Glycosaminoglycan and Synthetic Polymer Material for Blood-Contacting Applications

• US 20150196688A1
• Filed: 03/11/2013
• Published: 07/16/2015
• Est. Priority Date: 03/12/2012
• Status: Active Grant

• Current Assignee: Colorado State University Research Foundation
• Original Assignee: Colorado State University Research Foundation
• Inventors: James, Susan P., Dean, Harold IV, Dasi, Lakshmi Prasad, Popat, Ketul C., Forleo, Marcio H., Lewis, Nicole R., Prawel, David Alois
• Granted Patent: US 10,071,186 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61L 17/10 containing macromolecular materials
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/62 Encapsulated active agents, e.g. emulsified droplets
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• 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 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/126 having a macromolecular matrix
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 31/129 containing macromolecular fillers
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

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), and 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.

Claims

1. 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.

7. The composite of claim 1, wherein the polymer host is a film with a thickness of 25 μ

m to 100 μ

m.

8. The composite of claim 7, wherein the film has a thickness of 50 μ

m.

11. The composite of claim 1, wherein the percentage of cross-linked guest molecules within the composite is 0.2% to 3.5%.

12. The composite of claim 1, wherein the concentration of guest molecule in the composite is greater at the surface of the polymer host than at the core of the polymer host.

15. The composite of claim 1, wherein the aqueous contact angle at the surface of the composite is 10°

to 90°

.

16. The composite of claim 15, wherein the aqueous contact angle at the surface of the composite is 40°

to 80°

.

17. The composite of claim 1, wherein the average molecular weight of the guest molecule is 0.75 kDa to 1,000 kDa.

18. The composite of claim 17, wherein the average molecular weight is 1 kDa to 10 kDa.

2-6. -6. (canceled)

9. (canceled)

10. (canceled)

13. (canceled)

14. (canceled)

19-52. -52. (canceled)

53. A blood-contacting device formed from 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.

55. The device of claim 53, wherein the device is a heart valve, comprising a flow control member selected from the group consisting of a leaflet, a tilting disk, and a ball-in-cage mechanism.

56. The device of claim 53, wherein the composite, upon contact with blood, substantially reduces thrombogenesis or substantially improves endothelialization compared to the polymer host without a guest molecule disposed therein.

72. The device of claim 55, wherein the flow control member is

a leaflet formed from the composite comprising:

the polymer host selected from the group consisting of low-density polyethylene (LDPE) film, linear low-density polyethylene (LLDPE) film, and polyethylene terephthalate (PET) fabric.

73. The device of claim 72, further comprising a suture ring or sewing cuff made from a second composite, comprising:

a second polymer host comprising PET fabric, and

a second guest molecule comprising hyaluronic acid;

wherein the second guest molecule is disposed within the second polymer host, and wherein the second guest molecule is covalently bonded to at least one other second guest molecule.

85. The device of claim 53, wherein the device is a small-diameter vascular graft formed from the composite comprising:

the polymer host comprising expanded polytetrafluoroethylene (ePTFE).

94. The device of claim 55, wherein the flow control member is

a tilting disk formed from a first composite comprising:

a first polymer host comprising ultra-high molecular weight polyethylene (UHMWPE), and

a first guest molecule comprising hyaluronic acid;

wherein the first guest molecule is disposed within the first polymer host, and

wherein the first guest molecule is covalently bonded to at least one other first guest molecule; and

a suture ring made from the composite, comprising;

the polymer host comprising PET fabric.

96. The device of claim 53, wherein the device is a suture ring or sewing cuff made from the composite, and the polymer host comprises PET fabric.

54. (canceled)

57-71. -71. (canceled)

74-84. -84. (canceled)

86-93. -93. (canceled)

95. (canceled)