Yale University

Research Institute at Nationwide Children's Hospital

Pall Corporation

Children's National Medical Center

Nanofiber Solutions, LLC

Christopher K Breuer

Tarek M Fahmy

Narutoshi Hibino

Themis Kyriakides

Michael Simons

Pei-Yu Chen

Robert V Strouse

Cameron Best

Yong Ung-Lee

Jason Roh

Daniel Rowe Duncan

Joseph Patterson

Axel Krieger

Jed Johnson

Justin Opfermann

Martin Smith

Robert Strouse

Edward L Snyder

Keru O Shafi

Carolyn Cochenour Dorgan

Vidu Garg

Keru Shafi

Martin Alexander Smith

Methods for increasing the patency of biodegradable, synthetic vascular grafts are provided. The methods include administering one or more cytokines and/or chemokines that promote outward tissue remodeling of the vascular grafts and vascular neotissue formation. The disclosed methods do not require cell seeding of the vascular grafts, thus avoiding many problems associated with cell seeding. Biodegradable, polymeric vascular grafts which provide controlled release of cytokines and/or chemokines at the site of vascular graft implantation are also provided.

Compositions and methods for promoting patency of vascular grafts

It has been established that optimizing cell seeding onto tissue engineering vascular grafts (TEVG) is associated with reduced inflammatory responses and reduced post-operative stenosis of TEVG. Cell seeding increased TEVG patency in a dose dependent manner, and TEVG patency improved when more cells were seeded, however duration of incubation time showed minimal effect on TEVG patency. Methods of engineering patient specific TEVG including optimal numbers of cells to maintain graft patency and reduce post-operative stenosis are provided. Closed, single-use customizable systems for seeding TEVG are also provided. Preferably the systems are custom-designed based on morphology of the patient specific graft, to enhance the efficacy of cell seeding.

Systems and methods for optimized patient specific tissue engineering vascular grafts

A method for generating a electro spun fiber medical implant including determining dimensions of a portion of anatomy of a patient corresponding to the electro spun fiber medical implant via medical imaging, generating a model of the portion of the anatomy based on the dimensions, the model including one or more solid areas and one or more void areas encompassed within the one or more solid areas, inverting the model to generate a mandrel model, the mandrel model generated based on the one or more void areas, generating the mandrel based on the mandrel model, the mandrel including at least one electrically conductive material therein, and applying an electro-spinning process to the mandrel to generate the electro spun fiber medical implant which circumscribes the mandrel, wherein the mandrel is removable from within the electro spun fiber medical implant after a disassembly process.

Method for generating an electro spun fiber medical implant

A composition containing a macrophage inhibitor may be administered in an effective amount to prevent, inhibit or reduce restenosis, thrombus or aneurysm formation in implanted polymeric vascular grafts. The composition may be administered prior to vascular graft implantation, at the same time as vascular graft implantation, following vascular graft implantation, or any combination thereof. Examplary macrophage inhibitors include bisphosphonates, anti-folate drugs and antibodies, preferably in a controlled release or liposomal formulation.

Cell-free tissued engineered vascular grafts

Methods for treating or preventing neointima stenosis are disclosed. The methods generally involve the use of a TGF&#x3b2; inhibitor, a SMAD2 inhibitor, an FGF Receptor agonist, a Let-7 agonist, or a combination thereof, to inhibit endothelial-to-mesenchymal transition (Endo-MT) of vascular endothelial cells into smooth muscle cells (SMC) at sites of endothelial damage. The disclosed methods can therefore be used to prevent or inhibit neointimal stenosis or restenosis, e.g., after angioplasty, vascular graft, or stent. Also disclosed are methods for increasing the patency of biodegradable, synthetic vascular grafts using a composition that inhibits Endo-MT. A cell-free tissue engineered vascular graft (TEVG) produced by this method is also disclosed.

Compositions and methods for treating and preventing neointimal stenosis

A composition containing a macrophage inhibitor may be administered in an effective amount to prevent, inhibit or reduce restenosis, thrombus or aneurysm formation in implanted polymeric vascular grafts. The composition may be administered prior to vascular graft implantation, at the same time as vascular graft implantation, following vascular graft implantation, or any combination thereof. Exemplary macrophage inhibitors include bisphosphonates, anti-folate drugs and antibodies, preferably in a controlled release or liposomal formulation.

Cell-free tissue engineered vascular grafts

Systems are provided for convenient and sterile isolation, collection, and seeding of cells onto a scaffold or tissue graft. The systems may be closed. Methods for use of the disclosed systems for isolation, collection and seeding of cells and generation of tissue engineered vascular grafts are also provided. The systems may be supplied in kits for efficient and expeditious use.

System for seeding cells onto three dimensional scaffolds

Growing community of inventors

New Albany, OH, United States of America

Christopher K Breuer