Polymer nanofiber scaffolds and uses thereof

Patent metadata

Field	Value
Publication number	US-10576181-B2
Application number	US-201816026228-A
Country	US
Kind code	B2
Filing date	Jul 3, 2018
Priority date	Feb 10, 2014
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

A polymer nanofiber scaffold includes a plurality of melt extruded nanofibers that are chemically modified to append surface functionality to the nanofibers.

First claim

Having described the invention, we claim:

1. A method of forming an agent functionalized polymer nanofiber scaffold, the method comprising:
providing a plurality of melt extruded polymer nanofibers, the nanofibers each having a rectangular cross-section defined in part by an encapsulating polymer material that is separated from the nanofibers,
chemically bonding a plurality of click-reactive functional groups of a specific binding pair to the fibers without degrading polymer chains of the nanofibers, the click-reactive functional groups extending from portions of outer surfaces of the nanofibers; and
appending at least one agent to the nanofibers by reacting an agent conjugated to a complementary click-reactive group of the specific binding pair with the click-reactive functional groups of the nanofibers;
wherein the surface area of the nanofiber is greater than 40.0 cm 2 /mg of fiber.

2. The method of claim 1 , wherein the agent comprises at least one a bioactive agent, diagnostic agent, therapeutic agent, catalyst, charged molecule, peptide, polypeptide, nucleic acid, polynucleotide, small molecule, nanoparticle, antibody, carbohydrate, or vector.

3. The method of claim 1 , the nanofibers are formed by:
coextruding a first polymer material with a second polymer material to form a coextruded polymer film having discrete overlapping layers of polymeric material;
multiplying the overlapping layers to form a multilayered composite film; and
separating the first polymer material from the second polymer material to form the plurality of nanofibers having the rectangular cross-section.

4. The method of claim 3 , wherein separating the polymer materials includes subjecting the multilayered composite film to a high pressure water stream.

5. The method of claim 3 , wherein separating the polymer materials includes subjecting the multilayered composite film to a high pressure air stream.

6. The method of claim 3 , dissolving the second polymer material.

7. The method of claim 1 , wherein concentration of functional click-reactive function groups extending from at least one portion is at least about 0.1 nmol/cm 2.

8. The method of claim 1 , wherein the functional groups are spatially arranged on the nanofibers such that a first portion of the nanofibers has first concentration of functional groups and a second portion of the nanofibers has a second concentration of functional groups different than the concentration of the first portion.

9. The method of claim 1 , wherein the functional groups are spatially arranged on the nanofibers such that different portions of the nanofibers have different concentrations of the functional groups.

10. The method of claim 1 , wherein the functional groups are spatially arranged on the nanofibers in a concentration gradient.

11. The method of claim 1 , wherein the plurality of click-reactive function groups including first click reactive functional groups and second click reactive functional groups different than the first click reactive functional groups.

12. The method of claim 1 , wherein the functional groups are chemically bound to the nanofibers by reacting a click-reactive functional group substituted diarylketone with the polymer chains of the nanofibers.

13. The method of claim 1 , the click-reactive functional groups comprising at least one of an amine, sulfate, thiol, hydroxyl, azide, alkyne, alkene, carboxyl groups, aldehyde groups, sulfone groups, vinylsulfone groups, isocyanate groups, acid anhydride groups, epoxide groups, aziridine groups, episulfide groups, —CO 2 N(COCH 2 ) 2 , —CO 2 N(COCH 2 ) 2 , —CO 2 H, —CHO, —CHOCH 2 , —N═C═O, —SO 2 CH═CH 2 , —N(COCH) 2 , —S—S—(C 5 H 4 N)and groups of the following structures,

wherein R 1 is hydrogen or C 1 to C 4 alkyl.

14. The method of claim 1 , wherein the nanofibers are formed of a polycaprolactone.

15. A method of forming a surface functionalized polymer nanofiber scaffold, the method comprising:
providing a plurality of melt extruded polymer nanofibers, the nanofibers each having a rectangular cross-section defined in part by an encapsulating polymer material that is separated from the nanofibers, and
chemically bonding a plurality of click-reactive functional groups to the fibers without degrading polymer chains of the nanofibers, the click-reactive functional groups extending from portions of outer surfaces of the nanofibers;
wherein the surface area of the nanofiber is greater than 40.0 cm 2 /mg of fiber.

16. The method of claim 15 , the nanofibers are formed by:
coextruding a first polymer material with a second polymer material to form a coextruded polymer film having discrete overlapping layers of polymeric material;
multiplying the overlapping layers to form a multilayered composite film; and
separating the first polymer material from the second polymer material to form the plurality of nanofibers having the rectangular cross-section.

17. The method of claim 16 , wherein separating the polymer materials includes subjecting the multilayered composite film to a high pressure water stream.

18. The method of claim 16 , wherein separating the polymer materials includes subjecting the multilayered composite film to a high pressure air stream.

19. The method of claim 16 , further comprising dissolving the second polymer material.

20. The method of claim 15 , wherein concentration of functional click-reactive function groups extending from at least one portion is at least about 0.1 nmol/cm 2 .

21. The method of claim 15 , wherein the functional groups are spatially arranged on the nanofibers such that a first portion of the nanofibers has first concentration of functional groups and a second portion of the nanofibers has a second concentration of functional groups different than the concentration of the first portion.

22. The method of claim 15 , wherein the functional groups are spatially arranged on the nanofibers such that different portions of the nanofibers have different concentrations of the functional groups.

23. The method of claim 15 , wherein the functional groups are spatially arranged on the nanofibers in a concentration gradient.

24. The method of claim 15 , wherein the plurality of click-reactive function groups including first click reactive functional groups and second click reactive functional groups different than the first click reactive functional groups.

25. The method of claim 15 , wherein the functional groups are chemically bound to the nanofibers by reacting a click-reactive functional group substituted diarylketone with the polymer chains of the nanofibers.

26. The method of claim 15 , the click-reactive functional groups comprising at least one of an amine, sulfate, thiol, hydroxyl, azide, alkyne, alkene, carboxyl groups, aldehyde groups, sulfone groups, vinylsulfone groups, isocyanate groups, acid anhydride groups, epoxide groups, aziridine groups, episulfide groups, —CO 2 N(COCH 2 ) 2 , —CO 2 N(COCH 2 ) 2 , —CO 2 H, —CHO, —CHOCH 2 , —N═C═O, —SO 2 CH═CH 2 , —N(COCH) 2 , —S—S—(C 5 H 4 N) and groups of the following structures,

wherein R 1 is hydrogen or C 1 to C 4 alkyl.

27. The method of claim 15 , wherein the nanofibers are

Assignees

• Univ Case Western Reserve

Inventors

• Pokorski Jonathan K
• Baer Eric
• Kim Sieun
• Wang Jia

Classifications

• A61L15/26 Primary

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof {(A61L15/225 takes precedence)} · CPC title

• A61L15/44

  Medicaments · CPC title

• A61L27/60 Primary

  Materials for use in artificial skin · CPC title

• A61L2400/12

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

• A61F2/02

  Prostheses implantable into the body · CPC title