Graft with expandable region and methods of making and using the same

Abstract

To provide a favorable graft with an expandable region, and favorable methods of making and using the same.SOLUTION: A vascular graft suitable for implantation having an expandable outflow region 42 for restoring the patency of the graft after implantation into a body lumen. A graft comprises a conduit having a wall. The conduit includes at least one inflow aperture at an inflow end of a body region, and an outflow aperture at an outflow end of an outflow region opposite from the at least one inflow aperture. The wall includes a support structure and a biocompatible layer. The support structure along the outflow region is under continuous compressive stress resulting from a continuous applied load caused by the biocompatible layer against the support structure.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the benefit of priority based on U.S. Provisional Patent Application No. 61 / 857,181, filed on July 22, 2013, the content of which is hereby incorporated by reference in its entirety herein.

[0002] (Field of the Invention) The present invention and disclosure relate to various embodiments of vascular grafts suitable for transplantation (including the manufacture and use of such grafts). In certain embodiments of the present disclosure, one or more expandable first regions are provided to restore the patency of the graft after transplantation into a body lumen.

Background Art

[0003] (Background of the Invention) Vascular diseases are widespread throughout the world. Bypass surgery, in which a conduit, either artificial or autologous, is transplanted into an existing blood vessel to bypass an affected portion of the vasculature or to restore blood flow around an occluded or damaged blood vessel, is one of the most common treatments for such diseases.

[0004] Vascular grafts are also used as access sites in dialysis patients. The graft connects or bridges an artery and a vein within the patient's body. A needle is inserted into the graft to allow blood to be withdrawn, passed through a hemodialysis machine, and returned to the patient through a second needle inserted into the graft.

[0005] A significant number of bypass grafts fail within 5 - 7 years. The average lifespan of a hemodialysis graft is often even shorter, less than 2 years. The main cause of graft failure is occlusion of the graft due to intimal hyperplasia and ultimately thrombosis. The smaller the graft diameter, the higher the graft failure rate. The lost patency resulting from graft occlusion or collapse is particularly problematic at the outflow site where the outflow end of the graft touches the blood vessel.

[0006] However, this problem is typically not adequately addressed by conventional techniques for restoring patency that include surgical procedures (e.g., thrombectomy or percutaneous thrombectomy) or chemical intervention techniques (e.g., administration of anticoagulant or antiplatelet drugs such as ticlopidine, aspirin, dipyridamole, or clopidogrel) for removing internal growth tissue or clot that could otherwise contribute to graft failure. In particular, surgery and chemical intervention can introduce unnecessary risks (e.g., infections, bleeding, etc.) and are often inappropriate for maintaining patency over longer time periods.

[0007] Accordingly, there is a need for a graft that can readily restore patency after transplantation without requiring risky and ineffective chemical or surgical intervention. There is also a need for different graft structures that utilize various features of the graft technology disclosed herein. SUMMARY OF THE INVENTION MEANS FOR SOLVING THE PROBLEM

[0008] (Abstract) There is a need for a vascular graft having an expandable outflow region that enables easy restoration of patency after transplantation without requiring risky and ineffective chemical or surgical intervention. Embodiments of the present disclosure and invention are directed to further solutions for addressing the foregoing need in addition to having other desirable characteristics.

[0009] According to an embodiment of the present invention, a graft is provided. The graft includes a conduit having a wall. The conduit includes at least one inflow opening at an inflow end of a body region and an outflow opening at an outflow end of an outflow region opposite the at least one inflow opening. The wall includes a support structure and a biocompatible layer. The support structure along the outflow region is under a continuous compressive stress resulting from a continuous applied load generated by the biocompatible layer against the support structure.

[0010] According to an aspect of the present invention, the compressive stress resulting from the continuously applied load within the outflow region exceeds the compressive stress resulting from the continuously applied load within the body region. According to an aspect of the present invention, the compressive stress covered by the support structure resulting from the continuously applied load within the outflow region gradually increases in each section along the support structure that gradually becomes more distal from at least one inflow opening. The compressive stress covered by the support structure resulting from the continuously applied load within the outflow region causes an elastic deformation of the support structure within the outflow region. According to an aspect of the present invention, the elastic deformation of the support structure within the outflow region gradually becomes greater in each section along the support structure that gradually becomes more distal from at least one inflow opening. The elastic deformation of the support structure within the outflow region is reversible. The compressive stress resulting from the continuously applied load within the body region does not elastically deform the support structure within the body region.

[0011] According to an aspect of the present invention, the support structure has a plurality of effective outer diameter dimensions prior to forming the wall in combination with the biocompatible layer, and after forming the wall in combination with the biocompatible layer, the support structure has a substantially uniform effective outer diameter dimension. The plurality of effective outer diameter dimensions along the body region can be effective outer diameter dimensions that are constant. The plurality of effective outer diameter dimensions along the outflow region can be effective outer diameter dimensions that gradually increase in each section along the support structure that gradually becomes more distal from at least one inflow opening. The substantially uniform effective outer diameter dimension can have a constant effective outer diameter dimension along the body region and a constrained effective outer diameter dimension along the outflow region. The constrained effective outer diameter dimension is approximately equal to the constant effective outer diameter dimension. The compressive stress resulting from the continuously applied load maintains the support structure along the outflow region at the constrained effective outer diameter dimension.

[0012] According to an aspect of the present invention, a reaction force with a radially expanding force applied to a support structure along an outflow region causes plastic deformation of the biocompatible layer. A reaction force with a radially expanding force applied to a support structure within the outflow region causes a reduction in the compressive stress covered by the support structure. Following the application of a reaction force with a radially expanding force applied to the support structure within the outflow region, the graft is reconfigured to provide a plastically deformed biocompatible layer and a compressive stress covered by the support structure that is less than the compressive stress covered by the support structure prior to the application of the reaction force. Following the application of a reaction force with a radially expanding force applied to the support structure within the outflow region, the graft is reconfigured to provide a plastically deformed biocompatible layer. Following the application of a reaction force with a radially expanding force applied to the support structure within the outflow region, the graft is reconfigured to provide a support structure that bears a residual compressive stress if there was a continuous compressive stress covered by the support structure prior to the application of the reaction force.

[0013] According to an aspect of the present invention, a reaction force with a radially expanding force applied to a support structure within the outflow region reconfigures the support structure along the outflow region from a constrained effective outer diameter dimension to an expanded effective outer diameter dimension that exceeds the constrained effective outer diameter dimension along at least a portion of the support structure within the outflow region. According to an aspect of the present invention, the expanded effective outer diameter dimension exceeds the constrained effective outer diameter dimension by at least 1 mm along at least a portion of the support structure within the outflow region. According to an aspect of the present invention, the expanded effective outer diameter dimension of the support structure along the outflow region, after being reconfigured, exceeds the constrained effective outer diameter dimension by at least 1 mm along the entire portion of the support structure within the outflow region.

[0014] According to a further aspect of the present invention, the conduit can include a second inflow opening. The longitudinal axis of the second inflow opening intersects the longitudinal axis of at least one inflow opening at a non-parallel angle. According to an aspect of the present invention, the non-parallel angle comprises an angle of about 25° to 45°. According to one aspect of the present invention, the non-parallel angle is about 35°.

[0015] According to an aspect of the present invention, the support structure is constructed from a shape memory alloy. According to one aspect of the present invention, the support structure is constructed from nitinol. The support structure can have a zigzag wire shape.

[0016] According to an aspect of the present invention, the biocompatible layer comprises an expandable polymer. The biocompatible layer can include ePTFE. The biocompatibility can include a biocompatible outer layer. The biocompatible layer can include a biocompatible inner layer. The biocompatible outer layer and the biocompatible inner layer enclose the support structure. According to one aspect of the present invention, the biocompatible layer is not a surface modification coating.

[0017] According to one exemplary embodiment, a vascular graft is provided. The vascular graft includes a conduit having a wall. The wall includes at least one inflow opening at the inflow end of the body region and an outflow opening at the outflow end of the outflow region opposite the at least one inflow opening. The wall includes a support structure and a biocompatible layer. In combination with the biocompatible layer and prior to forming the wall, the support structure includes a plurality of effective outer diameter dimensions along its length. The plurality of effective outer diameter dimensions includes a constant effective outer diameter dimension along the body region and an effective outer diameter dimension along the outflow region that gradually increases in each section along the support structure that becomes gradually more distal from the at least one inflow opening. After forming the wall in combination with the biocompatible layer, the support structure within the outflow region is under a compressive stress resulting from a continuous applied load exerted by the biocompatible layer that maintains the support structure along the outflow region at a constrained effective outer diameter dimension that does not gradually increase in each section along the support structure that becomes gradually more distal from the at least one inflow opening. After application of a reaction force to the support structure within the outflow region, the support structure within the outflow region is reconfigured from the constrained effective outer diameter dimension to an expanded effective outer diameter dimension in which at least a portion thereof exceeds the constrained effective outer diameter dimension by at least one millimeter.

[0018] According to an exemplary embodiment of the present invention, a method for expanding an outflow end of a transplanted graft is provided. The method includes (a) identifying the transplanted graft and (b) applying a reaction force. The vascular graft includes a conduit having a wall. The conduit includes at least one inflow opening at an inflow end of a body region and an outflow opening at an outflow end of an outflow region opposite the at least one inflow opening. The wall includes a support structure and a biocompatible layer. Prior to forming the wall in combination with the biocompatible layer, the support structure has a plurality of effective outer diameter dimensions including a constant effective outer diameter dimension along the body region and an effective outer diameter dimension along the outflow region that gradually increases in each section along the support structure that is gradually more distal from the at least one inflow opening. After forming the wall in combination with the biocompatible layer, the support structure within the outflow region is under a compressive stress resulting from a continuously applied load caused by the biocompatible layer that maintains the support structure within the outflow region at a constrained effective outer diameter dimension that does not gradually increase in each section along the support structure that is gradually more distal from the at least one inflow opening. Applying a reaction force to the support structure within the outflow region reconfigures the support structure along the outflow region from the constrained effective outer diameter dimension to an expanded effective outer diameter dimension that exceeds the constrained effective outer diameter dimension, thereby expanding the outflow region of the transplanted graft.

[0019] According to an aspect of the present invention, the outflow region includes an outflow end that is crushed, stenotic, or has persistent intimal hyperplasia. An outflow end that is crushed, stenotic, or has a persistent intimal hyperplasia end impairs the patency of the vessel into which the graft is transplanted.

[0020] According to an aspect of the present invention, the step of applying a reaction force includes expanding an expandable device within the outflow region of the transplanted graft. Prior to expansion of the expandable device, the expandable device is advanced into the outflow region. Prior to advancement of the expandable device into the outflow region, the expandable device is introduced percutaneously into the transplanted graft.

[0021] According to an aspect of the present invention, the expanded effective outer diameter dimension is at least 1 millimeter greater than the constrained effective outer diameter dimension. According to an aspect of the present invention, the expanded effective outer diameter dimension is at least 1 millimeter greater than the constrained effective outer diameter dimension along any portion of the support structure within the outflow region.

