Compositions comprising nanostructures for cell, tissue and artificial organ growth, and methods for making and using same

Patent metadata

Field	Value
Publication number	US-9844657-B2
Application number	US-201615043382-A
Country	US
Kind code	B2
Filing date	Feb 12, 2016
Priority date	Apr 28, 2005
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

The invention provides articles of manufacture comprising biocompatible nanostructures comprising nanotubes and nanopores for, e.g., organ, tissue and/or cell growth, e.g., for bone, kidney or liver growth, and uses thereof, e.g., for in vitro testing, in vivo implants, including their use in making and using artificial organs, and related therapeutics. The invention provides lock-in nanostructures comprising a plurality of nanopores or nanotubes, wherein the nanopore or nanotube entrance has a smaller diameter or size than the rest (the interior) of the nanopore or nanotube. The invention also provides dual structured biomaterial comprising micro- or macro-pores and nanopores. The invention provides biomaterials having a surface comprising a plurality of enlarged diameter nanopores and/or nanotubes.

First claim

What is claimed is:

1. A biocompatible vertically aligned nanotube array structure on a biocompatible substrate comprising a laterally separated nanotube arrangement wherein
i) the outer diameter of the nanotube is from about 10-1000 nm;
ii) the inside diameter of the nanotube is at least about 20%-50% of the outer diameter, or at least about 15%, of the outer diameter;
iii) the height of the nanotube is from between about 40-800 nm;
iv) the aspect ratio is less than about 10;
v) the vertical alignment angle is within from about 0-45 degrees off the vertical direction; and
vi) the lateral spacing between adjacent nanotubes is from about 2-100 nm.

2. An orthopedic or dental implant comprising the biocompatible vertically aligned nanotube array structure of claim 1 , wherein the surface is modified such that it comprises an adherent titanium oxide nanotube array; and optionally upon implantation into an animal results in accelerated bone formation.

3. A multi-functional implant device comprising the biocompatible vertically aligned nanotube array structure of claim 1 , wherein the vertical pores of the nanotubes contain a reservoir of biologically active agents selected from the group consisting of pharmaceutical compositions, therapeutic drugs, cancer drugs, growth factors, proteins, enzymes, hormones, nucleic acids, antibiotics, antibodies, nanoparticles, and a biologically active material.

4. A method of externally controlling release of a colloidal liquid into a subject comprising:
applying external stimulation by alternating current magnetic field to the multifunctional implant device of claim 3 ,
wherein the magnetic field causes agitation, movement and heat production from the magnetic nanoparticles comprised in the colloidal liquid resulting in its release from the implant device.

5. A dual structured biomaterial comprising:
(a) micro- or macro-pores, wherein the micro or macro pores has an average diameter, or equivalent diameter if the pores are not circular, in the range of between about 0.5-1,000 μm, and the entrances of the micro or macro pores have a smaller diameter or size than the rest, or the interior, of the micro or macro pores; and,
(b) a surface area covered with nanotubes, TiO 2 nanotubes, having an average pore diameter in the range of between about 30-600 nm.

6. A two or a three-dimensional array comprising:
(a) a solid substrate comprising Ti wires, ribbons or rods, or any combination thereof; and
(b) a plurality of vertically aligned, laterally spaced, nanotubes associated with the substrate, wherein each nanotube comprises a nanopore wherein the outer diameter of each nanotube is about 10-1000 nm; or about 30-300 nm; about 60-200 nm and wherein:
(a) the nanopore of each nanotube comprises a diameter of about at least about 20% to 50% of the outer diameter;
(b) the nanopore of each nanotube comprises a diameter of at least about 15% of the outer diameter of the nanotube;
(c) the two or a three-dimensional array of (b), wherein the nanopore of each nanotube comprises a diameter of at least about 20% of the outer diameter of the nanotube;
(d) the two or a three-dimensional array of (c), wherein the nanopore of each nanotube comprises a diameter of at least about 25% of the outer diameter of the nanotube;
(e) the two or a three-dimensional array of (d), wherein the nanopore of each nanotube comprises a diameter of at least about 30% of the outer diameter of the nanotube;
(f) the two or a three-dimensional array of (e), wherein the nanopore of each nanotube comprises a diameter of at least about 35% of the outer diameter of the nanotube;
(g) the two or a three-dimensional array of (f), wherein the nanopore of each nanotube comprises a diameter of at least about 40% of the outer diameter of the nanotube; or
(h) the two or a three-dimensional array of (g), wherein the nanopore of each nanotube comprises a diameter of at least about 45% of the outer diameter of the nanotube.

