Method of forming a medical device on biological tissue

• US 8,512,728 B2
• Filed: 02/19/2010
• Issued: 08/20/2013
• Est. Priority Date: 02/21/2009
• Status: Active Grant

• Current Assignee: Sofradim Production
• Original Assignee: Sofradim Production
• Inventors: Gravagna, Philippe, Ladet, Sebastien
• Primary Examiner(s): Naff, David M
• Application Number:
  US12/708,798
• Publication Number:
  US 20100217287A1
• Time in Patent Office: 1,278 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• 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

Abstract

A method for in situ formation of a medical device on biological tissue includes attaching a plurality of reactive members of a primary specific binding pair to a surface of the biological tissue, and providing a plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, wherein upon contact of the reactive members on the surface of the biological tissue with the complimentary reactive members on the fibers, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the fibers to the tissue. The fibers can incorporate functionalities which may cause them to bind to one another.

Claims

1. A method of forming a medical device on biological tissue comprising:

attaching a plurality of reactive members of a primary specific binding pair to a surface of the biological tissue;

providing a plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, and a plurality of reactive members and complementary reactive members of an orthogonal specific binding pair, wherein upon contact of the reactive members of the primary specific binding pair on the surface of the biological tissue with the complimentary reactive members of the primary specific binding pair on the fibers, covalent bonds are formed via click chemistry between the reactive members and the complementary reactive members of the primary specific binding pair, adhering the fibers to the biological tissue, and, wherein upon contact of the reactive members of the orthogonal specific binding pair on the fibers with the complimentary reactive members of the orthogonal specific binding pair on the fibers, covalent bonds are formed via click chemistry between the reactive members and the complementary reactive members of the orthogonal specific binding pair, adhering the fibers to each other.

2. The method of forming a medical device on biological tissue according to claim 1 wherein the plurality of fibers further comprise reactive members and the complementary reactive members of a second orthogonal specific binding pair capable of causing the plurality of fibers to bind to each other.

3. The method of forming a medical device on biological tissue according to claim 1 wherein the reactive members and the complementary reactive members of the primary specific binding pair bind to one another to form covalent bonds via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

4. The method of forming a medical device on biological tissue according to claim 3 wherein the reactive members and the complementary reactive members of the primary specific binding pair are alkynes and azides.

5. The method of forming a medical device on biological tissue according to claim 2 wherein the plurality of fibers comprises a first group of the plurality of fibers with a plurality of reactive members of the second orthogonal specific binding pair and a second group of the plurality of fibers with a plurality of complementary reactive members of the second orthogonal specific binding pair, wherein upon contact of the reactive members of the second orthogonal specific binding pair with the complimentary reactive members of the second orthogonal specific binding pair, covalent bonds are formed between the reactive members and the complementary reactive members of the second orthogonal specific binding pair, adhering the first and second group of fibers to each other.

6. The method of forming a medical device on biological tissue according to claim 5 wherein the reactive members and the complementary reactive members of the second orthogonal specific binding pair bind to one another to form covalent bonds via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

7. The method of forming a medical device on biological tissue according to claim 6 wherein the reactive members and the complementary reactive members of the second orthogonal specific binding pair bind to one another to form covalent bonds via a reaction which is different than the reaction of the orthogonal specific binding pair.

8. The method of forming a medical device on biological tissue according to claim 6 wherein the reactive members and the complementary reactive members of the second orthogonal specific binding pair bind to one another to form covalent bonds via a reaction which is different than the reaction of the primary specific binding pair.

9. The method of forming a medical device on biological tissue according to claim 1 wherein reactive members of the primary specific binding pair are attached to the tissue to form covalent bonds via attachment to a moiety selected from the group consisting of an N-terminus of a protein of the tissue, a C-terminus of a protein of the tissue, an oligosaccharide, a lipid, a glycan and an oligonucleotide.