[0022] According to one exemplary embodiment, a method of expanding the outflow region of a transplanted graft is provided. The method includes (a) providing a transplanted graft having an expandable outflow region, and (b) applying a reaction force to the outflow region. The transplanted graft includes a conduit having a wall. The conduit includes at least one inflow opening at an inflow end of a body region and an outflow opening at an outflow end of the outflow region opposite the at least one inflow opening. The wall includes a support structure and a biocompatible layer. The support structure within the outflow region is under a compressive stress resulting from an applied load caused by the biocompatible layer. The step of applying a reaction force to the support structure within the outflow region reconfigures the support structure along the outflow region from a constrained effective outer diameter dimension to an expanded effective outer diameter dimension that is greater than the constrained effective outer diameter dimension, thereby expanding the outflow end of the transplanted graft.

[0023] According to an exemplary embodiment of the present invention, a method of making a graft having an expandable outflow end is provided. The method includes the step of providing a support structure having at least one inflow opening at an inflow end of a body region and an outflow opening at an outflow end of an outflow region opposite the at least one inflow opening. The support structure has a plurality of effective outer diameter dimensions including a constant effective outer diameter dimension along the body region of the support structure and a gradually increasing effective outer diameter dimension along the outflow region of the support structure. The method further includes the step of combining the support structure with at least one biocompatible layer to form a wall comprising the support structure and the at least one biocompatible layer. The method further includes the step of inserting a mandrel into the outflow opening proximal to the outflow end of the support structure. The method further includes the step of using compression winding to constrain the gradually increasing effective outer diameter dimension proximal to the outflow region of the support structure such that a continuous compressive stress results from a continuous applied load generated by the biocompatible layer and maintains the support structure along the outflow region at a constant effective outer diameter dimension and a uniformly constrained effective outer diameter dimension. The method further includes the step of sintering at least one biocompatible layer in a section within the outflow region. This specification also provides, for example, the following items. (Item 1) A graft, comprising a conduit having a wall, the conduit comprising a first vascular insertion region, a second vascular insertion region, and a connection region providing fluid communication therebetween, wherein the first and second vascular insertion regions each a first fluid flow region, and a second fluid flow region that both converge at a junction in fluid communication with an expandable third fluid flow region opposite the first fluid flow region. A first opening disposed at the outermost end of the first fluid flow region, a second opening disposed at the outermost end of the second fluid flow region, and a third opening disposed at the outermost end of the third fluid flow region, wherein the second openings of the first and second vascular insertion regions are interconnected via the connection region in a manner that enables fluid communication therebetween, the first opening, the second opening, and the third opening; comprising; wherein the wall comprises a support structure and a biocompatible layer, and a graft in which at least a portion of the support structure along at least a portion of the third fluid flow region of the first vascular insertion region is under a continuous compressive stress resulting from a continuous applied load exerted by the biocompatible layer on the support structure. (Item 2) The graft according to Item 1, wherein at least a portion of the support structure along at least a portion of the third fluid flow region of the second vascular insertion region is under a continuous compressive stress resulting from a continuous applied load exerted by the biocompatible layer on the support structure. (Item 3) The graft according to Items 1-2, wherein the compressive stress resulting from the continuous applied load in the third fluid flow region exceeds the compressive stress resulting from the continuous applied load in either the first fluid flow region or the second fluid flow region. (Item 4) The graft according to Items 1-2, wherein the compressive stress borne by the support structure resulting from the continuous applied load in the third fluid flow region gradually decreases in each section along the support structure until it is substantially constant near the junction. (Item 5) The graft according to Items 1-2, wherein the compressive stress borne by the support structure resulting from the continuous applied load in the third fluid flow region is substantially constant within the third fluid flow region and then gradually increases in each section along the support structure that becomes gradually more distal from the first opening, causing an elastic deformation of the support structure. (Item 6) The elastic deformation of the support structure within the third fluid flow region is reversible such that reversing the elastic deformation of the support structure within the third fluid flow region expands the diameter of the support structure within the third fluid flow region to a diameter less than the uncompressed diameter of the support structure that is not under the compressive stress resulting from the continuous applied load within the third fluid flow region, the graft of item 5. (Item 7) The elastic deformation of the support structure within the first fluid flow region due to the compressive stress resulting from the continuous applied load within the first fluid flow region is at most negligible, the graft of items 1-2. (Item 8) The elastic deformation of the support structure within the second fluid flow region due to the compressive stress resulting from the continuous applied load within the second fluid flow region is at most negligible, the graft of items 1-2. (Item 9) In combination with the biocompatible layer and prior to forming the wall, the support structure along the first fluid flow region has a constant effective inner diameter dimension, and the support structure along the third fluid flow region has an effective inner diameter dimension that is substantially constant before gradually increasing in each section along the support structure that becomes gradually more distal from the first opening, the graft of items 1-2. (Item 10) After forming the wall in combination with the biocompatible layer, the support structure has a substantially uniform effective inner diameter dimension comprising a constant effective inner diameter dimension along the first fluid flow region and a constrained effective inner diameter dimension along the third fluid flow region, the graft of item 9. (Item 11) The constrained effective inner diameter dimension is approximately equal to the constant effective inner diameter dimension, the graft of item 10. (Item 12) The compressive stress resulting from the continuous applied load maintains the support structure along the third fluid flow region at the constrained effective inner diameter dimension, the graft of item 11. (Item 13) The graft according to item 12, wherein a reaction force having a radially expanding force applied to the support structure along the third fluid flow region causes permanent deformation of the biocompatible layer. (Item 14) The graft according to item 13, wherein a reaction force having a radially expanding force applied to the support structure within the third fluid flow region causes a reduction in the compressive stress covered by the support structure. (Item 15) Following the application of a reaction force having a radially expanding force applied to the support structure within the third fluid flow region, the graft is reconfigured to result in a permanently deformed biocompatible layer and a compressive stress covered by the support structure that is less than the compressive stress covered by the support structure prior to the application of the reaction force, as described in item 14. (Item 16) Following the application of a reaction force having a radially expanding force applied to the support structure within the third fluid flow region, the graft is reconfigured such that the support structure results in covering a reduced compressive stress that was previously greater and was covered by the support structure prior to the application of the reaction force, as described in item 15. (Item 17) The graft according to item 16, wherein a reaction force having a radially expanding force applied to the support structure within the third fluid flow region reconfigures the support structure along the third fluid flow region from the constrained effective inner diameter dimension to an expanded effective inner diameter dimension that exceeds the constrained effective inner diameter dimension along at least a portion of the support structure within the third fluid flow region. (Item 18) The graft according to item 17, wherein the expanded effective inner diameter dimension exceeds the constrained effective inner diameter dimension by at least 1 mm along at least a portion of the support structure within the third fluid flow region. (Item 19) The graft according to item 18, wherein the effective inner diameter dimension of the support structure along the third fluid flow region is greater than the constrained effective inner diameter dimension along an adjacent portion of the support structure within the third fluid flow region. (Item 20) The graft according to items 1-2, wherein at least the expandable third fluid flow region within the first vascular insertion region comprises an elongate expandable third fluid flow region. (Item 21) The graft according to item 1 or 20, wherein the expandable third fluid flow region within the second vascular insertion region comprises an elongate expandable third fluid flow region. (Item 22) The graft according to items 20-21, wherein the elongate expandable third fluid flow region has a length that exceeds about 5 times the length of either the first fluid flow region or the second fluid flow region. (Item 23) The graft according to items 20-21, wherein the length of the conduit between the junction and the outermost end of the third fluid flow region exceeds the combined length of the first fluid flow region and the second fluid flow region. (Item 24) The graft according to items 20-21, wherein the length of the conduit between the junction and the outermost end of the third fluid flow region is at least about 50 millimeters. (Item 25) The graft according to items 20-21, wherein the compressive stress covered by the support structure resulting from a continuously applied load within the elongate expandable third fluid flow region gradually decreases in one or more initial sections along the support structure before becoming substantially constant across each section that becomes progressively more distal from the third fluid flow region. (Item 26) The graft according to items 20-21, wherein the compressive stress covered by the support structure resulting from a continuously applied load within the elongate expandable third fluid flow region gradually increases in one or more initial sections along the support structure before becoming substantially constant across each section that becomes progressively more distal from the third fluid flow region, causing an elastic deformation of the support structure within the elongate expandable third fluid flow region. (Item 65) The elastic deformation of the support structure within the elongate expandable third fluid flow region is reversible such that reversing the elastic deformation of the support structure within the elongate expandable third fluid flow region expands the diameter of the support structure within the elongate expandable third fluid flow region to a diameter less than the uncompressed diameter of the support structure that is not under compressive stress resulting from the continuous applied load within the elongate expandable third fluid flow region, the graft of item 58 or 59. (Item 27) The elastic deformation of the support structure within the first and second fluid flow regions due to compressive stress resulting from the continuous applied load within the first and second fluid flow regions is at most negligible, the graft of items 20 - 21. (Item 28) In combination with the biocompatible layer and prior to forming the wall, the support structure within the first vascular insertion region has a constant effective inner diameter dimension along the first fluid flow region and an effective inner diameter dimension along the third fluid flow region that gradually decreases in one or more initial sections along the support structure before becoming constant across sections that become increasingly distal from the one or more initial sections, the graft of items 20 - 21. (Item 29) In combination with the biocompatible layer and prior to forming the wall, the support structure within the second vascular insertion region has a constant effective inner diameter dimension along the first fluid flow region and an effective inner diameter dimension along the third fluid flow region that gradually decreases in one or more initial sections along the support structure before becoming constant across sections that become increasingly distal from the one or more initial sections, the graft of items 20 - 21. (Item 30) After forming the wall in combination with the biocompatible layer, the support structure within the first vascular insertion region has a substantially uniform effective inner diameter dimension comprising a constant effective inner diameter dimension along the first fluid flow region and a constrained effective inner diameter dimension along the elongate expandable third fluid flow region, the graft of items 20 - 21. (Item 31) In combination with the biocompatible layer, after forming the wall, the support structure within the second vascular insertion region comprises a constant effective inner diameter dimension along the first fluid flow region and a constrained effective inner diameter dimension along the elongated expandable third fluid flow region, and has a substantially uniform effective inner diameter dimension, the graft according to items 20-21. (Item 32) The constrained effective inner diameter dimension is substantially equal to the constant effective inner diameter dimension, the graft according to items 30-31. (Item 33) The compressive stress resulting from the continuously applied load maintains the support structure along the elongated expandable third fluid flow region at the constrained effective inner diameter dimension, the graft according to item 32. Graft. (Item 34) The reaction force with a radially expanding force applied to the support structure along the elongated expandable third fluid flow region causes permanent deformation of the biocompatible layer, the graft according to item 33. (Item 35) The reaction force with a radially expanding force applied to the support structure within the elongated expandable third fluid flow region causes a decrease in the compressive stress borne by the support structure, the graft according to item 34. (Item 36) Following the application of the reaction force with a radially expanding force applied to the support structure within the elongated expandable third fluid flow region, the graft is reconfigured to provide a permanently deformed biocompatible layer and a compressive stress borne by the support structure that is less than the compressive stress borne by the support structure prior to the application of the reaction force, the graft according to item 35. (Item 37) Following the application of the reaction force with a radially expanding force applied to the support structure within the elongated expandable third fluid flow region, the graft is reconfigured to provide a support structure that bears a reduced compressive stress that was previously greater prior to the application of the reaction force, the graft according to item 36. (Item 38) The reaction force with a radially expanding force applied to the support structure within the elongated expandable third fluid flow region is from the constrained effective inner diameter dimension to an expanded effective inner diameter dimension that exceeds the constrained effective inner diameter dimension along at least a portion of the support structure within the elongated expandable third fluid flow region, restructuring the support structure along the elongated expandable third fluid flow region, the graft according to item 37. (Item 39) The expanded effective inner diameter dimension exceeds the constrained effective inner diameter dimension along at least a portion of the support structure within the elongated expandable third fluid flow region by at least 1 mm, the graft according to item 38. (Item 40) After restructuring, the expanded effective inner diameter dimension of the support structure along the elongated expandable third fluid flow region exceeds the constrained effective inner diameter dimension by at least 1 mm along most of the support structure within the elongated expandable third fluid flow region, the graft according to item 39. (Item 41) The longitudinal axis of the second fluid flow region intersects the longitudinal axis of the first fluid flow region at a non-parallel angle, the graft according to item 1. (Item 42) The non-parallel angle is an angle of about 25° to 45°, the graft according to item 41. (Item 43) The non-parallel angle is an angle of about 