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

Patent ·
OSTI ID:988400

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.

Research Organization:
Northwestern University (Evanston, IL)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG02-00ER45810
Assignee:
Northwestern University (Evanston, IL)
Patent Number(s):
7,554,021
Application Number:
10/534,097
OSTI ID:
988400
Country of Publication:
United States
Language:
English

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Graded Histological and Locomotor Outcomes after Spinal Cord Contusion Using the NYU Weight-Drop Device versus Transection journal June 1996
Microcontact Printing: A Versatile Technique for the Study of Synaptogenic Molecules journal May 2002
Two-Dimensional Arrays of Self-Assembled Gold and Sulfur-Containing Fullerene Nanoparticles journal April 2002
Inhibition of Axon Growth by Oligodendrocyte Precursor Cells journal May 2002
Random Laser Action in Semiconductor Powder journal March 1999
Novel approach to fabricate porous sponges of poly(d,l-lactic-co-glycolic acid) without the use of organic solvents journal July 1996
Structure-activity study of a laminin α1 chain active peptide segment Ile-Lys-Val-Ala-Val (IKVAV) journal May 1995
Viability, adhesion, and bone phenotype of osteoblast-like cells on polyelectrolyte multilayer films: Viability, Adhesion, and Bone Phenotype journal March 2002
On the Structure and Stability of Self-Assembled Zwitterionic Peptide Amphiphiles:  A Theoretical Study journal March 2004
Approaching Exponential Growth with a Self-Replicating Peptide journal June 2002
Structural transitions involved in a novel amyloid-like ?-sheet assemblage of tripeptide derivatives journal October 2003
Flow oriented linear dichroism to probe protein orientation in membrane environments journal January 2002
Self-complementary oligopeptide matrices support mammalian cell attachment journal December 1995
Thermotropic mesophases of ionic amphiphiles: II. Ionic amphiphiles in aqueous media journal November 1994
Biomaterials in Drug Delivery and Tissue Engineering:  One Laboratory's Experience journal February 2000
Effect of chirality on the formation of tubules from glycolipidic amphiphiles journal March 1996
Polysaccharide strong and weak gels journal August 1993
Self-Assembly Combining Two Bioactive Peptide-Amphiphile Molecules into Nanofibers by Electrostatic Attraction journal June 2003
Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix journal October 2000
A method to attach lectins to the surface of spermine alginate microcapsules based on the avidin biotin interaction journal January 1996
Hydroxy- and fluorapatite films on Ti alloy substrates: Sol-gel preparation and characterization journal July 2001
Molecular modeling of protein-glycosaminoglycan interactions. journal January 1989
Sustained release of basic fibroblast growth factor and angiogenesis in a novel covalently crosslinked gel of heparin and alginate journal January 2001
Alginate hydrogels as synthetic extracellular matrix materials journal January 1999
Nano-fibrous scaffolds for tissue engineering journal December 2004
A Transmission Electron Microscope Study Using Vitrified Ice Sections of Predentin: Structural Changes in the Dentin Collagenous Matrix prior to Mineralization journal December 2000
A general method for preparation of peptides biotinylated at the carboxy terminus journal April 1992
Modulation of crystal formation by bone phosphoproteins: role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein journal August 1994
Preparation of the very acid-sensitive Fmoc-Lys(Mtt)-OH Application in the synthesis of side-chain to side-chain cyclic peptides and oligolysine cores suitable for the solid-phase assembly of MAPs and TASPs journal May 1995
The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro journal July 2004
Effect of proteoglycans on in vitro hydroxyapatite formation journal December 1979
Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors journal January 1990
Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers journal February 2004
Conversion of Supramolecular Clusters to Macromolecular Objects journal January 1999
Regional Specification of Neurosphere Cultures Derived from Subregions of the Embryonic Telencephalon journal December 2002
Semiconductor Clusters, Nanocrystals, and Quantum Dots journal February 1996
Neural Tissue Engineering: Strategies for Repair and Regeneration journal August 2003
Spectroscopic investigation on gel-forming ?-sheet assemblage of peptide derivatives journal October 2003
Transplants of Fibroblasts Genetically Modified to Express BDNF Promote Regeneration of Adult Rat Rubrospinal Axons and Recovery of Forelimb Function journal June 1999
Kinetics of the Micelle-to-Vesicle Transition: Aqueous Lecithin-Bile Salt Mixtures journal September 2003
Solid-phase synthesis of C-terminal modified peptides journal January 2003
Mechanism for the Enhanced Diffusion of Charged Oxygen Ions in SiO 2 journal February 2001
Alginate based new materials journal August 1997
Epitope Identification and Discovery Using Phage Display Libraries: Applications in Vaccine Development and Diagnostics journal January 2004
Dicarboxylic Oligopeptide Bolaamphiphiles:  Proton-Triggered Self-Assembly of Microtubes with Loose Solid Surfaces journal September 1998
The Deposition of Calcium Phosphates within Polyelectrolyte Multilayer Films journal May 2003
Selective Adhesion of Endothelial Cells to Artificial Membranes with a Synthetic RGD-Lipopeptide journal March 2001
Functional Arteries Grown in Vitro journal April 1999
Enhanced Oligonucleotide Binding to Self-Assembled Nanofibers journal May 2005
Highly Porous Polymer Matrices as a Three-Dimensional Culture System for Hepatocytes journal September 1997
Hydroxyapatite-Coated Titanium for Orthopedic Implant Applications journal January 1988
Cross-Linking Exogenous Bifunctional Peptides into Fibrin Gels with Factor XIIIa journal January 1999
Ile-Lys-Val-Ala-Val (IKVAV)-containing laminin α1 chain peptides form amyloid-like fibrils journal September 2002