Resorbable ceramics with controlled strength loss rates

• US 9,795,716 B2
• Filed: 04/09/2015
• Issued: 10/24/2017
• Est. Priority Date: 04/25/2006
• Status: Active Grant

• Current Assignee: Washington State University
• Original Assignee: Washington State University
• Inventors: Bose, Susmita, Bandyopadhyay, Amit
• Primary Examiner(s): Liu, Tracy
• Application Number:
  US14/682,343
• Publication Number:
  US 20150352248A1
• Time in Patent Office: 929 Days
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/12 for dental implants or prostheses
• CPC Class Codes: A61L 27/10 Ceramics or glasses
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/306 Other specific inorganic materials not covered by A61L27/303 - A61L27/32
• CPC Class Codes: A61L 27/32 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C04B 2235/3201 Alkali metal oxides or oxide-forming salts thereof
• CPC Class Codes: C04B 2235/3206 Magnesium oxides or oxide-forming salts thereof
• CPC Class Codes: C04B 2235/3208 Calcium oxide or oxide-forming salts thereof, e.g. lime
• CPC Class Codes: C04B 2235/3212 Calcium phosphates, e.g. hydroxyapatite
• CPC Class Codes: C04B 2235/3213 Strontium oxides or oxide-forming salts thereof
• CPC Class Codes: C04B 2235/3232 Titanium oxides or titanates, e.g. rutile or anatase
• CPC Class Codes: C04B 2235/3272 Iron oxides or oxide forming salts thereof, e.g. hematite, magnetite
• CPC Class Codes: C04B 2235/3281 Copper oxides, cuprates or oxide-forming salts thereof, e.g. CuO or Cu2O
• CPC Class Codes: C04B 2235/3284 : Zinc oxides, zincates, cadmium oxides, cadmiates, mercury oxides, mercurates or oxide forming salts thereof
• CPC Class Codes: C04B 2235/3291 : Silver oxides
• CPC Class Codes: C04B 2235/34 : Non-metal oxides, non-metal mixed oxides, or salts thereof that form the non-metal oxides upon heating, e.g. carbonates, nitrates, (oxy)hydroxides, chlorides
• CPC Class Codes: C04B 2235/3418 : Silicon oxide, silicic acids or oxide forming salts thereof, e.g. silica sol, fused silica, silica fume, cristobalite, quartz or flint
• CPC Class Codes: C04B 2235/442 : Carbonates
• CPC Class Codes: C04B 2235/445 : Fluoride containing anions, e.g. fluosilicate
• CPC Class Codes: C04B 2235/5445 : submicron sized, i.e. from 0,1 to 1 micron
• CPC Class Codes: C04B 2235/608 : Green bodies or pre-forms with well-defined density
• CPC Class Codes: C04B 2235/77 : Density
• CPC Class Codes: C04B 2235/786 : Micrometer sized grains, i.e. from 1 to 100 micron
• CPC Class Codes: C04B 2235/80 : Phases present in the sintered or melt-cast ceramic products other than the main phase
• CPC Class Codes: C04B 2235/96 : Properties of ceramic products, e.g. mechanical properties such as strength, toughness, wear resistance
• CPC Class Codes: C04B 35/447 : based on phosphates , e.g. hydroxyapatite
• CPC Class Codes: C04B 35/6261 : Milling

Abstract

Particular aspects of the present disclosure provide bio-resorbable and biocompatible compositions for bioengineering, restoring, or regenerating tissue or bone. In one embodiment, a biocompatible composition includes a three-dimensional porous or non-porous scaffold material comprising a calcium phosphate-based ceramic having at least one dopant therein selected from metal ion dopants or metal oxide dopants. The composition is sufficiently biocompatible to provide for a cell or tissue scaffold, and resorbable at a controlled resorption rate for controlled strength loss under body, body fluid or simulated body fluid conditions.

