Biodegradable nanocomposites with enhanced mechanical properties for soft tissue engineering

• US 9,750,845 B2
• Filed: 11/18/2013
• Issued: 09/05/2017
• Est. Priority Date: 09/28/2005
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Ameer, Guillermo, Webb, Antonio R.
• Primary Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US14/083,071
• Publication Number:
  US 20140135407A1
• Time in Patent Office: 1,387 Days
• Field of Search: None
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 47/30 Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention is directed to a novel poly(diol citrates)-based nanocomposite materials created using completely biodegradable and biocompatible polymers that may be used in tissue engineering. More specifically, the specification describes methods and compositions for making and using nanocomposites comprised of citric acid copolymers and polymers including but not limited to poly(L-lactic acid) (PLLA) and poly(lactic-co-glycolic acid) (PLGA).

Claims

1. A method, comprising:

(a) combining a poly(diol citrate) pre-polymer solution with a nanostructured poly(L-lactic acid) to form a mixture;

(b) polymerizing the mixture to form a nanocomposite comprising polymerized poly(diol citrate) and nanostructured poly(L-lactic acid);

(c) hydrolyzing the poly(L-lactic acid) during the polymerization step to form free carboxyl groups on the surface of the nanostructured poly(L-lactic acid); and

(d) forming covalent bonds between the free carboxyl groups on the surface of the hydrolyzed poly(L-lactic acid) and the polymerized poly(diol citrate).

2. The method of claim 1 wherein said poly(diol citrate) comprises monomers of citric acid and a linear diol comprising between 2 and 20 carbons.

3. The method of claim 2, wherein said poly(diol citrate) comprises citric acid and 1,8-octanediol monomers.

4. The method of claim 2, wherein said poly(diol citrate) comprises citric acid and 1,10-decanediol monomers.

5. The method of claim 1, further comprising a step of removing solvent and/or water before the polymerizing step.

6. The method of claim 1 wherein said poly(diol citrate) comprises two different linear diol monomers.

7. The method of claim 1, wherein said nanostructured poly(L-lactic acid) is fabricated into nanofibers.

8. The method of claim 1, wherein said nanostructured poly(L-lactic acid) is formulated into nanoparticles.

9. The method of claim 1, further comprising forming mechanically interlocked chains between the polymerized poly(diol citrate) and nanostructured poly(L-lactic acid).

10. The method of claim 1, wherein the nanostructured poly(L-lactic acid) has nanopores and wherein the combining step further comprises impregnating the nanopores with the poly(diol citrate) pre-polymer solution.

11. The method of claim 10, wherein the nanopores are completely filled with the poly(diol citrate) pre-polymer solution.

12. The method of claim 1, wherein said poly(diol citrate) comprises two different linear diol monomers, and wherein the method further comprises controlling the Young'"'"'s modulus of the formed nanocomposite by varying the ratio of the two different linear diol monomer.

13. A nanocomposite produced by the method of claim 1.

14. A substrate for use in tissue engineering comprising the nanocomposite of claim 13 formulated into a cell culture substrate.

15. The substrate of claim 14, wherein said substrate further comprises a surface modification.

16. A drug delivery device comprising a drug interspersed in the nanocomposite of claim 13.