35°, the graft according to item 41. (Item 44) The second fluid flow region merges together at the junction with the first fluid flow region such that the first fluid flow region and the second fluid flow region are not perpendicular to each other, the graft according to item 1. (Item 45) The support structure is constructed from a shape memory alloy, the graft according to item 1. (Item 46) The support structure is constructed from nitinol, the graft according to item 1. (Item 47) The graft according to item 1, wherein the biocompatible layer comprises an expandable polymer. (Item 48) The graft according to item 1, wherein the biocompatible layer comprises ePTFE. (Item 49) The graft according to item 1, wherein the biocompatible layer further comprises a biocompatible outer layer. (Item 50) The graft according to item 49, wherein the biocompatible layer further comprises a biocompatible inner layer. (Item 51) The graft according to item 50, wherein the biocompatible outer layer and the biocompatible inner layer enclose the support structure. (Item 52) The graft according to item 1, wherein the biocompatible layer is not a surface modification coating. (Item 53) A graft comprising: A conduit having a wall, the conduit comprising: A first inflow region having a first inflow end and a second inflow region having a second inflow end, the first and second inflow regions merging together at an inflow junction that fluidly communicates with an elongated expandable outflow region opposite the first inflow region, the outflow region having an outflow end, the first and second inflow regions, A first inflow opening disposed at the first inflow end of the first inflow region, a second inflow opening disposed at the second inflow end of the second inflow region, and an outflow opening disposed at the outflow end of the outflow region, Comprising: Wherein the wall comprises a support structure and a biocompatible layer, At least a portion of the support structure along the elongated expandable outflow region is under a compressive stress resulting from an applied load caused by the biocompatible layer on the support structure, and The length of the elongated expandable outflow region exceeds twice the length of either the first inflow region or the second inflow region. (Item 54) The graft according to item 53, wherein the elongated expandable outflow region has a length exceeding the length of either the first inflow region or the second inflow region. (Item 55) The graft according to item 53, wherein the length of the conduit between the inflow junction and the outflow end is at least about 100 millimeters. (Item 56) The graft according to item 53, wherein the compressive stress resulting from a continuously applied load within the elongated expandable outflow region exceeds the compressive stress resulting from a continuously applied load within either the first inflow region or the second inflow region. (Item 57) The graft according to item 53, wherein the compressive stress shielded by the support structure resulting from a continuously applied load within the elongated expandable outflow region gradually increases in one or more initial sections along the support structure before becoming substantially constant across sections that gradually become more distal from the one or more initial sections. (Item 58) The graft according to item 53, wherein the compressive stress shielded by the support structure resulting from a continuously applied load within the elongated expandable outflow region causes an elastic deformation of the support structure within the elongated expandable outflow region. (Item 59) The graft according to item 58, wherein the elastic deformation of the support structure within the outflow region increases in one or more initial sections along the support structure before becoming substantially constant across sections that gradually become more distal from the one or more initial sections. (Item 60) The graft according to item 58, wherein the elastic deformation of the support structure within the elongated expandable outflow region is reversible. (Item 61) Reversing the elastic deformation of the support structure within the elongated expandable outflow region expands the diameter of the support structure within the elongated expandable outflow region to a diameter greater than the uncompressed diameter of the support structure not under the compressive stress resulting from a continuously applied load within the elongated expandable outflow region. The graft according to item 53. (Item 62) The elastic deformation of the support structure in the second inflow region due to the compressive stress resulting from the continuously applied load within the second inflow region is negligible at most, the graft according to item 53. (Item 63) The elastic deformation of the support structure in the first inflow region due to the compressive stress resulting from the continuously applied load within the first inflow region is negligible at most, the graft according to item 53. (Item 64) The support structure, in combination with the biocompatible layer, has a plurality of effective inner diameter dimensions prior to forming the wall, and after forming the wall in combination with the biocompatible layer, the support structure has a substantially uniform effective inner diameter dimension, the graft according to item 53. (Item 65) The effective inner diameter dimension along the first inflow region has a constant effective inner diameter dimension, the graft according to item 64. (Item 66) The effective inner diameter dimension prior to combination with the biocompatible layer along the elongated expandable outflow region increases along one or more initial sections along the support structure before becoming constant across each section that becomes increasingly distal from the one or more initial sections, the graft according to item 64. (Item 67) The substantially uniform effective inner diameter dimension after combination with the biocompatible layer has a constant effective inner diameter dimension along the first inflow region and a constrained effective inner diameter dimension along the elongated expandable outflow region, the graft according to item 64. (Item 68) The constrained effective inner diameter dimension is approximately equal to the constant effective inner diameter dimension, the graft according to item 67. (Item 69) The compressive stress resulting from the continuously applied load maintains the support structure along the elongated expandable outflow region at the constrained effective inner diameter dimension, the graft according to item 67. (Item 70) The graft according to item 67, wherein the reaction force having a radially expanding force applied to the support structure along the elongated expandable outflow region causes a permanent deformation of the biocompatible layer. (Item 71) The graft according to item 67, wherein the reaction force having a radially expanding force applied to the support structure within the elongated expandable outflow region causes a reduction in the compressive stress covered by the support structure. (Item 72) Following the application of the reaction force having a radially expanding force applied to the support structure within the elongated expandable outflow region, the graft is reconfigured to provide a permanently deformed biocompatible layer and a compressive stress covered by the support structure that is less than the compressive stress covered by the support structure prior to the application of the reaction force, according to item 67. (Item 73) Following the application of the reaction force having a radially expanding force applied to the support structure within the elongated expandable outflow region, the graft is reconfigured to provide a permanently deformed biocompatible layer, according to item 67. (Item 74) Following the application of the reaction force having a radially expanding force applied to the support structure within the elongated expandable outflow region, the graft is reconfigured to provide a support structure that covers a reduced compressive stress that was previously greater and covered by the support structure prior to the application of the reaction force, according to item 67. (Item 75) The graft according to item 67, wherein the reaction force having a radially expanding force applied to the support structure within the elongated expandable outflow region reconfigures the support structure along the elongated expandable outflow region from the constrained effective inner diameter dimension to an expanded effective inner diameter dimension that exceeds the constrained effective inner diameter dimension along at least a portion of the support structure within the elongated expandable outflow region. (Item 76) The graft according to item 75, wherein the expanded effective inner diameter dimension exceeds the constrained effective inner diameter dimension by at least 1 mm along at least a portion of the support structure within the elongated expandable outflow region. (Item 77) The expanded effective inner diameter dimension of the support structure along the elongated expandable outflow region, after reconstruction, is at least 1 mm greater than the constrained effective inner diameter dimension along most of the support structure within the elongated expandable outflow region, the graft according to Item 75. (Item 78) The longitudinal axis of the second inflow region intersects the longitudinal axis of the first inflow region at a non-parallel angle, the graft according to Item 53. (Item 79) The non-parallel angle comprises an angle of about 25° to 45°, the graft according to Item 78. (Item 80) The non-parallel angle comprises an angle of about 35°, the graft according to Item 78. (Item 81) The second inflow region merges together at the inflow junction with the first inflow region such that the first inflow region and the second inflow region are not perpendicular to each other, the graft according to Item 78. (Item 82) The support structure is constructed from a shape memory alloy, the graft according to Item 53. (Item 83) The support structure is constructed from nitinol, the graft according to Item 53. (Item 84) The biocompatible layer comprises an expandable polymer, the graft according to Item 53. (Item 85) The biocompatible layer comprises ePTFE, the graft according to Item 53. (Item 86) The biocompatible layer further comprises a biocompatible outer layer, the graft according to Item 53. (Item 87) The biocompatible layer further comprises a biocompatible inner layer, the graft according to Item 86. (Item 88) The biocompatible outer layer and the biocompatible inner layer encapsulate the support structure, the graft according to Item 87. (Item 89) The biocompatible layer is the graft according to item 88 that is not a surface modification coating. (Item 90) The support structure is the graft according to item 88 that is constructed from a shape memory alloy. (Item 91) The support structure is the graft according to item 88 that is constructed from nitinol. (Item 92) A graft comprising: A conduit having a wall, the conduit comprising: A first vascular insertion region, a second vascular insertion region, and a connection region providing fluid communication therebetween; The first vascular insertion region: A first fluid flow region and a second fluid flow region that both merge at a junction that is in fluid communication with a third fluid flow region opposite the first fluid flow region; A first opening disposed at the outermost end of the first fluid flow region, a second opening disposed at the outermost end of the second fluid flow region, and a third opening disposed at the outermost end of the third fluid flow region; And comprising: The second vascular insertion region: A fourth fluid flow region extending from a fourth opening disposed adjacent to the connection region to a fifth opening disposed opposite adjacent to the terminal portion of the second vascular insertion region, the second opening of the first vascular insertion region being connected to the fourth opening of the second vascular insertion region via the connection region in a manner that enables fluid communication therebetween; And comprising: Wherein the wall comprises a support structure and a biocompatible layer, and At least a portion of the support structure along the third fluid flow region is under a continuous compressive stress resulting from a continuous applied load exerted by the biocompatible layer on the support structure. (Item 93) The compressive stress resulting from the continuously applied load within the third fluid flow region exceeds the compressive stress resulting from the continuously applied load in either the first fluid flow region or the second fluid flow region, the graft according to item 92. (Item 94) The compressive stress covered by the support structure resulting from the continuously applied load in the third fluid flow region gradually increases in each section along the support structure that becomes gradually more distal from the first opening, and the stress becomes substantially constant proximal to the joint, the graft according to item 92. (Item 95) The compressive stress covered by the support structure resulting from the continuously applied load in the third fluid flow region gradually increases toward the third fluid flow region in each section along the support structure that becomes gradually more distal from the joint, causing elastic deformation of the support structure within the third fluid flow region, the graft according to item 92. (Item 96) The elastic deformation of the support structure within the third fluid flow region is reversible such that reversing the elastic deformation of the support structure within the third fluid flow region expands the diameter of the support structure within the third fluid flow region to a diameter less than the non-compressed diameter of the support structure, which is not under the compressive stress resulting from the continuously applied load within the third fluid flow region, the graft according to item 95. (Item 97) The elastic deformation of the support structure within the first fluid flow region due to the compressive stress resulting from the continuously applied load within the first fluid flow region is negligible at most, the graft according to item 92. (Item 98) The elastic deformation of the support structure along the central portion of the second fluid flow region due to the compressive stress resulting from the applied load within the second fluid flow region is negligible at most, the graft according to item 92. (Item 99) In combination with the biocompatible layer, prior to forming the wall, the support structure along the first fluid flow region has a constant effective inner diameter dimension, and the support structure along the third fluid flow region has an effective inner diameter dimension that gradually increases towards the third opening in each section along the support structure that becomes gradually more distal from the junction, the graft of item 92. (Item 100) In combination with the biocompatible layer, after forming the wall, the support structure has a substantially uniform effective inner diameter dimension with a constant effective inner diameter dimension along the first fluid flow region and a constrained effective inner diameter dimension along the third fluid flow region, the graft of item 99. (Item 101) The constrained effective inner diameter dimension is approximately equal to the constant effective inner diameter dimension, the graft of item 100. (Item 102) The compressive stress resulting from the continuously applied load maintains the support structure along the third fluid flow region at the constrained effective inner diameter dimension, the graft of item 101. (Item 103) A reaction force with a radially expanding force applied to the support structure along the third fluid flow region causes permanent deformation of the biocompatible layer, the graft of item 102. (Item 104) A reaction force with a radially expanding force applied to the support structure within the third fluid flow region causes a reduction in the compressive stress borne by the support structure, the graft of item 103. (Item 105) Following the application of a reaction force with a radially expanding force applied to the support structure within the third fluid flow region, the graft reconfigures to provide a permanently deformed biocompatible layer and a compressive stress borne by the support structure that is less than the compressive stress borne by the support structure prior to the application of the reaction force, the graft of item 104. (Item 106) Following the application of a reaction force with a radially expanding force applied to the support structure within the third fluid flow region, the graft reconfigures to provide a support structure that is subject to a reduced compressive stress that was previously greater by the support structure that covered it prior to the application of the reaction force, the graft according to item 105. (Item 107) The reaction force with a radially expanding force applied to the support structure within the third fluid flow region reconfigures the support structure along at least a portion of the support structure within the third fluid flow region from the constrained effective inner diameter dimension to an expanded effective inner diameter dimension that exceeds the constrained effective inner diameter dimension along the third fluid flow region, the graft according to item 106. (Item 108) The expanded effective inner diameter dimension exceeds the constrained effective inner diameter dimension by at least 1 mm along at least a portion of the support structure within the third fluid flow region, the graft according to item 107. (Item 109) The expanded effective inner diameter dimension of the support structure along the third fluid flow region, after reconfiguration, exceeds the constrained effective inner diameter dimension by at least 1 mm