Claims

1. A bioresorbable and biocompatible composition for bioengineering, restoring, or regenerating a target tissue or musculoskeletal tissue, comprising:

a three-dimensional scaffold material comprising a plurality of calcium phosphate containing ceramic particles interconnected to form a porous network between and among the ceramic particles, the individual calcium phosphate-containing ceramic particles having;

a calcium phosphate material having a formula (Ca_x(PO₄)_y, where x=1 or more, and y=1 or more), or hydroxylated variants thereof; and

at least one dopant forming a single phase with the calcium phosphate material, the dopant being selected from the group consisting of ZnO, NaF, KF, FeO, Fe₂O₃, SrO, CuO, SiO₂, TiO₂, Ag₂O and CaCO₃, the dopant having a concentration sufficient to render the scaffold material resorbable at a target resorption rate under a body, body fluid or simulated body fluid condition, thereby achieving a target mechanical strength and target strength degradation of the scaffold material under the body, body fluid or simulated body fluid conditions.

2. The composition of claim 1, wherein the at least one dopant is present in a single-element or multi-element amount between 0 and about 10 wt %, from about 0.5 to about 5 wt %, from about 1 to about 3 wt %, from about 2 to about 7 wt %, from about 3 to about 7 wt %, or from about 4 to about 7 wt %.

3. The composition of claim 1, wherein biocompatibility comprises biocompatibility with respect to at least one cell or tissue type selected from the group consisting of eukaryotic cells, mammalian cells, bone forming or restructuring cells, osteoplastic or osteoplastic precursor cells, cartilage cells, muscle cells, stem cells, differentiated stem cells, bone marrow stem cells, and nerve cells.

4. The composition of claim 1, wherein the tissue comprises at least one selected from the group consisting of bone, cartilage, muscle and musculoskeletal tissue.

5. The composition of claim 2, wherein the at least one dopant is present in an amount sufficient to maintain the compressive strength of the material at about 30% of original or higher, 40% of original or higher, 50% of original or higher, 60% of original or higher, 70% of original or higher, 80% of original or higher, or 90% of original or higher, in each case, for a period of at least 6, at least 7, least 8, at least 9, at least 10, at least 11 or at least 12 months under body, body fluid or simulated body fluid conditions, to provide for a slow-degrading composition.

6. The composition of claim 2, wherein the at least one dopant is present in an amount sufficient to reduce the compressive strength of the material to about 90%, or less than 90%, 80%, or less than 80%, 70%, or less than 70%, 60%, or less than 60% or 50%, or less than 50% of original, in each case, within a period of about 3 months, about 4 months, about 5 months or about 6 months under body, body fluid or simulated body fluid conditions, to provide for a fast-degrading composition.

7. The composition of claim 2, wherein the at least one dopant is selected from the group consisting of SrO, ZnO, TiO₂, and SiO₂ dopants, present in a single-element or multi-element amount between 0 and about 10 wt %, from about 0.5 to about 5 wt %, from about 1 to about 3 wt %, from about 2 to about 7 wt %, from about 3 to about 7 wt %, from about 4 to about 7 wt %.

8. The composition of claim 1, wherein the ceramic comprises a multi-element dopant comprising at least two dopants selected from the group consisting of Zn²⁺, Si²⁺, Na⁺, K⁺, Sr²⁺, Fe³⁺/Fe²⁺, Ti⁴⁺, Co₃²⁻

, ZnO, NaF, KF, FeO, Fe₂O₃, SrO, CuO, SiO₂, TiO₂, Ag₂O and CaCO₃, present in a single-element or multi-element amount between 0 and about 10 wt %, from about 0.5 to about 5 wt %, from aboutl to about 3 wt %, from about 2 to about 7 wt %, from about 3 to about 7 wt %, from about 4 to about 7 wt %.

9. The composition of claim 1, wherein the ceramic comprises at least one dopant ions and/or oxides present in a single-element or multi-element amount between 0 and about 10 wt %, from about 0.5 to about 5 wt %, from aboutl to about 3 wt %, from about 2 to about 7 wt %, from about 3 to about 7 wt %, from about 4 to about 7 wt %.

10. The composition of claim 1, wherein the calcium phosphate material comprises at least one single or mixed phase calcium phosphate material.

