Composition and method for self-assembly and mineralizatin of peptide amphiphiles

• US 20060149036A1
• Filed: 11/12/2003
• Published: 07/06/2006
• Est. Priority Date: 11/12/2002
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Stupp, Samuel I., Hartgerink, Jeffrey D., Beniash, Elia
• Granted Patent: US 7,554,021 B2
• Time in Patent Office: Days
• US Class Current: 530/350
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: Y10S 977/705 Protein or peptide
• CPC Class Codes: Y10S 977/722 On a metal substrate
• CPC Class Codes: Y10T 428/12583 Component contains compound of adjacent metal
• CPC Class Codes: Y10T 428/12639 Adjacent, identical composition, components
• CPC Class Codes: Y10T 428/24124 Fibers
• CPC Class Codes: Y10T 428/25 Web or sheet containing structurally defined element or component and including a second component containing structurally defined particles
• CPC Class Codes: Y10T 428/254 Polymeric or resinous material
• CPC Class Codes: Y10T 428/26 Web or sheet containing structurally defined element or component, the element or component having a specified physical dimension
• CPC Class Codes: Y10T 428/2991 Coated

Abstract

The present invention is directed to a composition useful for making homogeneously mineralized self assembled peptide-amphiphile nanofibers and nanofiber gels. The composition is generally a solution comprised of a positively or negatively charged peptide-amphiphile and a like signed ion from the mineral. Mixing this solution with a second solution containing a dissolved counter-ion of the mineral and/or a second oppositely charged peptide amphiphile, results in the rapid self assembly of the peptide-amphiphiles into a nanofiber gel and templated mineralization of the ions. Templated mineralization of the initially dissolved mineral cations and anions in the mixture occurs with preferential orientation of the mineral crystals along the fiber surfaces within the nanofiber gel. One advantage of the present invention is that it results in homogenous growth of the mineral throughout the nanofiber gel. Another advantage of the present invention is that the nanofiber gel formation and mineralization reactions occur in a single mixing step and under substantially neutral or physiological pH conditions. These homogeneous nanostructured composite materials are useful for medical applications especially the regeneration of damaged bone in mammals. This invention is directed to the synthesis of peptide-amphiphiles with more than one amphiphilic moment and to supramolecular compositions comprised of such multi-dimensional peptide-amphiphiles. Supramolecular compositions can be formed by self assembly of multi-dimensional peptide-amphiphiles by mixing them with a solution comprising a monovalent cation.

Claims

1. A composition for material formation on self assembled peptide-amphiphiles comprising:

a solution of at least one ionically charged species of peptide-amphiphile and at least one salt providing at least one ion from the material to be formed and having the same signed ionic charge as the peptide-amphiphile.

2. The composition of claim 1 wherein the peptide-amphiphile includes an amino acid selected from the group consisting of serine, phosphorylated serine, aspartic acid, β

-amino acids, and γ

-amino acids.

3. The composition of claim 1 wherein the pH of the solution is adjusted to substantially physiological pH.

4. A method of making materials on self assembled peptide-amphiphiles, the method comprising:

preparing a first solution with at least one ionically charged species of peptide-amphiphile and at least one salt providing at least one ion from the material and having the same signed ionic charge as the peptide-amphiphile;

preparing a second solution with an ion from the material and having opposite signed ionic charge to the peptide-amphiphile of said first solution; and

mixing said first and second solutions to self-assemble said peptide amphiphiles into nanofibers and a nanofiber gel and to form said material substantially on said nanofiber surfaces.

5. The method claim 4 further comprising aging the mixture of said first and second solutions to control the size and rate of growth of material on the self-assembled peptide amphiphile nanofibers.

6. The method of claim 4 further comprising:

adjusting the pH of one of the solutions prior to mixing them together.

7. The method claim 4 wherein said material is used in the treatment of a patient with said material further comprising:

administering to a site in need on the patient an effective amount of at least one ionically charged species of peptide-amphiphile and at least one salt providing at least one ion from the material to be formed and having the same signed ionic charge as the peptide-amphiphile.

8. The method of claim 7 further comprising administering to the site in need on the patient at least one salt having opposite signed charge to the peptide-amphiphile.

9. A composition comprising:

a material nucleated and grown on the surface of nanofibers in a nanofiber gel;

said material grown and oriented on the surfaces of said fibers substantially throughout the nanofiber gel.

10. The composition of claim 9 wherein said nanofibers are formed from self-assembled peptide amphiphiles.

11. The composition of claim 9 wherein said material is chosen from the group consisting of biominerals, magnetic materials, conductive materials, nerves, tissue, and cells.