along the entire expandable portion of the radially supporting device structure within the third fluid flow region, the graft according to item 108. (Item 110) The expandable third fluid flow region comprises an elongate expandable third fluid flow region, the graft according to item 92. (Item 111) The elongate expandable third fluid flow region has a length that exceeds approximately five times the length of either the first fluid flow region or the second fluid flow region, the graft according to item 110. (Item 112) The length of the conduit between the junction and the outermost end of the third fluid flow region exceeds the combined length of the first fluid flow region and the second fluid flow region, the graft according to item 110. (Item 113) The graft of item 110, wherein the length of the conduit between the joint and the outermost end of the third fluid flow region is at least about 50 millimeters. (Item 114) The compressive stress covered by the support structure resulting from a continuous applied load within the elongate expandable third fluid flow region gradually decreases in one or more initial sections along the support structure before becoming constant across sections that are increasingly distal from the one or more initial sections. The graft of item 110. (Item 115) The compressive stress covered by the support structure resulting from a continuous applied load within the elongate expandable third fluid flow region gradually decreases in one or more initial sections along the support structure before becoming constant across sections that are increasingly distal from the one or more initial sections. The graft of item 110, wherein the elastic deformation of the support structure within the elongate expandable third fluid flow region is caused. (Item 116) The elastic deformation of the support structure within the elongate expandable third fluid flow region is reversible such that the diameter of the support structure within the elongate expandable third fluid flow region can be expanded to a diameter less than the uncompressed diameter of the support structure not under the compressive stress resulting from the continuous applied load within the elongate expandable third fluid flow region to reverse the elastic deformation of the support structure within the elongate expandable third fluid flow region. The graft of item 115. (Item 117) The elastic deformation of the support structure within the first and second fluid flow regions due to the compressive stress resulting from a continuous applied load within the first and second fluid flow regions is negligible at most. The graft of item 116. (Item 118) In combination with the biocompatible layer, prior to forming the wall, the support structure within the first vascular insertion region has a constant effective inner diameter dimension along the first fluid flow region and an effective inner diameter dimension along the third fluid flow region that gradually decreases in one or more initial sections and then becomes constant across sections that are increasingly distal from the one or more initial sections, the graft of item 117. (Item 119) In combination with the biocompatible layer, after forming the wall, the support structure within the first vascular insertion region comprises a constant effective inner diameter dimension along the first fluid flow region and a constrained effective inner diameter dimension along the elongated expandable third fluid flow region, the graft of item 118 having a substantially uniform effective inner diameter dimension. (Item 120) The constrained effective inner diameter dimension is approximately equal to the constant effective inner diameter dimension, the graft of item 119. (Item 121) The compressive stress resulting from the continuously applied load maintains the support structure along the elongated expandable third fluid flow region at the constrained effective inner diameter dimension, the graft of item 120. (Item 122) A reaction force comprising a radially expanding force applied to the support structure along the elongated expandable third fluid flow region causes permanent deformation of the biocompatible layer, the graft of item 121. (Item 123) A reaction force comprising a radially expanding force applied to the support structure within the elongated expandable third fluid flow region causes a reduction in the compressive stress borne by the support structure, the graft of item 122. (Item 124) Subsequent to the application of a reaction force comprising a radially expanding force applied to the support structure within the elongated expandable third fluid flow region, the graft reconfigures to provide a permanently deformed biocompatible layer and a compressive stress borne by the support structure that is less than the compressive stress borne by the support structure prior to the application of the reaction force, the graft of item 123. (Item 125) Following the application of a reaction force with a radially expanding force applied to the support structure within the elongate expandable third fluid flow region, the graft, prior to the application of the reaction force, reconfigures to provide a support structure that is subject to a reduced compressive stress that was previously greater and was covered by the support structure, as described in item 124. (Item 126) The reaction force with a radially expanding force applied to the support structure within the elongate expandable third fluid flow region reconfigures the support structure along at least a portion of the support structure within the elongate expandable third fluid flow region from the constrained effective inner diameter dimension to an expanded effective inner diameter dimension that exceeds the constrained effective inner diameter dimension along the elongate expandable third fluid flow region, as described in item 125. (Item 127) The expanded effective inner diameter dimension exceeds the constrained effective inner diameter dimension along at least a portion of the support structure within the elongate expandable third fluid flow region by at least 1 mm, as described in item 126. (Item 128) The expanded effective inner diameter dimension of the support structure along the elongate expandable third fluid flow region, after reconfiguration, exceeds the constrained effective inner diameter dimension by at least 1 mm along most of the support structure within the elongate expandable third fluid flow region, as described in item 127. (Item 129) A portion of the fourth fluid flow region is expandable, as described in item 92 or 110. (Item 130) The expandable portion of the support structure along the fourth fluid flow region is under a continuous compressive stress resulting from the continuous applied load caused by the biocompatible layer against the support structure, as described in item 129. (Item 131) The compressive stress covered by a part of the support structure resulting from the continuously applied load within the expandable fourth fluid flow region causes elastic deformation of the support structure within the expandable radial support device portion of the fourth fluid flow region, the graft according to item 130. (Item 132) The elastic deformation of the support structure within the expandable fourth fluid flow region is reversible such that reversing the elastic deformation expands the diameter of the support structure to a diameter less than the non-compressed diameter of the support structure, which is not under the compressive stress resulting from the continuously applied load within the expandable fourth fluid flow region, the graft according to item 131. (Item 133) The compressive stress resulting from the continuously applied load maintains the support structure along the expandable fourth fluid flow region at a constrained effective inner diameter dimension, the graft according to item 132. (Item 134) The reaction force with a radial expansion force applied to the support structure along the expandable fourth fluid flow region causes permanent deformation of the biocompatible layer, the graft according to item 133. (Item 135) The reaction force with a radial expansion force applied to the support structure within the expandable fourth fluid flow region causes a decrease in the compressive stress covered by the support structure, the graft according to item 134. (Item 136) Following the application of the reaction force with a radial expansion force applied to the support structure within the expandable fourth fluid flow region, the graft reconfigures to provide a permanently deformed biocompatible layer and a compressive stress covered by the support structure within the expandable fourth fluid flow region that is less than the compressive stress covered by the support structure prior to the application of the reaction force, the graft according to item 135. (Item 137) Following the application of the reaction force with a radial expansion force applied to the support structure within the expandable fourth fluid flow region, the graft reconfigures to provide a permanently deformed biocompatible layer, the graft according to item 136. (Item 138) Following application of a reaction force having a radially expanding force applied to the support structure within the expandable fourth fluid flow region, the graft reconfigures to provide a support structure that, prior to application of the reaction force, is subject to a reduced compressive stress that was previously covered by the support structure that was larger. The graft according to item 137. (Item 139) The reaction force having a radially expanding force applied to the support structure within the expandable fourth fluid flow region reconfigures the support structure along at least a portion of the support structure within the expandable fourth fluid flow region from the constrained effective inner diameter dimension to an expanded effective inner diameter dimension that exceeds the constrained effective inner diameter dimension along the expandable fourth fluid flow region. The graft according to item 138. (Item 140) The expanded effective inner diameter dimension exceeds the constrained effective inner diameter dimension by at least 1 mm along at least a portion of the expandable support structure within the fourth fluid flow region. The graft according to item 139. (Item 141) The expanded effective inner diameter dimension of the support structure along the fourth fluid flow region exceeds the constrained effective inner diameter dimension by at least 1 mm along the expandable support structure within the entire fourth fluid flow region after reconfiguration. The graft according to item 140. (Item 142) The fourth fluid flow region comprises an elongate expandable fourth fluid flow region. The graft according to item 92 or 110. (Item 143) The elongate expandable fourth fluid flow region has a length exceeding about 70 millimeters. The graft according to item 142. (Item 144) The compressive stress covered by the support structure resulting from a continuously applied load within the elongate expandable fourth fluid flow region gradually decreases in one or more initial sections along the support structure before becoming constant across each section that gradually becomes more distal from the fifth fluid flow region. The graft according to item 143. (Item 145) The compressive stress covered by the support structure resulting from the continuously applied load within the elongatable and expandable fourth fluid flow region becomes constant before traversing each section that gradually becomes more distal from the fifth fluid flow region, and gradually decreases in one or more initial sections along the support structure before becoming constant, causing elastic deformation of the support structure within the elongatable and expandable fourth fluid flow region, the graft according to Item 144. (Item 146) The elastic deformation of the support structure within the elongatable and expandable fourth fluid flow region is such that reversing the elastic deformation is reversible to expand the diameter of the support structure within the elongatable and expandable fourth fluid flow region to a diameter less than the uncompressed diameter of the support structure that is not under the compressive stress resulting from the continuously applied load within the elongatable and expandable fourth fluid flow region, the graft according to Item 145. (Item 147) In combination with the biocompatible layer, prior to forming the wall, the support structure within the elongatable and expandable fourth fluid flow region has an effective inner diameter dimension that gradually decreases in one or more initial sections along the support structure before becoming constant when traversing each section that gradually becomes more distal from the one or more initial sections, the graft according to Item 146. (Item 148) In combination with the biocompatible layer, after forming the wall, the support structure within the elongatable and expandable fourth fluid flow region has a constrained effective inner diameter dimension, the graft according to Item 147. (Item 149) The compressive stress resulting from the continuously applied load maintains the support structure along the elongatable and expandable fourth fluid flow region at the constrained effective inner diameter dimension, the graft according to Item 148. (Item 150) The reaction force with a radially expanding force applied to the support structure along the elongatable and expandable fourth fluid flow region causes permanent deformation of the biocompatible layer, the graft according to Item 149. (Item 151) The graft according to item 150, wherein a reaction force having a radially expanding force applied to the support structure within the elongated expandable fourth fluid flow region causes a reduction in the compressive stress borne by the support structure. (Item 152) Following the application of a reaction force having a radially expanding force applied to the support structure within the elongated expandable fourth fluid flow region, the graft reconfigures to provide a permanently deformed biocompatible layer and a compressive stress borne by the support structure that is less than the compressive stress borne by the support structure prior to the application of the reaction force, as described in item 151. (Item 153) Following the application of a reaction force having a radially expanding force applied to the support structure within the elongated expandable fourth fluid flow region, the graft reconfigures to provide a support structure that bears a reduced compressive stress that was previously greater and was borne by the support structure prior to the application of the reaction force, as described in item 152. (Item 154) The reaction force having a radially expanding force applied to the support structure within the elongated expandable fourth fluid flow region reconfigures the support structure along the elongated expandable fourth fluid flow region from the constrained effective inner diameter dimension to an expanded effective inner diameter dimension that exceeds the constrained effective inner diameter dimension along at least a portion of the support structure within the elongated expandable fourth fluid flow region, as described in item 153. (Item 155) The expanded effective inner diameter dimension exceeds the constrained effective inner diameter dimension by at least 1 mm along at least a portion of the support structure within the elongated expandable fourth fluid flow region, as described in item 154. (Item 156) The expanded effective inner diameter dimension of the support structure along the elongated expandable fourth fluid flow region, after reconfiguration, exceeds the constrained effective inner diameter dimension by at least 1 mm along most of the support structure within the elongated expandable fourth fluid flow region, as described in item 155. (Item 157) The longitudinal axis of the second fluid flow region intersects the longitudinal axis of the first fluid flow region at a non-parallel angle, the graft according to item 92. (Item 158) The non-parallel angle is approximately 25° to 45°, the graft according to item 157. (Item 159) The non-parallel angle is approximately 35°, the graft according to item 157. (Item 160) The second fluid flow region merges together at the junction with the first fluid flow region such that the first fluid flow region and the second fluid flow region are not perpendicular to each other, the graft according to item 92. (Item 161) The support structure is constructed from a shape memory alloy, the graft according to item 92. (Item 162) The support structure is constructed from nitinol, the graft according to item 92. (Item 163) The biocompatible layer comprises an expandable polymer, the graft according to item 92. (Item 164) The biocompatible layer includes ePTFE, the graft according to item 92. (Item 165) The biocompatible layer further comprises a biocompatible outer layer, the graft according to item 92. (Item 166) The biocompatible layer further comprises a biocompatible inner layer, the graft according to item 165. (Item 167) The biocompatible outer layer and the biocompatible inner layer enclose the support structure, the graft according to item 166. (Item 168) The biocompatible layer is not a surface-modified coating, the graft according to item 92. (Item 169) A graft, Comprising a conduit having a wall, the conduit At least one inflow opening at the inflow end of the body region, An outflow opening at the outflow end of the outflow region opposite to the at least one inflow opening, Comprising, Wherein the wall comprises a support structure and a biocompatible layer, and The support structure along the outflow region is under continuous compressive stress resulting from the continuous applied load caused by the biocompatible layer on the support structure, graft. (Item 170) The compressive stress resulting from the continuous applied load in the outflow region exceeds the compressive stress resulting from the continuous