Anti-thrombogenic grafts

a graft and anti-thrombosis technology, applied in the field of anti-thrombosis grafts, can solve the problems of high thrombosis and reduce the effect of thrombosis, and achieve the effect of inducing growth and/or differentiation

Inactive Publication Date: 2018-08-30
YALE UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method for recellularizing a decellularized tissue by culturing cells on the surface of the substrate or coating. The cells can be induced to proliferate and differentiate throughout the composition. The number of cells and the type of cells used can vary depending on the organ or tissue being recellularized. The cells can be introduced into the decellularized organ or tissue through injection or perfusion. The recellularization process involves maintaining the organ or tissue under suitable conditions for cell growth and differentiation. The cells can be allogeneic or xenogeneic to the decellularized organ or tissue. The technical effect of the invention is the ability to recellularize decellularized tissue and create functional organs or tissues.

Problems solved by technology

Currently their main drawback is high thrombogenicity, which can be reduced by recellularizing the luminal side of the implant with host cells.
However, this solution implies at least a one month patient specific waiting time, due to required harvest and expansion of autologous endothelial cells to line the graft lumen.

Method used

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Examples

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experimental examples

[0142]The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

[0143]Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure.

example 1

Hyaluronic Acid—Heparin Based Coatings for Biological Substrates

[0144]Described herein is the development of a coating for decellularized biological structures (native and tissue engineered) built from a first layer of thiol-modified hyaluronic acid (HA; also known as hyaluronan) and a second layer of modified heparin.

[0145]HA Coating

[0146]Thiol-modified HA (Glycosan, San Francisco, USA) was crosslinked onto decellularized biological structures amines groups (NH2) using the sulfhydryl (SH) groups on the HA. This was accomplished via heterobifunctional crosslinker made up of N-hydroxysuccinimide ester (NHS) and maleimide where NHS reacts with the amine groups on the decellularized vessels and maleimide reacted with the sulfhydryl groups on the hyaluronic acid. The crosslinked hyaluronic acid created a few microns thick continuous layer over the length of the tubular vessel, “hiding” the exposed collagen of decellularized vessels.

[0147]Heparin Modification and Modified Heparin Coating...

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Abstract

The present invention provides anti-thrombogenic compositions, including anti-thrombogenic vascular grafts. In certain embodiments, the compositions comprise decellularized tissue coated with an anti-thrombogenic coating. The present invention also provides methods of preparing anti-thrombogenic compositions and methods of treatment comprising implanting the anti-thrombogenic compositions into a subject in need thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]The present application is a continuation of U.S. patent application Ser. No. 14 / 783,897, filed Oct. 12, 2015, which is a 35 U.S.C. § 371 national phase application of, and claims priority to, International Application No. PCT / US2014 / 038597, filed May 19, 2014, and published under PCT Article 21(2) in English, which claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 61 / 825,256, filed May 20, 2013, all of which application s are incorporated herein by reference in their entireties.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under HL083895 awarded by National Institute of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Vascular grafting is the use of transplanted blood vessels or synthetic scaffolds to replace, repair, or bypass damaged or potentially dangerous vessels. Vascular grafts are impl...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61L27/50A61K31/727A61L27/34A61L27/36A61L27/52A61L33/00B05D7/00A61L33/08A61L27/54A61K35/44
CPCB05D7/54A61K31/727A61L27/52A61L33/0064A61L33/08A61K35/44A61L2420/02A61L2420/08A61L2300/608A61L2300/42A61L2300/236A61L33/0029A61L33/0011A61L27/54A61L27/507A61L27/3625A61L27/34A61L2430/40C08B37/0072C08B37/0075C09D105/08C09D105/10C08L5/08
InventorDIMITRIEVSKA, SASHKANIKLASON, LAURA
OwnerYALE UNIV