11. The composition of claim 1, wherein the calcium phosphate comprises at least one single or mixed phase calcium phosphate material having calcium to phosphate ratio (Ca/P) in a range from about 1.4:

1 to about 1.7;

1, or from about 1.0;

1 to about 2.0;

1.

12. The composition of claim 11, wherein the calcium to phosphate ratio is about 1.5:

1, or about 1.67;

1.

13. The composition of claim 1, wherein the calcium phosphate containing ceramic comprises at least one of tricalcium phosphate (TCP;

Ca₃(PO₄)₂) and Hydroxyapatite (Hap;

Ca₁₀(PO₄)₆(OH)₂).

14. The composition of claim 1, wherein the porous network has pore sizes in the range of about 10 nm to about 5 mm, or from about 10 nm to about 500 μ

m, or from about 1 nm to about 1 μ

m.

15. The composition of claim 1, wherein the scaffold material comprises dense to solid structures, or porous structures having internal cavities with sizes varying from nano-scale to larger sizes, or micro porous structures, wherein a core of the scaffold material is comprised of a geometric pattern of material with voided areas or low density structures with a quasi-solid exterior.

16. The composition of claim 1, further comprising at least one chemical, drug, growth factor or biological agent deposited, incorporated into, or stored within and/or on a surface of the scaffold material or within one or more pores thereof to operatively provide for release, controlled release or burst release of the agent to facilitate bioengineering, restoring or regenerating bone or other tissue.

17. The composition of claim 16, wherein the at least one agent comprises at least one selected from the group consisting of antibiotics, antimicrobial agents, growth factors, osteoinductive growth factors, drugs, polypeptides and proteins.

18. The composition of claim 17, wherein the at least one agent can be selectively activated and/or released at set times by the application of at least one chemical, electrical, magnetic or photochemical triggering event.

19. A bioresorbable and biocompatible composition for bioengineering, restoring, or regenerating a target tissue or musculoskeletal tissue, comprising:

a three-dimensional scaffold material comprising a plurality of calcium phosphate containing ceramic participles interconnected to form a porous network between and among the ceramic particles, the individual calcium phosphate containing ceramic particles having a calcium phosphate material with a formula (Ca_x(PO₄)_y, where x=1 or more, and y=1 or more), or hydroxylated variants thereof and at least one dopant forming a single phase with the calcium phosphate material, the dopant being selected from the group consisting of NaF, CaO, SiO₂, TiO₂, and Ag₂O, the dopant having a concentration sufficient to render the scaffold material resorbable at a target resorption rate under a body, body fluid or simulated body fluid condition, thereby achieving a target mechanical strength and target strength degradation of the scaffold material under the body, body fluid or simulated body fluid conditions.

20. The composition of claim 19, wherein the at least one dopant is present in a single-element or multi-element amount between 0 and about 10 wt %, from about 0.5 to about 5 wt %, from about 1 to about 3 wt %, from about 2 to about 7 wt %, from about 3 to about 7 wt %, or from about 4 to about 7 wt %.

21. The composition of claim 19, wherein the at least one dopant includes a multi-element dopant having NaF, CaO, Ag₂O, and TiO₂ at a concentration between 0 and about 10 wt %, between about 0.5 to about 5 wt %, between about 1 to about 3 wt %, between about 2 to about 7 wt %, between about 3 to about 7 wt %, or between about 4 to about 7 wt %.

22. The composition of claim 19, wherein the at least one dopant includes at least one of NaF, CaO, Ag₂O, or TiO₂ at a concentration between 0 and about 10 wt %, between about 0.5 to about 5 wt %, between aboutl to about 3 wt %, between about 2 to about 7 wt %, between about 3 to about 7 wt %, or between about 4 to about 7 wt %.

23. The composition of claim 19, wherein the calcium phosphate comprises at least one single or mixed phase calcium phosphate material having calcium to phosphate ratio (Ca/P) in a range from about 1.4:

1 to about 1.7;

1, or from about 1.0;

1 to about 2.0;

1.