Bioprosthetic heart valve with polyphosphazene

1. A bioprosthetic heart valve comprising a biological tissue and a polyphosphazene represented by formula (I):

wherein

n is 2 to ∞; and

R 1 to R 6 are groups which are each selected independently from alkyl, aminoalkyl, haloalkyl, thioalkyl, thioaryl, alkoxy, haloalkoxy, aryloxy, haloaryloxy, alkylthiolate, arylthiolate, alkylsulphonyl, alkylamino, dialkylamino, heterocycloalkyl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof or heteroaryl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof.

2. The bioprosthetic heart valve of claim 1 , wherein at least one of R 1 to R 6 is an alkoxy group substituted with at least one fluorine atom.

3. The bioprosthetic heart valve of claim 1 , wherein the polyphosphazene is poly[bis(trifluoroethoxy)phosphazene].

4. The bioprosthetic heart valve of claim 1 , wherein the polyphosphazene is coated, diffused, impregnated, grafted, or any combination thereof, into or onto the biological tissue.

5. The bioprosthetic heart valve of claim 1 , wherein the polyphosphazene is coated onto the biological tissue at a thickness of from about 1 nm to about 100 μm.

6. The bioprosthetic heart valve of claim 1 , wherein the polyphosphazene has an average molecular weight of about 10 to about 13 million Daltons.

7. The bioprosthetic heart valve of claim 1 , wherein the biological tissue comprises at least one of a mammalian heart valve, a mammalian pericardium, or a mammalian vascular graft.

8. A method of manufacturing a bioprosthetic heart valve, comprising

providing a biological tissue; and

contacting the biological tissue with a polyphosphazene of formula (I):

 wherein

n is 2 to ∞; and

R 1 to R 6 are groups which are each selected independently from alkyl, aminoalkyl, haloalkyl, thioalkyl, thioaryl, alkoxy, haloalkoxy, aryloxy, haloaryloxy, alkylthiolate, arylthiolate, alkylsulphonyl, alkylamino, dialkylamino, heterocycloalkyl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof, or heteroaryl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof.

9. The method of claim 8 , wherein the polyphosphazene is coated, diffused, impregnated, grafted, or any combination thereof into or onto the biological tissue.

10. The method of claim 8 , wherein at least one of R 1 to R 6 is an alkoxy group substituted with at least one fluorine atom.

11. The method of claim 8 , wherein the polyphosphazene is poly[bis(trifluoroethoxy)phosphazene].

12. The method of claim 8 , wherein the biological tissue comprises at least one of a mammalian heart valve, a mammalian pericardium, or a mammalian vascular graft.

13. The method of claim 8 , further comprising

combining the polyphosphazene, a fixing agent, a surfactant, and a polyphosphazene soluble organic solvent to form a polyphosphazene solution prior to contacting the biological tissue with the polyphosphazene solution.

14. The method of claim 13 , wherein the polyphosphazene is poly[bis(trifluoroethoxy)phosphazene].

15. The method of claim 13 , wherein the fixing agent is selected from formaldehyde, glutaraldehyde, or a combination thereof.

16. The method of claim 13 , wherein the surfactant is selected from a polysorbate, a poloxamer, glycerol, polyethylene imines, chitosans, polyallylamines, polyvinyl pyrrolidone, PVP, DEAE dextran, or a combination thereof.

17. A method of improving the antithrombogenic, biocompatibility, or hemocapatibility properties of a bioprosthetic heart valve, comprising:

contacting the bioprosthetic heart valve with a polyphosphazene of formula (I):

 wherein

n is 2 to ∞; and

R 1 to R 6 are groups which are each selected independently from alkyl, aminoalkyl, haloalkyl, thioalkyl, thioaryl, alkoxy, haloalkoxy, aryloxy, haloaryloxy, alkylthiolate, arylthiolate, alkylsulphonyl, alkylamino, dialkylamino, heterocycloalkyl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof, or heteroaryl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof;

wherein the polyphosphazene is coated, diffused, impregnated, grafted, or any combination thereof, into or onto the bioprosthetic heart valve.

18. The method of claim 17 , wherein the polyphosphazene is coated onto the bioprosthetic heart valve at a thickness of from about 1 nm to about 100 μm.

19. The method of claim 17 , wherein at least one of R 1 to R 6 is an alkoxy group substituted with at least one fluorine atom.

20. The method of claim 17 , wherein the polyphosphazene is a poly[bis(trifluoroethoxy)phosphazene].

21. The method of claim 17 , wherein the polyphosphazene has a molecular weight of about 10 to about 13 million Daltons.

22. The method of claim 17 , further comprising

combining the polyphosphazene, a fixing agent, a surfactant, and a polyphosphazene soluble organic solvent to form a polyphosphazene solution prior to contacting the bioprosthetic heart valve with the polyphosphazene solution;

wherein the polyphosphazene is a poly[bis(trifluoroethoxy)phosphazene];

the fixing agent is selected from formaldehyde, glutaraldehyde, or a combination thereof; and

the surfactant is selected from a polysorbate, a poloxamer, glycerol, or a combination thereof.

23. A bioprosthetic heart valve comprising a mammalian heart valve and a poly-[bis(trifluoroethoxy)phosphazene].

24. A method of making a bioprosthetic heart valve comprising

providing a mammalian heart valve; and

contacting the mammalian heart valve with a poly[bis(trifluoroethoxy)-phosphazene];

wherein the poly[bis(trifluoroethoxy)phosphazene] is coated, diffused, impregnated, grafted, or any combination thereof, into or onto the mammalian heart valve.