inventors: Rey, Christian, Autefage, Hélène, Cazalbou, Sophie, Combes, Christèle
• Primary Examiner(s): Meeks, Timothy
• Assistant Examiner(s): Sellman, Cachet
• Application Number:
  US12/487,101
• Publication Number:
  US 20100323094A1
• Time in Patent Office: 1,118 Days
• Field of Search: 427/2.1, 427 224- 229, 424/422, 424/423, 424/602
• US Class Current: 427/2.1
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/32 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C04B 2111/00836 for medical or dental applications
• CPC Class Codes: C04B 35/447 based on phosphates , e.g. hydroxyapatite
• CPC Class Codes: C04B 38/00 Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof treating slag with gases or gas generating material C04B5/06 ; expanded graphite C04B35/536
• CPC Class Codes: C04B 41/009 characterised by the material treated
• CPC Class Codes: C04B 41/4539 as a emulsion, dispersion or suspension
• CPC Class Codes: C04B 41/4549 Nanometer-sized particles
• CPC Class Codes: C04B 41/5048 Phosphates
• CPC Class Codes: C04B 41/87 Ceramics

Abstract

The present invention relates to a porous biomaterials surface activation method by coating with a layer of apatitic nanocrystals in order to increase their surface reactivity. The method according to the invention is characterized by the following steps: a) preparing a nanocrystalline apatitic calcium phosphate analogous to bone mineral by mixing a calcium salt solution with a phosphate salt solution in a Ca/P ratio ranging between 1.3 and 2 at a temperature ranging between 0 and 60 ° C., b) slurrying the mixture obtained in step a) in an aqueous solution so as to obtain a fluid, homogeneous paste containing 80 to 98% of water, c) bringing a porous biomaterial into contact with the suspension obtained in step b), d) drying the porous biomaterial at a temperature below 100 ° C.

Claims

1. Porous biomaterials surface activation method wherein it comprises the following steps:

a) preparing a nanocrystalline apatitic calcium phosphate analogous to bone mineral by mixing a calcium salt solution with a phosphate salt solution in a Ca/P ratio ranging between 1.3 and 2 at a temperature ranging between 0 and 60 °

C.,

b) slurrying the mixture obtained in step a) in an aqueous solution so as to obtain an aqueous suspension comprising a fluid, homogeneous paste containing 80 to 98% of water,

c) contacting a porous biomaterial with the suspension obtained in step b),

d) drying the porous biomaterial at a temperature below 100 °

C.

2. Method according to claim 1, wherein the mixture obtained once step a) is completed undergoes a treatment to modify the surface of the nanocrystals by bringing it into contact with at least one compound exhibiting a biological activity and/or modifying the surface properties of the nanocrystals, said compound being selected from the group consisting of a mineral ion, an organic molecule, and mixture thereof.

3. Method according to claim 1, wherein the biomaterial obtained once step d) is completed undergoes a surface treatment by bringing it into contact with at least one compound exhibiting a biological activity and/or modifying the surface properties of the nanocrystals, said compound being selected from the group consisting of a mineral ion, an organic molecule, and mixture thereof.

4. Method according to claim 2, wherein the surface treatment is carried out by ion exchange with an aqueous solution containing at least one ion selected from the group consisting of Mg²⁺, Sr²⁺, Mn²⁺, SiO₄⁴⁻

, VO₄³⁻

, and mixtures thereof.

5. Method according to claim 2, wherein the surface treatment is carried out by adsorption of at least one organic molecule selected from the group consisting of growth factors, antibiotics, and mixtures thereof.

6. Method according to claim 1, wherein the mixture obtained once step a) is completed has a Ca/P ratio ranging between 1.33 and 1.67.

7. Method according to claim 1, wherein prior to step c), the biomaterial is cleared of any organic impurity that could hinder wetting by the aqueous suspension by prior heating in air at a temperature of about 900 °

C. for 3 to 5 minutes, or by ozonization treatment.

8. Method according to claim 1, wherein step c) is carried out by immersion of the biomaterial in the solution obtained in step b) or by spraying or coating the solution obtained in step b) on the biomaterial.

9. Method according to claim 8, wherein step c) is carried out under partial vacuum with a pressure ranging between 10 to 30 mm Hg.

10. Method according to claim 1, wherein, prior to step d), the biomaterial obtained at the end of step c) is partially and progressively dehydrated.

11. Method according to claim 1, wherein steps b), c) and d) are repeated.

12. Method according to claim 1, wherein the biomaterial is a phosphocalcic ceramic.

13. Method according to claim 2, wherein the biomaterial obtained once step d) is completed undergoes a surface treatment by bringing it into contact with at least one compound exhibiting a biological activity and/or modifying the surface properties of the nanocrystals, said compound being selected from the group consisting of a mineral ion, an organic molecule, and mixture thereof.

14. Method according to claim 3, wherein the surface treatment is carried out by ion exchange with an aqueous solution containing at least one ion selected from the group consisting of Mg²⁺, Sr²⁺, Mn²⁺, SiO₄⁴⁻

, VO₄³⁻

, and mixtures thereof.

15. Method according to claim 3, wherein the surface treatment is carried out by adsorption of at least one organic molecule selected from the group consisting of growth factors, antibiotics, and mixtures thereof.

16. Method according to claim 4, wherein the surface treatment is carried out by adsorption of at least one organic molecule selected from the group consisting of growth factors, antibiotics, and mixtures thereof.

17. Method according claim 2, wherein the mixture obtained once step a) is completed has a Ca/P ratio ranging between 1.33 and 1.67.

18. Method according claim 3, wherein the mixture obtained once step a) is completed has a Ca/P ratio ranging between 1.33 and 1.67.

19. Method according claim 4, wherein the mixture obtained once step a) is completed has a Ca/P ratio ranging between 1.33 and 1.67.

20. Method according claim 5, wherein the mixture obtained once step a) is completed has a Ca/P ratio ranging between 1.33 and 1.67.

21. Method according to claim 2, wherein prior to step c), the biomaterial is cleared of any organic impurity that could hinder wetting by the aqueous suspension by prior heating in air at a temperature of about 900 °

C. for 3 to 5 minutes, or by ozonization treatment.