Method of using a cardiovascular graft to reduce thrombosis or platelet adhesion
Inventors
Burke, Luke David • Cox, Martijn Antonius Johannes • Serrero, Aurelie
Assignees
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Publication Number
US-11980535-B2
Publication Date
2024-05-14
Expiration Date
Abstract
A cardiovascular graft is provided with highly reduced thrombogenicity. The cardiovascular graft is an electrospun non-woven mesh produced from supramolecular polymers with large diameter fibers. The cardiovascular graft can be implemented as a vascular graft into the human body to allow vascular bypass/reconstruction, or repeated venous access for dialysis treatment, as well as other disorders of small-diameter blood vessels.
Core Innovation
The invention relates to using a cardiovascular graft to reduce platelet adhesion upon implantation in a human body. The cardiovascular graft is designed as a tubular structure with an inner wall made out of a fibrous network of supramolecular compounds, in which hard-blocks comprise 2-ureido-4[1H]-pyrimidinone (UPy) compounds and are covalently bonded with soft-blocks. The fibrous network is a bioresorbable electrospun non-woven fibrous network with fibers having an average fiber diameter of 1-10 microns.
The tubular structure has an inner diameter between 2-8 mm and an inner wall thickness of 20-900 micrometers. The soft-blocks comprise polyurethane, polycarbonate, poly(ortho)ester, polyphosphoester, polyanhydride, polyphosphazene, polyhydroxyalkanoate, polyvinylalcohol, polypropylenefumarate, or any combination thereof. The invention focuses on configuring supramolecular hard-block/soft-block compositions within a bioresorbable electrospun tubular fibrous network.
The described approach addresses platelet adhesion and thrombogenicity, including platelet-driven thrombogenicity associated with cardiovascular graft implantation. In vitro and in vivo evidence reported in the document indicates that supramolecular polymer grafts substantially reduce platelet activation/adhesion and platelet-driven thrombogenicity versus PTFE, correlating platelet response with integrin αIIbβ3. Large-animal implantation studies reported in the document include sheep coronary bypass and carotid interposition grafts showing improved patency and reduced thrombus with platelet-inhibition regimens.
Claims Coverage
The independent claim is a method for using a cardiovascular graft to reduce platelet adhesion upon implantation in a human body, with the graft configured as an electrospun, bioresorbable tubular fibrous network using UPy-based supramolecular compounds. No additional independent claims were included in the provided claim list; therefore, inventive-feature extraction is limited to this single independent claim.
UPy hard-block covalently bonded to soft-blocks in a fibrous network
A cardiovascular graft designed as a tubular structure with an inner wall made out of a fibrous network of supramolecular compounds having hard-blocks covalently bonded with soft-blocks, wherein the hard-blocks comprise 2-ureido-4[1H]-pyrimidinone (UPy) compounds.
Bioresorbable electrospun non-woven fibrous network with specified fiber diameter
The fibrous network is a bioresorbable electrospun non-woven fibrous network with fibers having an average fiber diameter of 1-10 microns.
Tubular inner geometry constraints for inner diameter and wall thickness
The tubular structure has an inner diameter between 2-8 mm, and an inner wall thickness of 20-900 micrometers.
Specified soft-block polymer selection
The soft-blocks comprise a polyurethane, polycarbonate, poly(ortho)ester, polyphosphoester, polyanhydride, polyphosphazene, polyhydroxyalkanoate, polyvinylalcohol, polypropylenefumarate or any combination thereof.
Using the cardiovascular graft to reduce platelet adhesion upon implantation
Using the cardiovascular graft to reduce platelet adhesion upon implantation of the cardiovascular graft in a human body.
Overall claim coverage centers on an implanted tubular cardiovascular graft whose inner wall is a bioresorbable electrospun non-woven fibrous network built from UPy-based supramolecular compounds with UPy hard-blocks covalently bonded to specified soft-block polymers, with defined inner diameter, wall thickness, and fiber diameter to achieve reduced platelet adhesion.
Stated Advantages
Reducing platelet adhesion upon implantation of the cardiovascular graft in a human body.
Substantially reducing platelet activation/adhesion and platelet-driven thrombogenicity versus PTFE.
Improving patency and reducing thrombus in large-animal implantation studies.
Documented Applications
Use of an electrospun bioresorbable tubular cardiovascular graft to reduce platelet adhesion upon implantation in a human body.
Sheep coronary bypass graft implantation.
Carotid interposition graft implantation.
In vivo and in vitro evaluation of platelet activation/adhesion and platelet-driven thrombogenicity of the supramolecular polymer graft versus PTFE.
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