Glycosaminoglycan and synthetic polymer materials for blood-contacting applications
View Patent ↗Provided herein is a composite, comprising: a polymer host selected from the group consisting of low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), polypropylene (PP), polyurethane, polycaprolactone (PCL), polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), and polyoxymethylene (POM); and a guest molecule comprising hyaluronic acid; wherein the guest molecule is disposed within the polymer host, and wherein the guest molecule is covalently bonded to at least one other guest molecule. Also provided herein are methods for forming the composite, and blood-contracting devices made from the composite, such as heart valves and vascular grafts.
1. A method for preparing a composite, the method comprising:
a. providing a polymer host selected from a group consisting of low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), polypropylene (PP), polyurethane, polycaprolactone (PCL), polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), polyoxymethylene (POM), and combinations thereof, disposed with at least one protected guest molecules, the protected guest molecules comprising hyaluronic acid with a protecting group; and
b. exposing the polymer host disposed with at least one protected guest molecule to a vaporized cross-linking agent, whereby the protected guest molecule covalently binds to at least one other guest molecule, such that the cross-linked guest molecules interpenetrate the polymer host molecule at a nanometer scale.
2. The method of claim 1 , further comprising deprotecting the at least one protected guest molecule to remove the protecting group.
3. The method of claim 1 , wherein the polymer host is LLPDE.
4. The method of claim 1 , wherein the polymer host is PET.
5. The method of claim 4 , wherein the PET is a fabric.
6. The method of claim 1 , wherein the polymer host is expanded (ePTFE).
7. The method of claim 1 , wherein the polymer host has a thickness from about 5 μm to about 2 mm.
8. The method of claim 1 , wherein the polymer host has a thickness from about 5 μm to about 1500 μm.
9. The method of claim 1 , wherein the cross-linking agent is selected from a group consisting of an aliphatic diisocyanate, an aromatic diisocyanate, a polyisocyanate, a dialdehyde, an aldehyde, a dihydrazide, a polyaziridine, or a divinyl compound.
10. The method of claim 9 , wherein the cross-linking agent is selected from a group consisting of hexamethylenediisocyanate, m-tetramethylene diisocyanate, diphenylmethane diisocyanate, toluene 2,4-diisocyanate, toluene 2,6-diisocyanate, 1,4-phenylene diisocyanate, glutaraldehyde, formaldehyde, divinyl sulfone, adipic acid dihydrazide, polyaziridine, or combinations thereof.
11. The method of claim 9 , wherein the cross-linking agent is toluene 2,4-diisocyanate, toluene 2,6-diisocyanate, or combinations thereof.
12. The method of claim 1 , wherein of claim 1 , wherein the vaporized-crosslinking agent is neat or a solution.
13. The method of claim 12 , wherein the concentration of the cross-linking agent in the solvent ranges from 0.1% to 50% by volume.
14. The method of claim 12 , wherein the solvent is selected from a group consisting of a non-polar solvent, a polar aprotic solvent, or combinations thereof.
15. The method of claim 14 , wherein the solvent is selected from a group consisting of supercritical dimethyl sulfoxide, acetone, carbon dioxide, toluene, decalin, trichlorobenzene, xylenes, tetrahydrofuran, heptane, hexane, acetonitrile, methylene chloride, chloroform, dichloroethane, dimethyl formamide, N-methyl pyrrolidone, N, N-dimethylacetamide, or combinations thereof.
16. The method of claim 1 , wherein exposing the polymer host disposed with at least one protected guest molecule to a vaporized cross-linking agent occurs at a temperature from about 0° C. to 250° C.
17. The method of claim 1 , wherein exposing the polymer host disposed with at least one protected guest molecule to a vaporized cross-linking agent occurs from about 10 minutes to about 180 minutes.
18. The method of claim 1 , wherein the composite is dried under atmospheric pressure or under vacuum.
19. The method of claim 1 , wherein the average molecular weight of the guest molecule is from 0.5 kDa to about 3,000 kDa.
20. The method of claim 19 , wherein the average molecular weight of the guest molecule is from 0.75 kDa to about 1,000 kDa.
21. The method of claim 1 , wherein the percentage of the cross-linked guest molecule within the composite is from about 0.1% to about 15% by weight.
22. The method of claim 1 , wherein the aqueous static and receding contact angles of the composite is from 10 to 90.