D, L-cyclic peptide nanotube reinforcing agents
The disclosed subject matter can provide a nanotube-reinforced polymer composite material comprising a plurality of nanotubes, each nanotube being formed of a plurality of cyclic peptide molecules, disposed within a polymer matrix, such as a biodegradable polymer matrix. A cyclic polymer, such as a cyclic 8-mer, composed of amino acid residues of alternating absolute configurations (D/L, R/S), can self-assemble into nanotubes useful for preparation of the composite polymer material of the invention. For example, the cyclic peptide (QL)4, wherein the glutamine and leucine residues are of opposite absolute configuration, self-assembles into nanotubes, which when formed into a reinforced polymer composite including poly(caprolactone), provides a biocompatible material of greater tensile strength and Young's modulus compared to the poly(caprolactone) material alone. The nanotubes can be prepared by a vapor equilibration technique or by a solvent-nonsolvent precipitation technique. The materials of the invention can be used for implants, stents and the like as well as for synthetic ligaments, tendons, cartilage, and bone for use in the living tissue of a patient in need thereof. For example, a spinal fusion cage comprising a PDLLA polymer matrix with a plurality of nanotubes of the invention can exhibit enhanced stiffness.
1. A nanotube-reinforced polymer composite, comprising a plurality of nanotubes within a polymer matrix,
wherein each nanotube comprises a self-assembling, non-covalently bonded plurality of D,L cyclic peptide molecules,
wherein each D,L cyclic peptide molecule is a cyclic oligomer of about 6-12 α-amino acid residues, wherein each amino acid residue bears an α-hydrogen atom and a non-hydrogen α-substituent,
wherein the amino acid residues of each cyclic peptide molecule have alternating absolute configurations,
and wherein the amino acid residues of each D,L cyclic peptide molecule comprise a first type of amino acid of a first absolute configuration, and a second type of amino acid of an opposite absolute configuration.
2. The composite of claim 1 , wherein the nanotubes are aligned with each other within the polymer matrix.
3. The composite of claim 1 , wherein the nanotubes are substantially randomly disposed within the polymer matrix.
4. The composite of claim 1 , wherein the polymer matrix comprises one or more biocompatible polymers.
5. The composite of claim 1 , wherein the polymer matrix comprises a polymer selected from the group consisting of a poly(caprolactone), a poly(caprolactone)/gelatin blend, a poly(lactide), a poly(glycolide), a poly(lactide-glycolide), a poly-D,L-lactic acid chitosan, hyaluronic acid, cellulose, alginate, silk, or any combination thereof.
6. The composite of claim 1 , wherein the first type of amino acid is glutamine and the second type of amino acid is leucine, wherein the glutamine and the leucine are of opposite absolute configuration; or wherein the first type of amino acid is glutamate and the second type of amino acid is alanine, wherein the glutamate and the alanine are of opposite absolute configuration.
7. The composite of claim 1 , further comprising a third type of amino acid, wherein the third type of amino acid substitutes in the cyclic peptide for an amino acid residue of the same absolute configuration.
8. The composite of claim 1 , wherein the D,L cyclic peptide molecule comprises amino acids bearing functionalized sidechains for subsequent interaction with a derivatizing material.
9. The composite of claim 8 , wherein the functionalized sidechains are adapted for interaction with a target body tissue substrate for tissue repair.
10. The composite of claim 9 , wherein the target body tissue substrate comprises bone, tendon, ligament, or cartilage.
11. A synthetic biostructure comprising the composite of claim 1 .
12. The synthetic biostructure of claim 11 , wherein the synthetic biostructure is a fiber, a stent, a suture, a wound dressing, a spinal fusion cage, a bone screw or plate, or a synthetic ligament, tendon, cartilage, or bone material.
13. The synthetic biostructure of claim 12 , wherein the synthetic biostructure is a fiber, and wherein the fiber is prepared by electrospinning of the polymer comprising the plurality of nanotubes therein.
14. The synthetic biostructure of claim 12 , wherein the synthetic biostructure is a fiber, and wherein the plurality of nanotubes are aligned parallel to the length of the fiber.
15. The synthetic biostructure of claim 11 , comprising a mat comprising a plurality of aligned or non-aligned fibers.
16. The synthetic biostructure of claim 11 , comprising an injection-molded polymer comprising the plurality of nanotubes therein.
17. The synthetic biostructure of claim 16 , injection molded into a spinal fusion cage or a bone screw or plate.
18. A method of preparing the composite of claim 1 , comprising, first preparing self-assembled nanotubes from D,L cyclic peptide molecules, then, incorporating the nanotubes into the polymer matrix.
19. The method of claim 18 , wherein the nanotubes are prepared by precipitation from a solvent by a non-solvent.
20. The method of claim 19 , wherein the solvent is trifluoracetic acid and the non-solvent is water, or wherein the polymer matrix is poly(caprolactone), a poly(caprolactone)-gelatin blend, poly(lactide-glycolide) or poly-D,L-lactic acid, or any combination thereof, or both.
21. A method of repairing a damaged ligament, tendon, cartilage, or bone, comprising use of a composite of claim 1 , or a synthetic biostructure of claim 11 , to fill, reinforce, or to connect the ligament, tendon, cartilage or bone to a substrate.
22. A method of repairing a damaged spinal column, comprising disposing the spinal fusion cage of claim 12 around a section of spinal column of a patient in need thereof.
23. A nanotube-reinforced polymer composite, comprising a plurality of nanotubes within a polymer matrix,
wherein each nanotube comprises a self-assembling plurality of D,L cyclic peptide molecules bonded together only by inter-peptide hydrogen bonding,
wherein each D,L cyclic peptide molecule is a cyclic oligomer of about 6-12 α-amino acid residues each bearing an α-hydrogen atom and a non-hydrogen α-substituent,
wherein the amino acid residues of each cyclic peptide molecule have alternating absolute configurations,
and wherein the amino acid residues of each cyclic peptide molecule include a first type of amino acid of a first absolute configuration, and a second type of amino acid of an opposite absolute configuration.