applied load in the body region, the graft according to item 169. (Item 171) The compressive stress covered by the support structure resulting from the continuous applied load in the outflow region gradually increases in each section along the support structure that gradually becomes more distal from the at least one inflow opening, the graft according to any one of item 169 or 170. (Item 172) The compressive stress covered by the support structure resulting from the continuous applied load in the outflow region causes elastic deformation of the support structure in the outflow region, the graft according to any one of item 169 - 171. (Item 173) The elastic deformation of the support structure in the outflow region gradually increases in each section along the support structure that gradually becomes more distal from the at least one inflow opening, the graft according to any one of item 169 - 172. (Item 174) The elastic deformation of the support structure in the outflow region is reversible, the graft according to any one of item 169 - 173. (Item 175) The compressive stress resulting from the continuous applied load in the body region does not elastically deform the support structure in the body region, the graft according to any one of item 169 - 174. (Item 176) The support structure, in combination with the biocompatible layer, has a plurality of effective outer diameter dimensions prior to forming the wall, and after forming the wall in combination with the biocompatible layer, has a substantially uniform effective outer diameter dimension, the graft according to any one of items 169 - 175. (Item 177) The graft according to item 176, wherein the plurality of effective outer diameter dimensions along the body region comprises a constant effective outer diameter dimension. (Item 178) The graft according to item 177, wherein the plurality of effective outer diameter dimensions along the outflow region comprises effective outer diameter dimensions that gradually increase in each section along the support structure that becomes gradually more distal from the at least one inflow opening. (Item 179) The graft according to item 178, wherein the substantially uniform effective outer diameter dimension comprises a constant effective outer diameter dimension along the body region and a constrained effective outer diameter dimension along the outflow region. (Item 180) The graft according to item 179, wherein the constrained effective outer diameter dimension is approximately equal to the constant effective outer diameter dimension. (Item 181) The graft according to item 179, wherein the compressive stress resulting from the continuously applied load maintains the support structure along the outflow region at the constrained effective outer diameter dimension. (Item 182) The graft according to item 179, comprising a reaction force with a radially expanding force applied to the support structure along the outflow region, which causes plastic deformation of the biocompatible layer. (Item 183) The graft according to item 179, wherein the reaction force with a radially expanding force applied to the support structure within the outflow region causes a decrease in the compressive stress borne by the support structure. (Item 184) Following application of a reaction force having a radially expanding force applied to the support structure within the outflow region, the graft reconfigures to provide a plastically deformed biocompatible layer and a compressive stress covered by the support structure that is less than the compressive stress covered by the support structure prior to application of the reaction force, as described in item 179. (Item 185) Following application of a reaction force having a radially expanding force applied to the support structure within the outflow region, the graft reconfigures to provide a plastically deformed biocompatible layer, as described in item 179. (Item 186) Following application of a reaction force having a radially expanding force applied to the support structure within the outflow region, the graft reconfigures such that the support structure bears a residual compressive stress if there was a continuous compressive stress covered by the support structure prior to application of the reaction force, as described in item 179. (Item 187) The reaction force having a radially expanding force applied to the support structure within the outflow region reconfigures the support structure along the outflow region to an expanded effective outer diameter dimension that exceeds the constrained effective outer diameter dimension along at least a portion of the support structure within the outflow region from the constrained effective outer diameter dimension, as described in item 179. (Item 188) The expanded effective outer diameter dimension exceeds the constrained effective outer diameter dimension by at least 1 mm along at least a portion of the support structure within the outflow region, as described in item 187. (Item 189) The expanded effective outer diameter dimension of the support structure along the outflow region, after reconfiguration, exceeds the constrained effective outer diameter dimension by at least 1 mm along the entire portion of the support structure within the outflow region, as described in item 187. (Item 190) The conduit further comprises a second inflow opening, as described in any of items 169 - 189. (Item 191) The longitudinal axis of the second inflow opening intersects the longitudinal axis of the at least one inflow opening at a non-parallel angle, the graft according to any one of items 169-190. (Item 192) The non-parallel angle comprises an angle of about 25° to 45°, the graft according to item 191. (Item 193) The non-parallel angle comprises an angle of about 35°, the graft according to item 191. (Item 194) The support structure is constructed from a shape memory alloy, the graft according to any one of items 169-193. (Item 195) The support structure is constructed from nitinol, the graft according to any one of items 169-194. (Item 196) The support structure has a zigzag wire shape, the graft according to any one of items 169-195. (Item 197) The biocompatible layer comprises an expandable polymer, the graft according to any one of items 169-196. (Item 198) The biocompatible layer comprises ePTFE, the graft according to any one of items 169-197. (Item 199) The biocompatible layer further comprises a biocompatible outer layer, the graft according to any one of items 169-198. (Item 200) The biocompatible layer further comprises a biocompatible inner layer, the graft according to any one of items 169-199. (Item 201) The biocompatible outer layer and the biocompatible inner layer enclose the support structure, the graft according to any one of items 169-200. (Item 202) The biocompatible layer is not a surface-modified coating, the graft according to any one of items 169-201. (Item 203) A vascular graft, A conduit having a wall, said conduit comprising: At least one inlet opening at an inlet end of a body region; An outlet opening at an outlet end of an outlet region opposite said at least one inlet opening; And Said wall comprising a support structure and a biocompatible layer; In combination with said biocompatible layer, prior to forming said wall, said support structure comprises a constant effective outer diameter dimension along said body region and an effective outer diameter dimension along said outlet region that gradually increases in each section along said support structure that is gradually more distal from said at least one inlet opening, said support structure comprising a plurality of effective outer diameter dimensions along its length; In combination with said biocompatible layer, after forming said wall, the support structure within said outlet region is under a compressive stress resulting from a continuously applied load caused by said biocompatible layer that maintains the support structure along said outlet region at a constrained effective outer diameter dimension that does not gradually increase in each section along said support structure that is gradually more distal from said at least one inlet opening; After application of a reaction force to the support structure within said outlet region, the support structure within said outlet region is reconfigured from said constrained effective outer diameter dimension to an expanded effective outer diameter dimension in which at least a portion thereof is at least 1 millimeter greater than said constrained effective outer diameter dimension, a vascular graft. (Item 204) A method of expanding an outlet end of a transplanted graft, comprising: (a) Providing a conduit having a wall, said conduit comprising: At least one inlet opening at an inlet end of a body region; An outlet opening at an outlet end of an outlet region opposite said at least one inlet opening; And Wherein said wall comprises a support structure and a biocompatible layer; In combination with the biocompatible layer, prior to forming the wall, the support structure comprises a plurality of effective outer diameter dimensions including a constant effective outer diameter dimension along the body region and an effective outer diameter dimension that gradually increases in each section along the support structure that is gradually more distal from the at least one inflow opening along the outflow region. In combination with the biocompatible layer, after forming the wall, the support structure within the outflow region is under a compressive stress resulting from a continuous applied load exerted by the biocompatible layer that maintains the support structure within the outflow region at a constrained effective outer diameter dimension that does not gradually increase in each section along the support structure that is gradually more distal from the at least one inflow opening. Identifying a transplanted graft comprising a conduit. (b) Applying a reaction force to the support structure within the outflow region, wherein applying the reaction force to the support structure within the outflow region reconfigures the support structure along the outflow region from the constrained effective outer diameter dimension to an expanded effective outer diameter dimension that exceeds the constrained effective outer diameter dimension, thereby expanding the outflow region of the transplanted graft. A method comprising. (Item 205) The method of item 204, wherein the outflow region comprises an outflow end that is crushed, stenotic, or has persistent intimal hyperplasia. (Item 206) The method according to any one of items 204 - 205, wherein the outflow end having the crushed, stenotic, or persistent intimal hyperplasia end impairs the patency of the vasculature into which the graft is transplanted. (Item 207) The method according to any one of items 204 - 206, wherein the step of applying the reaction force comprises expanding an expandable device within the outflow region of the transplanted graft. (Item 208) Prior to expanding the expandable device, the expandable device is advanced into the outflow region, the method according to any one of items 204 - 207. (Item 209) Prior to the advancement of the expandable device into the outflow region, the expandable device is percutaneously introduced into the implanted graft by the method according to any one of items 204 - 208. (Item 210) The method according to any one of items 204 - 209, wherein the expanded effective outer diameter dimension exceeds the constrained effective outer diameter dimension by at least 1 millimeter. (Item 211) The method according to any one of items 204 - 210, wherein the expanded effective outer diameter dimension exceeds the constrained effective outer diameter dimension by at least 1 millimeter along any portion of the support structure within the outflow region. (Item 212) A method for expanding the outflow region of an implanted graft, comprising: (a) A conduit having a wall, the conduit comprising: At least one inflow opening at an inflow end of a body region; and An outflow opening at an outflow end of an outflow region opposite the at least one inflow opening; and The wall comprises a support structure and a biocompatible layer, Wherein the support structure within the outflow region is under a compressive stress resulting from an applied load caused by the biocompatible layer; Providing an implanted graft comprising a conduit; (b) Reconfiguring the support structure along the outflow region from a constrained effective outer diameter dimension to an expanded effective outer diameter dimension that exceeds the constrained effective outer diameter dimension, thereby expanding the outflow end of the implanted graft, and applying a reaction force to the support structure within the outflow region. A method comprising the above steps. (Item 213) A method for fabricating a graft having an expandable outflow end, comprising: (a) Providing a support structure comprising at least one inlet opening at an inlet end of a body region and an outlet opening at an outlet end of an outlet region opposite the at least one inlet opening, the support structure having a plurality of effective outer diameter dimensions comprising a constant effective outer diameter dimension along the body region of the support structure and a gradually increasing effective outer diameter dimension along the outlet region of the support structure; (b) Combining the support structure with at least one biocompatible layer to form a conduit having a wall comprising the support structure and the at least one biocompatible layer; (c) Inserting a mandrel into the outlet opening proximal to the outlet end of the support structure; (d) Using compression winding to constrain the gradually increasing effective outer diameter dimension proximal to the outlet region of the support structure such that a continuous compressive stress results from a continuous applied load generated by the biocompatible layer that maintains the support structure along the outlet region at the constant effective outer diameter dimension and a uniformly constrained effective outer diameter dimension; (e) Sintering the at least one biocompatible layer in a section within the outlet region. A method comprising the above steps. (Item 214) A support structure comprising an expandable support having a design and configuration as shown in the drawings. (Item 215) A support structure comprising an expandable support having a design and configuration as shown in FIG. 8E. (Item 216) A support structure comprising an expandable support having a design and configuration as shown in FIG. 9D. (Item 217) A support structure comprising a body comprising a plurality of rings R1 to R n where n is an integer and each of the rings R1 to R n has a pattern as shown in FIG. 4; and a plurality of rings R n+1 、Rn+2 , R n+3 An extensible part comprising, where n is an integer, and each ring R n+1 , R n+2 , R n+3 has a pattern as shown in FIG. 4 and has length dimensions D1, D2, and D3 larger than the previous ring, and the extensible part, A support structure comprising. (Item 218) Each ring R1 to R n is connected to an adjacent ring via a plurality of struts each having a pattern as shown in FIG. 4, the support structure according to item 217. (Item 219) Ring R n+1 , R n+2 , R n+3 is each connected to an adjacent ring via a plurality of struts each having a pattern as shown in FIG. 4, the support structure according to any one of items 217 - 218. (Item 220) The plurality of rings R n+1 , R n+2 , R n+3 are configured to give a shape to the extensible part selected from the group consisting of the shapes shown in FIGS. 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J, 3K, 3L, 3M, 3N, 3O, and combinations and variations thereof, the support structure according to any one of items 217 - 219. (Item 221) A support structure, A body comprising a plurality of rings R3 to R n , where n is an integer, and each ring R3 to R n has a pattern as shown in FIG. 11, and the body, An expandable portion comprising rings R1 and R2, each ring having a pattern as shown in FIG. 11, ring R1 having a length dimension D2 that exceeds the length dimension D1 of R2, and ring R2 having a length dimension D1 that exceeds the length dimension of each ring from R3 to R n An expandable portion having a length dimension D1 that exceeds the length dimension of each ring from R3 to R, and A support structure comprising (Item 222) From each ring R3 to R n Is connected to an adjacent ring via a plurality of struts each having a pattern as shown in FIG. 11, the support structure according to item 221. (Item 223) Rings R1 and R2 are connected to adjacent rings via a plurality of struts each having a pattern as shown in FIG. 11, the support structure according to any of items 221-222. (Item 224) A support structure having an expandable outflow region, and a biocompatible layer that constrains the expandable outflow region under a continuous radially inward compressive stress that enables the outflow region to expand in response to the application of a radially outward reaction force to the outflow region, a graft. (Item 225) A method of expanding the outflow region of a transplanted graft, comprising: (a) A conduit having a wall, At least one inflow opening at the inflow end of the body region, and An outflow opening at the outflow end of the outflow region opposite the at least one inflow opening, Comprising Wherein the wall comprises a support structure and a biocompatible layer, The support structure within the outflow region is under a compressive stress resulting from the applied load generated by the biocompatible layer, Providing a transplanted graft comprising a conduit; (b) A step of reconstructing the support structure along the outflow region from a constrained effective outer diameter dimension to an expanded effective outer diameter dimension that exceeds the constrained effective outer diameter dimension, thereby applying a reaction force to expand the outflow end of the implanted graft to the support structure within the outflow region. A method comprising.