10. The method of forming a medical device on biological tissue according to claim 1 wherein reactive members of the primary specific binding pair are attached to the biological tissue by applying a mixture or an aerosol containing the reactive members to the biological tissue, the reactive members being conjugated to a linker adapted to link the reactive members to the biological tissue.

11. The method of forming a medical device on biological tissue according to claim 10 wherein the reactive members of the primary specific binding pair are attached to the biological tissue via an RGD linker.

12. The method of forming a medical device on biological tissue according to claim 10 wherein the reactive members of the primary specific binding pair are attached to the biological tissue via a ligand-receptor linkage.

13. The method of forming a medical device on biological tissue according to claim 12 wherein the reactive members of the primary specific binding pair are conjugated to a linker selected from the group consisting of antibody, Fab, F(ab′

)₂, Fv, single chain antibody (SCA) and single complementary-determining region (CDR).

14. The method of forming a medical device on biological tissue according to claim 10 wherein the linker is degraded by hydrolysis or enzymatic action.

15. The method of forming a medical device on biological tissue according to claim 12 wherein the ligand binds to a receptor selected from the group consisting of peptides, oligosaccharides, oligonucleotides, glycans and lipids.

16. The method of forming a medical device on biological tissue according to claim 1 wherein the fibers are nanofibers.

17. The method of forming a medical device on biological tissue according to claim 1 wherein the reactive members of the primary specific binding pair are applied to the surface of the biological tissue in a predetermined geometric pattern.

18. The method of forming a medical device on biological tissue according to claim 17 wherein the predetermined geometric pattern defines a mesh.

19. The method of forming a medical device on biological tissue according to claim 1 wherein the plurality of fibers are made of a polymer selected from the group consisting of polycarbonates, polyolefins, polymethacrylates, polystyrenes, polyamides, polyurethanes, polyethylene terephthalate, poly (lactic acid), poly (glycolic acid), poly (hydroxbutyrate), poly (phosphazine), polyesters, polyethylene glycol, polyethylene oxides, polyacrylamides, fluoropolymers, vinyl polymers, silk, collagen, alginate, chitin, chitosan, hyaluronic acid, chondroiten sulfate, polyhydroxyethylmethylacrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polypropylene, glycerols, poly(amino acids), copoly (ether-esters), polyalkylene oxalates, polyamides, poly (iminocarbonates), polyoxaesters, polyorthoesters, polyphosphazenes, polypeptides and copolymers, block copolymers, homopolymers, blends and combinations thereof.

20. The method of forming a medical device on biological tissue according to claim 1 wherein the fibers adhere to the biological tissue in the form of a medical device selected from the group consisting of a mesh, patch, adhesion barrier and hemostat.

21. A method of forming a medical device on biological tissue comprising:

attaching a plurality of reactive members of a primary specific binding pair to a surface of the biological tissue;

providing a first plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, and a plurality of reactive members of an orthogonal specific binding pair, wherein upon contact of the reactive members of the primary specific binding pair on the surface of the biological tissue with the complimentary reactive members of the primary specific binding pair on the first plurality of fibers, covalent bonds are formed via click chemistry between the reactive members and the complementary reactive members of the primary specific binding pair, adhering the first plurality of fibers to the biological tissue; and

,

providing a second plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, and a plurality of complementary reactive members of the orthogonal specific binding pair, wherein upon contact of the reactive members of the primary specific binding pair on the surface of the biological tissue with the complimentary reactive members of the primary specific binding pair on the second plurality of fibers, covalent bonds are formed via click chemistry between the reactive members and the complementary reactive members of the primary specific binding pair, adhering the second plurality of fibers to the biological tissue, and, wherein upon contact of the reactive members of the orthogonal specific binding pair on the first plurality of fibers with the complimentary reactive members of the orthogonal specific binding pair on the second plurality of the fibers, covalent bonds are formed via click chemistry between the reactive members and the complementary reactive members of the orthogonal specific binding pair, adhering the first and second plurality of fibers to each other.

