IP Library Granted Patent US 10,071,186
Granted Patent B2
US 10,071,186 · App. 14/381,332 · Granted Sep 11, 2018

Glycosaminoglycan and synthetic polymer material for blood-contacting applications

Inventors: Susan P. James (Bellvue, CO); Harold Dean, IV (Ventura, CA); Lakshmi Prasad Dasi (Fort Collins, CO); Marcio H. Forleo (Fort Collins, CO); Ketul C. Popat (Fort Collins, CO); Nicole R. Lewis (Fort Collins, CO); David Alois Prawel (Loveland, CO)
Assignee: Colorado State University Research Foundation
A61L27/48A61F2/24A61L17/10A61L27/16A61L27/18A61L27/20A61L27/50A61L27/54A61L29/126A61L29/14A61L31/129A61L31/14A61L2300/236A61L2300/42A61L2300/62A61L2430/20
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Quick Facts
Patent No.
US 10,071,186
App. No.
14/381,332
Granted
Sep 11, 2018
Kind
B2
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 (34)

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 forming cross-linked guest molecules, such that the cross-linked guest molecules interpenetrate the polymer host molecule at a nanometer scale.

2. The composite of claim 1 , wherein the polymer host is a film with a thickness of 25 μm to 100 μm.

3. The composite of claim 2 , wherein the film has a thickness of 50 μm.

4. 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.

5. The composite of claim 1 , wherein the aqueous contact angle at the surface of the composite is 10° to 90°.

6. The composite of claim 5 , wherein the aqueous contact angle at the surface of the composite is 40° to 80°.

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

8. The composite of claim 7 , wherein the average molecular weight is 1 kDa to 10 kDa.

9. 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 forming cross-linked guest molecules, such that the cross-linked guest molecules interpenetrate the polymer host molecule at a nanometer scale.

10. The device of claim 9 , 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.

11. The device of claim 9 , wherein the composite, upon contact with blood, substantially reduces thrombogenesis and/or substantially improves endothelialization compared to the polymer host without a guest molecule disposed therein.

12. The heart valve of claim 10 , wherein the flow control member is a leaflet formed from the composite, and the polymer host is selected from the group consisting of low-density polyethylene (LDPE) film, linear low-density polyethylene (LLDPE) film, and polyethylene terephthalate (PET) fabric.

13. The heart valve of claim 12 , further comprising a suture ring or sewing cuff made from a second composite, the 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 forming cross-linked guest molecules, such that the cross-linked second guest molecules interpenetrate the second polymer host molecule at a nanometer scale.

14. The device of claim 9 , wherein the device is a small-diameter vascular graft formed from the composite, and the polymer host comprises expanded polytetrafluoroethylene (ePTFE).

15. The heart valve of claim 10 ,

the heart valve further comprising a suture ring made from the composite, the polymer host comprising PET fabric and

wherein the flow control member is a tilting disk formed from a second composite comprising:

a second polymer host comprising ultra-high molecular weight polyethylene (UHMWPE), 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 forming cross-linked guest molecules, such that the cross-linked second guest molecules interpenetrate the second polymer host molecule at a nanometer scale.

16. The device of claim 9 , wherein the device is a suture ring or sewing cuff made from the composite, and the polymer host comprises PET fabric.

Assignments (3)
CONFIRMATORY LICENSE Recorded Jun 17, 2021
From: COLORADO STATE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 056616/0179 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 27, 2014
From: JAMES, SUSAN P.; DEAN, HAROLD, IV; DASI, LAKSHMI PRASAD; FORLEO, MARCIO H.; POPAT, KETUL C.; LEWIS, NICOLE R.
To: COLORADO STATE UNIVERSITY RESEARCH FOUNDATION
Reel/Frame 033620/0134 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 27, 2014
From: PRAWEL, DAVID A.
To: COLORADO STATE UNIVERSITY RESEARCH FOUNDATION
Reel/Frame 033620/0197 →
Continuity (2)
Provisional Application 61609818 · Mar 12, 2012
Related Publication 20150196688A1 · Jul 16, 2015