[0024] This patent or application contains at least one drawing created in color. Copies of this patent or patent application publication with color drawings will be provided by the Patent Office upon request and payment of the required fee.

[0025] These and other characteristics of the present invention will be more fully understood by referring to the following embodiments for carrying out the invention in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0026]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8A

Figure 8B

Figure 8C

Figure 8D

Figure 8E

Figure 8F

Figure 9A

Figure 9B

Figure 9C

Figure 9D

Figure 9E

Figure 9F

Figure 9G

Figure 9H

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15A

Figure 15B

Figure 15C

Figure 16A

Figure 16B

Figure 16C

Figure 17A

Figure 17B

Figure 17C

DETAILED DESCRIPTION

[0027] (DETAILED DESCRIPTION) The present invention is directed to various embodiments of a radially supported graft device and / or stent graft useful for various vascular access applications, including, but not limited to, facilitating vascular access in vascular bypass applications, facilitating the treatment of atherosclerosis, and facilitating arteriovenous access for dialysis treatment. In an exemplary embodiment, the device of the present invention has an expandable expanded end, a branching design, and / or a stent (i.e., a radially supporting structure) pattern configured to facilitate substantially sutureless and secure implantation of the device into the vascular access and the patient's vasculature. The present invention is described with reference to the figures, but it should be understood that many alternative forms can embody the present invention. Those skilled in the art will additionally understand different ways of modifying the disclosed parameters, such as size, shape, or type of element or material, in a manner that still maintains the spirit and scope of the present invention.

[0028] Referring now to the exemplary embodiments shown in FIGS. 1A through 17C, like parts are designated throughout by like reference numerals, and these figures illustrate exemplary embodiments of a vascular graft and methods of making and using the same according to the present invention. In particular, these embodiments show a vascular graft (e.g., for anastomosis) having an expandable outflow region, as well as methods of making and using the same, for restoring patency, for example, after implantation into a body passageway (e.g., a blood vessel).

[0029] A vascular graft 10 according to an exemplary embodiment of the present invention is illustrated in FIG. 1A. The vascular graft 10 is configured as a conduit 20 having a hollow body region 43 with an internal lumen 21 formed by a wall 30. The conduit 20 includes at least one inflow opening 32 at an inflow end 35 and an outflow opening 34 at an outflow end 36 of an outflow region 42 opposite the at least one inflow opening 32. The inflow end 35 and the outflow end 36 of the conduit 20 are in fluid communication with each other via the defined internal lumen 21 of the conduit 20 and extend between the at least one inflow opening 32 and the outflow opening 34. The wall 30 of the conduit 20 is formed by a support structure 40 and a biocompatible layer 50. The support structure 40 may be any device configured to maintain the patency of a blood vessel. An exemplary support structure 40 may include a stent. In one embodiment, the support structure 40 is an expandable structure and may be constructed from a shape memory alloy such as nitinol. In an exemplary embodiment, the biocompatible layer 50, which may be configured as a cover, sheath, or sleeve, may at least partially or completely cover the outer surface of the support structure 40. The support structure 40 may be separated from, adhered to, at least partially embedded within the material of the biocompatible layer 50, or any of the foregoing arrangements. The support structure 40 along the outflow region 42 is under a continuous compressive stress (S) resulting from the biocompatible layer 50 caused by a continuously applied load on the support structure 40. For example, the support structure 40 may elastically or springwise apply a continuously radially outwardly directed force to the biocompatible layer 50 such that the biocompatible layer 50 correspondingly applies a continuous compressive stress to the support structure 40.

[0030] Figures 2A, 2B, and 2C show views of the support structure 40 of the vascular graft 10 shown in Figure 1A, in combination with the biocompatible layer 50, prior to forming the wall 30 (Figure 2A), after combining the support structure 40 and the biocompatible layer 50 shown in Figure 2A to form the wall 30 (Figure 2B), and after expanding the outflow region 42 of the support structure 40 of the vascular graft 10 shown in Figure 2B (Figure 2C).