22. The method of forming a medical device on biological tissue according to claim 21 wherein the reactive members and the complementary reactive members of the orthogonal specific binding pair bind to one another to form covalent bonds via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

23. The method of forming a medical device on biological tissue according to claim 22 wherein the reactive members and the complementary reactive members of the orthogonal specific binding pair bind to one another to form covalent bonds via a reaction which is different than the reaction of the primary specific binding pair.

24. The method of forming a medical device on biological tissue according to claim 21 wherein the reactive members and the complementary reactive members of the primary specific binding pair bind to one another to form covalent bonds via a reaction catalyzed by copper to activate an alkyne and an azide for [3+2] cycloaddition.

25. The method of forming a medical device on biological tissue according to claim 21 wherein the reactive members and the complementary reactive members of the primary specific binding pair bind to one another to form covalent bonds via a reaction comprising a cyclooctyne reagent and an azide for [3+2] cycloaddition.

26. A method of forming a medical device on biological tissue comprising:

attaching a plurality of reactive members of a primary specific binding pair and a plurality of reactive members of a secondary specific binding pair to the surface of the biological tissue;

providing a first plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, wherein upon contact of the reactive members of the primary specific binding pair on the surface of the biological tissue with the complimentary reactive members of the primary specific binding pair on the first plurality of fibers, covalent bonds are formed via click chemistry between the reactive members and the complementary reactive members of the primary specific binding pair, adhering the first plurality of fibers to the biological tissue; and

providing a second plurality of fibers having attached thereto a plurality of complementary reactive members of the secondary specific binding pair, wherein upon contact of the reactive members of the secondary specific binding pair on the surface of the biological tissue with the complimentary reactive members of the secondary specific binding pair on the second plurality of fibers, covalent bonds are formed via click chemistry between the reactive members and the complementary reactive members of the secondary specific binding pair, adhering the second plurality of fibers to the biological tissue.

27. The method of forming a medical device on biological tissue according to claim 26 wherein the first plurality of fibers further comprises a plurality of reactive members of an orthogonal specific binding pair, and the second plurality of fibers further comprises a plurality of complementary reactive members of the orthogonal specific binding pair, wherein upon contact of the reactive members of the orthogonal specific binding pair on the first plurality of fibers with the complimentary reactive members of the orthogonal specific binding pair on the second plurality of the fibers, covalent bonds are formed via click chemistry between the reactive members and the complementary reactive members of the orthogonal specific binding pair, adhering the first and second plurality of fibers to each other.

28. The method of forming a medical device on biological tissue according to claim 26 wherein the first plurality of fibers are applied to the surface of the biological tissue in a first geometric pattern and the second plurality of fibers are applied to the surface of the biological tissue in a second geometric pattern.

29. The method of forming a medical device on biological tissue according to claim 28 wherein the first geometric pattern and the second geometric pattern intersect.

30. The method of forming a medical device on biological tissue according to claim 26 further comprising:

attaching a plurality reactive members of a tertiary specific binding pair to the surface of the biological tissue; and

providing a third plurality of fibers having attached thereto a plurality of complementary reactive members of the tertiary specific binding pair, wherein upon contact of the reactive members of the tertiary specific binding pair on the surface of the biological tissue with the complimentary reactive members of the tertiary specific binding pair on the third plurality of fibers, covalent bonds are formed between the reactive members and the complementary reactive members of the tertiary specific binding pair, adhering the third plurality of fibers to the biological tissue.

31. The method of forming a medical device on biological tissue according to claim 30 wherein the third plurality of fibers intertwines with the first plurality of fibers and the second plurality of fibers.

32. The method of forming a medical device on biological tissue according to claim 30 wherein the first plurality of fibers are applied to the surface of the biological tissue in a first geometric pattern and the third plurality of fibers are applied to the surface of the biological tissue in a different geometric pattern.

33. The method of forming a medical device on biological tissue according to claim 32 wherein the first geometric pattern and the different geometric pattern intersect.