Abstract: 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.

Abstract: Closed disposable seeding systems with improved seeding chambers permitting uniform seeding of a scaffold or graft with patient's cells are provided. The seeding chambers with a variable width along the length of the chamber, or a minimal gap between the scaffold and chamber wall, provide an improvement of the prior seeding chambers of closed disposable seeding systems by providing faster and more efficient and uniform seeding of the grafts and scaffolds. Also described are scaffolds with biomechanical and structural properties permitting spontaneous reversal of stenosis and neotissue formation as the graft degrades yielding a scaffold-free neovessel.

Abstract: 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.

Abstract: 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.

Abstract: Excessive or repeated activation of inflammatory and pro-coagulant mechanisms at the site of tissue injury contributes to the development scar tissue that can lead to intimal hyperplasia and fibrotic disease. It has been established that inhibition of the LYST protein is associated with reduced inflammatory responses and reduced platelet activation at the site of tissue damage. Compositions and methods for inhibition of the expression and function of the LYST protein are described. The compositions and methods can be useful for the modulation of immune processes that contribute to formation of neointima and fibroproliferative disorders by altering macrophage, platelet and natural killer cell function to create a pro-regenerative immune response.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Methods for treating or preventing neointima stenosis are disclosed. The methods generally involve the use of a TGF? 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.

Abstract: Excessive or repeated activation of inflammatory and pro-coagulant mechanisms at the site of tissue injury contributes to the development scar tissue that can lead to intimal hyperplasia and fibrotic disease. It has been established that inhibition of the LYST protein is associated with reduced inflammatory responses and reduced platelet activation at the site of tissue damage. Compositions and methods for inhibition of the expression and function of the LYST protein are described. The compositions and methods can be useful for the modulation of immune processes that contribute to formation of neointima and fibroproliferative disorders by altering macrophage, platelet and natural killer cell function to create a pro-regenerative immune response.

Abstract: Methods for treating or preventing neointima stenosis are disclosed. The methods generally involve the use of a TGF? 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.

Abstract: Methods for treating or preventing neointima stenosis are disclosed. The methods generally involve the use of a TGF? 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.

Abstract: 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.

Abstract: Methods for treating or preventing neointima stenosis are disclosed. The methods generally involve the use of a TGF? 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.

Abstract: 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.

Abstract: 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.