[0031] In Figure 2A, the support structure 40, in combination with the biocompatible layer 50 and prior to forming the wall 30 of the conduit 20, has a variable outer diameter along the length of the support structure 40. As shown, the support structure 40 has a constant effective outer diameter dimension D c along the body region 43, and an effective outer diameter dimension D that increases radially and outwardly toward the outflow opening 34 along at least a portion of the outflow region 42, giving the outflow region an "expanded" shape or appearance. inc This outwardly expanding configuration of the support structure 40 enables substantially sutureless attachment and retention of the stent graft 10 within the patient's vasculature. As shown in Figure 2A, depending on the coating of the support structure 40 with the biocompatible layer 50, the expanded outflow region 42 is contracted such that, as shown in Figure 2B, the conduit 20 is reshaped to have a constant effective outer diameter dimension D c along the lengths of the body region 43 and the outflow region 42. In an exemplary embodiment, the outflow region 42 is constructed from a shape memory alloy such as nitinol that is expandable from its constrained state to achieve and maintain the expanded configuration in response to the application of an expansion force such as balloon catheter expansion. This shape memory support structure 40 may be self-expanding, but due to the compressive stress applied by the biocompatible layer 50, it cannot assume its expanded state without balloon expansion. 2C shows the expanded effective outer diameter dimension D exp of the support structure 40 after an external expansion force has been applied to the outflow region 42 of the support structure 40 in Figure 2B.

[0032] Figures 3A - 3O show various exemplary embodiments of the outflow region 42 of the support structure 40 and depict various expanded configurations. These illustrations represent the wireframe profile of the support structure 40 without depicting its strut pattern. One of ordinary skill in the art can recognize that several different strut patterns can be utilized and that all such patterns are considered to be within the scope of the depicted profiles. With respect to FIGS. 3K - 3O, one of ordinary skill in the art can further recognize that the diameter of each support structure section along the support structure 40 within the outflow region 42 can vary depending on the particular implementation. In the exemplary embodiments of FIGS. 3K and 3M, each of the support structure sections generally forms a conduit having a stepped increment where the diameter of the support structure section increases as it approaches the outflow opening 34 and is constructed from a single zigzag ring (as described below). In another exemplary embodiment, the support structure 40 appears such that a portion of the outflow region 42, i.e., the portion between the proximal and distal ends of the outflow region 42, has a substantially uniform linear change in diameter (e.g., FIG. 3A), or alternatively, a curved change in diameter (e.g., FIGS. 3F and 3I) rather than a stepped change in diameter and may include a plurality of these stepped increments at sufficiently frequent intervals. In yet another exemplary embodiment, the increments can occur such that the effective outer diameter does not change along at least one section along the support structure 40 within the outflow region 42 (e.g., FIGS. 3B, 3C, 3G, 3J, 3L, 3M, 3N, and 3O). In one exemplary embodiment, the increments can occur so as to combine any of the foregoing configurations (e.g., FIGS. 3L, 3N). One of ordinary skill in the art can readily envision other suitable expanded configurations that can be considered to be within the scope of the present invention.

[0033] Referring now to FIG. 4, a wireframe design forming an exemplary support structure 40 structure of the outflow region 42 is illustrated. FIG. 4 shows a properly scaled illustration of the support structure 40 and shows the precise relative proportions of the support structure pattern depicted therein in a flat orientation. As shown, the support structure 40 is a series of interconnected rings (e.g., R1, R n , R n+1 , R n+2 , R n+3, where n = representative integer value), each having a substantially zigzag shape with a series of peaks and valleys. Once the flattened wireframe is wound into a three-dimensional cylindrical configuration, the peak or top of each ring faces directly and aligns with the corresponding valley of the adjacent ring, and vice versa. This peak and valley arrangement exists throughout the length of the support structure 40, creating a flexible structure that allows the stent 20 to bend and change orientation when implanted. FIG. 4 illustrates an exemplary strut or stent pattern of the support structure 40.

[0034] In the embodiment shown in FIG. 4, the support structure 40 within the outflow region 42 has an effective outer diameter dimension D that increases gradually in each section (D, D1, D2, D3) along the support structure 40, in each successively more distal portion or section extending from at least one inflow opening 32 to at least one outflow opening 34. inc In this non-limiting example, the support structure 40 can be constructed from a series of interconnected rings (e.g., R1, R n , R n+1 , R n+2 , R n+3 , where n = representative integer value), each having a substantially zigzag shape. As an example, in one embodiment, the rings R1 and R n of the support structure 40 are located within the proximal body region 43 of the outflow region 42, while the rings R3, R4, and R5 are located within the outflow region 42, and R5 forms the edge of the outflow opening 34. The rings R1 and R n of the body region 43 may have the same size and dimension D. On the other hand, the rings within the body region 43 generally have the same size and dimension, and the rings R3, R4, and R5 have successively increasing widths (i.e., the lengths of the peaks and valleys) D1, D2, and D3 of the rings. The effective outer diameter dimension of the support structure 40 increases in each ring section R as the width of each ring section D increases. For example, the width D1 of the ring section R3 is greater than the width D of the ring section R n , thereby causing the ring section R nIn contrast, the effective outer diameter dimension of the support structure 40 in the ring section R3 is increased, and the width D2 of the ring section R4 is greater than the width D1 of the ring section R3, whereby the effective outer diameter dimension of the support structure 40 in the ring section R4 is increased with respect to the ring section R3, and the width D3 of the ring section R5 is greater than the width D2 of the ring section R4, whereby the effective outer diameter dimension of the support structure 40 in the ring section R5 is increased. The effective outer diameter dimension of the support structure 40 in the outflow region 42 thus gradually increases in each section along the support structure 40 that becomes gradually more distal from at least one inflow opening 32. Only three ring sections R n+1 、R n+2 、and R n+3 are shown, but it should be understood that the outflow region 42 of the support structure 40 can comprise more (e.g., 4, 5, 6, etc.) or fewer (e.g., 2) ring sections R depending on the particular application, as would be recognized by those skilled in the art

[0035] As shown in the embodiment (described above) illustrated in FIGS. 3A - 3O, any particular section R (R n+1 、R n+2 、R n+3 ) having a width D (D1, D2, D3) can have a constant effective outer diameter dimension D c . In such an embodiment, the support structure 40 expands at each location within the outflow region 42 where the effective outer diameter dimension increases and does not expand at each location where the effective outer diameter dimension remains constant. In some embodiments, the support structure 40 first expands, for example, in section R n due to the width D1 that gradually becomes larger with respect to the width D of R n+1 , and then, for example, in sections R n+1 and R n+2Due to a constant effective outer diameter dimension resulting from the support structure in [reference to a specific context], it becomes horizontal at the outflow end 36 (i.e., Figures 3B - 3C). One skilled in the art can readily recognize that the length of the horizontal section of the initial expansion or outflow region 42 can vary as desired by increasing the widths D1, or D2 and D3 respectively. In certain embodiments (previously described) illustrated in Figures 3A through 3O, any specific section R (R n+1 、R n+2 、R n+3 ) having a width D (D1, D2, D3) can have an effective outer diameter dimension that increases at a greater rate than the previous section R. In certain embodiments (previously described) illustrated in Figures 3A through 3O, any specific section R (R n+1 、R n+2 、R n+3 ) having a width D (D1, D2, D3) can have an effective outer diameter dimension that increases at a lesser rate than the previous section R. The expanded outflow region 42 can be configured to modify the size and / or shape of its expanded appearance as long as the effective outer diameter dimension of the support structure 40 prior to forming the wall 30 in combination with the biocompatible layer 50 increases along at least a portion of the outflow region 42, which should be understood by those skilled in the art. One skilled in the art should recognize that the expanding appearance (e.g., size, shape, or angle) within the outflow region 42 depends in part on the widths D1, D2, D3 of each respective ring section R n+1 、R n+2 、R n+3 .

[0036] Various dimensions D (e.g., D, D1, D2, D3) are contemplated for the ring sections R (e.g., R1, R n 、R n+1 、R n+2 、R n+3 ). Table 1 below provides a non - limiting example of dimensions for manufacturing the support structure 40 having an effective outer diameter dimension D inc that gradually increases within the outflow region 42.

[0037]

Table 1

[0038] In the exemplary embodiments shown in FIGS. 8A - 8G, the outlet region 42 has the same expandable configuration as shown in FIGS. 1A - 2C and generally as discussed above. The inlet region 44 of this alternative stent graft 10 may have a pre - processed and pre - extended expanded configuration prior to implantation, as shown in FIGS. 8A - 8G. In the various figures of this stent graft embodiment, the support structure 40 has a pre - processed and pre - extended outwardly expanding inlet region 44 along the inflow region 44 to maintain or improve the graft's patency. In these examples, the expanded shape or appearance is oriented in a direction opposite to the expanded shape or appearance at the outflow end 36. The pre - processed and pre - extended expanded configuration of the inflow region 44 facilitates friction - fit attachment and positioning within the vasculature.

[0039] FIG. 8A shows a side view of the straight vascular graft shown in FIG. 1A, illustrating the expanded configuration of the inlet region 44 of the support structure 40 prior to forming the wall 30 in combination with the biocompatible layer 50. FIG. 8B shows a schematic view of the straight vascular graft shown in FIG. 1A, illustrating the pre - processed and pre - extended expanded configuration of the support structure 40 along the inlet region 44 and the expandable outflow region 42 after combining the support structure 40 and the biocompatible layer 50 shown in FIG. 8A to form the wall 30. FIG. 8B shows the vascular graft after the inlet region 44 has been expanded. FIG. 8C shows a schematic view of the straight vascular graft shown in FIG. 1A, illustrating the expanded effective outer diameter dimension D exp thereof along the outflow region 42. FIG. 8D shows a side wireframe view of the support structure 40 shown in FIGS. 8A and 8D. FIG. 8E is a photograph showing the actual structure of the support structure 40 shown in FIG. 8A.

[0040] In particular, referring to FIG. 8E, the pre - processed and pre - expanded expanded shape or appearance of the inlet region 44 is such that the ring sections R1 and R2 of the support structure 40 have different widths D2, D1 respectively, and from the ring section R3 to R nIt is demonstrated that it can be achieved by a similar design methodology as described in FIG. 4 with a width D different from (n = integer). The ring sections R (e.g., from R1, R2, R3 to R n , where n = integer) with different widths D (e.g., D2, D1, D) provide an expanded appearance to the support structure 40 along the outflow region 42, imparting an effective outer diameter dimension D inc .

[0041] The outflow region 42 of the support structure 40 may be configured in the same manner as described above and shown in FIG. 4B. FIG. 8F shows a schematic view of the support structure 40 useful in the inflow region 44 by way of an exemplary structure. This structure can be utilized for at least two purposes. In a first embodiment, the expanded inflow region 44 is pre-processed prior to implantation to generate a pre-expanded and expanded configuration. In another embodiment, the pre-expanded and expanded configuration is separate from the biocompatible layer 50 but potentially constructed from the same base material as the biocompatible layer 50, providing a locally increased inner diameter for receiving a lumen (e.g., as in a socket), thus providing a space for receiving the lumen. For example, an extending lumen 51 having a wall thickness thicker than that of layer 50 may be inserted into a socket constructed such that the inner lumen surface of the extending lumen 51 is substantially in the same plane as or at least of the same approximate diameter as the inner lumen surface of the conduit body portion 43.