7. An orthopedic or dental prosthesis comprising a two or a three-dimensional array of claim 6 .

8. The biocompatible vertically aligned nanotube array structure on a biocompatible substrate of claim 1 , wherein:
(a) in step i) the outer diameter of the nanotube is from about 30-300 nm, or from about 60-200 nm;
(b) the biocompatible vertically aligned nanotube array structure of (a), wherein in step i) the outer diameter of the nanotube is from about 60-200 nm;
(c) in step ii) the inside diameter of the nanotube is at least about 25%, 30%, 35%, 40% or 45% of the outer diameter;
(d) the biocompatible vertically aligned nanotube array structure of (c), wherein the inside diameter of the nanotube is at least about 30%;
(e) the biocompatible vertically aligned nanotube array structure of (d), wherein the inside diameter of the nanotube is at least about 35%;
(f) the biocompatible vertically aligned nanotube array structure of (e), wherein the inside diameter of the nanotube is at least about 40%;
(g) the biocompatible vertically aligned nanotube array structure of (f), wherein the inside diameter of the nanotube is at least about 45% of the outer diameter;
(h) in step iii) the height of the nanotube is from between about 100 nm to about 400 nm;
(i) in step iv) the aspect ratio is less than about 10, or less than about 5;
(j) in step v) the vertical alignment angle is within from about 0-30 degrees off the vertical direction; or
(k) in step vi) the lateral spacing between adjacent nanotubes is from about 5 nm to about 30 nm.

9. The biocompatible vertically aligned nanotube array structure on a biocompatible substrate of claim 1 , wherein the structure comprises a vertically aligned titanium oxide nanotube array structure on a titanium or titanium oxide substrate with a laterally separated nanotube arrangement.

10. The biocompatible vertically aligned nanotube array structure on a biocompatible substrate of claim 1 , wherein the biocompatible vertically aligned nanotube array structure comprises a matrix material comprising a biocompatible coating material comprising Ti and Ti oxide, Zr, Hf, Nb, Ta, Mo, W and/or their alloys or oxides of these metals, and/or alloys;
and optionally having a thickness of at least 5 nm;
and optionally having a coating coverage of at least 80% of the nanotube or nanopore surfaces, wherein the matrix material comprises Ti, Zr, Hf, Nb, Ta, Mo, W, and/or their oxides, or alloys of these metals and oxides, and/or Si, Si oxide, Al, Al oxide, carbon, diamond, noble metals, Au, Ag, Pt and/or their alloys, polymer or plastic materials, or composite metals, ceramics and/or polymers.

11. The biocompatible vertically aligned nanotube array structure on a biocompatible substrate of claim 1 , wherein sodium titanate nanostructures are superimposed onto the titanium oxide nanotube array structure; and hydroxyapatite formation is enhanced upon exposure of the nanotube array structure to simulated or living body fluid.

12. The biocompatible vertically aligned nanotube array structure on a biocompatible substrate of claim 1 , wherein the nanotube array structure comprises a plurality of detection elements for the rapid diagnosis or detection of diseased cells, cells involved in an infectious or an epidemic disease or exposed to a chemical or a toxic agent, or cells exposed to a biological warfare agent, or cells that are related to forensic investigations;
and optionally the nanotube array structure and plurality of detection elements are subdivided along an X-Y matrix,
and optionally the detection elements comprise a multiplicity of the nanotubes, wherein the cells are placed and proliferated;
and optionally the diagnosis and detection t

Assignees

• Univ California

Inventors

• Jin Sungho
• Oh Seunghan

Classifications

• A61L2400/12

  Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces · CPC title

• A61K9/0097

  Medicinal compositions released by microdevices, e.g. microelectromechanical systems [MEMS], microdevices comprising chips or microdevices on silicon · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61L2300/43

  Hormones, e.g. dexamethasone · CPC title

• A61L2300/254

  Enzymes, proenzymes · CPC title