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

• US 7,554,021 B2
• Filed: 11/12/2003
• Issued: 06/30/2009
• Est. Priority Date: 11/12/2002
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Hartgerink, Jeffrey D., Beniash, Elia, Stupp, Samuel I.
• Primary Examiner(s): Weber; Jon P
• Assistant Examiner(s): Liu; Samuel W
• Application Number:
  US10/534,097
• Publication Number:
  US 20060149036A1
• Time in Patent Office: 2,057 Days
• Field of Search: 514/2
• US Class Current: 428/113
• 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 method for the mineralization of nanofibers, the method comprising:

preparing a first solution with at least one peptide amphiphile comprising a C₆ or greater hydrocarbon component at its N-terminus and a lyophilic peptide component;

preparing a second solution of a mineral salt; and

mixing said first and second solutions to self-assemble said peptide amphiphiles into nanofibers and a nanofiber gel,

wherein said mineralization occurs from initially dissolved mineral cations and anions along the nanofibers surfaces, wherein said nanofibers are fibrous cylindrical micelles.

2. The method claim 1 further comprising:

aging the mixture of said first and second solutions to control the size and rate of growth of said minerals on the self-assembled peptide amphiphile nanofibers.

3. The method of claim 1 further comprising:

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

4. The method of claim 1, wherein said mineral cations and anions are selected from the group consisting of hydroxyapatite, fluoroapatite, calcium oxalate, calcite, tin hydrogen phosphate, iron oxides, iron hydroxides, iron oxyhydroxyoxides, titanium dioxide, and zinc oxide.

5. The method of claim 1, wherein the peptide-amphiphile has a net negative charge.

6. The method of claim 4, wherein the mineral is hydroxyapatite.