[0042] FIG. 8F shows a scaled illustration of the support structure 40 showing the precise relative proportions of the support structure pattern depicted therein. Each ring forming the conduit body portion 43 comprises a series of hills and valleys best shown as R n and R3 in FIG. 8F. The respective hills or crests of these rings face directly and are aligned with the corresponding valleys of the adjacent rings, and the struts connecting the adjacent rings incorporate flexibility into the graft and facilitate in-situ bending. The proximal inflow region 35 of the support structure 40 includes a plurality of rings where the hills or crests of ring R2 face the hills and crests of the adjacent ring R1 while the valleys of ring R2 face directly and are aligned with the valleys of the adjacent ring R1, providing additional stiffness in the inflow region 35.

[0043] As shown in FIG. 8F, the ring sections R1 and R2, which are located proximal to the inflow end 35 of the inflow region 44 of the support structure 40, are each from the ring section R3 located within the body region 43 of the support structure 40 to R n (n is an integer) having widths D2 and D1 wider than that. Providing the ring section R2 with a width D1 larger than the width D of the ring section R3 expands the wall 30 adjacent to the ring section R2 outward as illustrated by the angled R2 section shown in FIG. 8D. The effective outer diameter dimension D of the inflow region 44 shown in this embodiment inc consists of the ring section R1, which has a constant effective outer diameter dimension along its width D2, as illustrated by a line extending along the longitudinal width of the ring section R1 shown in FIG. 8D. However, it should be understood by those skilled in the art that the proximal support structure 40 of the inflow region 44 can be formed in any desired manner that maximizes the patency of the inflow region while the vascular graft 10 is being implanted into the body lumen.

[0044] Referring now to FIGS. 2B and 8B, schematic views of embodiments of the vascular graft 10 shown in FIGS. 1A and 8A are shown, depicting the substantially uniform effective outer diameter dimension of the support structure 40 after combining the support structure 40 and the biocompatible layer 50 shown in FIGS. 2A and 8A to form the wall 30. The application of the biocompatible layer 50 to the outer surface of the support structure 40 to form the wall 30 places the support structure 40 within the outflow region 42 under a continuous compressive radial stress S (e.g., a radial compressive stress) resulting from the continuous applied load to the support structure 40 by compressing the biocompatible layer 50 against the support structure 40. Generally, the compressive stress S resulting from the continuous applied load within the outflow region 42 exceeds the compressive stress S0 resulting from the applied load within the body region 43. One of ordinary skill in the art can recognize that the compressive stress S resulting from the continuous radial applied load within the outflow region 42 generally varies along the length of the outflow region 42 as the effective outer diameter of the support structure 40 within the outflow region 42 changes. As shown in FIGS. 2B and 8B, for example, the compressive stress S covered by the support structure 40 resulting from the continuous applied load within the outflow region 42 gradually increases along the length of the support structure 40 as it approaches the outflow opening 34, i.e., the compressive stress S is greater in each section along the support structure 40 that is gradually more distal from at least one inflow opening 32 at the inflow end 35. In this embodiment, the compressive stress S is minimum S min at the proximal area of the outflow region 42, and increases as the effective outer diameter of the support structure 40 increases toward the maximum compressive stress S max at the proximal of the outflow end 36 (prior to combining with the biocompatible layer 50 to form the wall 30).

[0045] The compressive stress S causes elastic deformation of the support structure 40 within the outflow region 42. As understood by one of ordinary skill in the art, the degree of elastic deformation is a function of the compressive stress S resulting from the applied load caused by the biocompatible layer 50. In the embodiments shown in FIGS. 2B and 8B, the elastic deformation of the support structure 40 within the outflow region 42 is from the minimum compressive stress S min to the maximum compressive stress S maxAs illustrated by the increasing compressive stress, it gradually increases in each section along the support structure 40 that becomes gradually more distal from at least one inflow opening 32.

[0046] In contrast to the deformation that induces the compressive stress S along the outflow region 42, the compressive stress S0 resulting from the applied load by the biocompatible layer 50 in the inflow distal end 35 and the body region 43 causes only a negligible elastic deformation of the support structure 40 along the body region 43. For clarity, the negligible compressive stress S0 covered by the support structure 40 in the body region 43 resulting from the applied load caused by the biocompatible layer 50 on the support structure 40 is the compressive stress S (S min from S max ) that should be understood by those skilled in the art to be negligible compared to the amount. As used herein, the negligible compressive stress S0, as understood by those skilled in the art, does not accompany or is not associated with a change in the effective outer diameter of the portion or region of the support structure 40 that is subject to the compressive stress S, or only a very small amount of change in the effective outer diameter is accompanied or associated with it, and refers to the amount of compressive stress. In combination with the biocompatible layer 50, after forming the wall 30, in contrast to the negligible compressive stress S0 covered by the support structure 40 in the body region 43, the support structure 40 in the outflow region 42, in combination with the biocompatible layer 50, generally experiences a substantial amount of compressive stress that changes as the effective outer diameter dimension of the support structure 40 changes prior to forming the wall 30 in combination with the biocompatible layer 50. As used herein, "substantial compressive stress" and "continuous compressive stress" are used herein in the same meaning, as understood by those skilled in the art, and refer to the amount of compressive stress that accompanies or is associated with a change in the effective outer diameter of the portion or region of the support structure 40 that is subject to the compressive stress S in the radial direction.

[0047] The combination of the gradually increasing elastic deformation of the support structure 40 along the outflow region 42 and the absence of elastic deformation of the support structure 40 along the body region 43 imparts a uniform effective outer diameter dimension to the conduit 20, as shown in FIGS. 2B and 8B. This effective outer diameter dimension includes a constant effective outer diameter dimension D c along the body region 43 and a constrained effective outer diameter dimension D con along the outflow region 42. As used herein, "constrained", in combination with "effective outer diameter dimension", refers to the effective outer diameter dimension of the support structure 40 along the outflow region 42 in the absence of the compressive stress S prior to forming the wall 30 by combining the support structure 40 and the biocompatible layer 50, as opposed to the effective outer diameter dimension of the support structure 40 along the outflow region 42 under the compressive stress S. The constrained effective outer diameter dimension D con is approximately equal to the constant effective outer diameter dimension D c . Notably, the compressive stress S resulting from the continuously applied load maintains the support structure 40 along the outflow region 42 at the constrained effective outer diameter dimension D con .

[0048] The elastic deformation of the support structure 40 along the outflow region 42 is reversible. The range within which the elastic deformation of the support structure 40 along the outflow region 42 can be reversible depends on various factors, as understood by those skilled in the art, including the length D (e.g., D1, D2, D3) of each ring section R (e.g., R n+1 , R n+2 , R n+3 ) and the amount of reaction force applied to the support structure 40 within the outflow region 42. In this regard, a reaction force with a radially expanding force applied to the support structure 40 within the outflow region 42 causes plastic deformation of the biocompatible layer 50. Such a reaction force results in a decrease in the compressive stress S borne by the support structure 40. In other words, as the reaction force increases the plastic deformation of the biocompatible layer 50, the compressive stress S borne by the support structure 40 decreases, reversing the plastic deformation of the support structure 40.

[0049] Focusing now on FIGS. 2C and 8C, a schematic view of an embodiment of the vascular graft 10 shown in FIGS. 1A and 8A is shown, and the expanded effective outer diameter dimension D of the support structure 40 of the vascular graft shown in FIGS. 2B and 8B after expanding the outflow region 42 of the support structure 40 exp is depicted. As described above, the expanded effective outer diameter dimension D of the support structure 40 along the outflow region 42 exp results from the application of a reaction force with a radial expansion force. The present invention contemplates the use of any suitable means for applying such a radial expansion force, for example, by advancing a radially expandable device (e.g., balloon catheter 98) along the inner lumen of the conduit 20 from at least one inflow opening 32 toward the outflow opening 34 and expanding the radially expandable element. Other suitable means for applying such a radial expansion force will be apparent to those skilled in the art.

[0050] Those skilled in the art will further recognize that the present invention contemplates the use of any amount of reaction force with a radial expansion force that can overcome the continuous applied load contributed by the biocompatible layer 50 and thus enable the expansion of the outflow region 42. Preferably, the amount of reaction force with a radial expansion force used is an amount that results in non-traumatic expansion of the outflow region 42 within the body lumen. Exemplary ranges of such reaction forces may be apparent to those skilled in the art. However, for clarity, as exemplary ranges of reaction forces that may result in non-traumatic expansion of the outflow region 42 in vivo or in situ, those resulting from using a semi-compliant balloon that does not exceed 2.5 mm (more preferably, does not exceed 2.0 mm) across the effective outer diameter dimension of the outflow region 42 are mentioned.

[0051] Following the application of a reaction force with a radially expanding force applied to the support structure 40 within the outflow region 42, the graft reconfigures to provide a plastically deformed biocompatible layer 50. In some instances, following the application of the reaction force, the vascular graft 10 reconfigures to provide a plastically deformed biocompatible layer 50 and a compressive stress S that is less than the compressive stress S covered by the support structure 40 and covered by the support structure 40 prior to the application of the reaction force. In some instances, following the application of the reaction force, the graft reconfigures such that if there was a previously continuous compressive stress S (e.g., a substantial compressive stress) covered by the support structure 40 prior to the application of the reaction force, the support structure 40 is covered by a residual compressive stress S. As used herein, "residual compressive stress" means the amount of compressive stress S that remains partially as a result of the recoil associated with the plastic deformation of the biocompatible layer 50 in response to the application of a reaction force with a radially expanding force. One of ordinary skill in the art will recognize that the amount of such residual compressive stress depends on various factors including, for example, the magnitude of the radially expanding force and the amount of compressive stress S covered by the support structure 40 resulting from the continuous applied load 50 caused by the biocompatible layer on the support structure 40 prior to the application of the reaction force.

[0052] Still referring to FIGS. 2C and 8C, a reaction force with a radially expanding force applied to the support structure 40 within the outflow region 42 causes the constrained effective outer diameter dimension D shown in FIGS. 2B and 8B con to an expanded effective outer diameter dimension D shown in FIGS. 2C and 8C that exceeds the constrained effective outer diameter dimension D along at least a portion of the support structure 40 within the outflow region 42 con to reconfigure the support structure 40 within the outflow region 42 is apparent. In one embodiment, the change in diameter between the constrained effective outer diameter dimension D exp and the expanded effective outer diameter dimension D con is from about 0.5 mm to about 2.5 mm or from about 1 mm to about 2 mm, and further, from 1 mm to 1.5 mm. According to another exemplary embodiment, the expanded effective outer diameter dimension D exp is the constrained effective outer diameter dimension D along at least a portion of the support structure 40 within the outflow region 42 exp conexceeds at least 1 mm. Of course, the expanded effective outer diameter dimension D exp is, as will be understood by those skilled in the art, at least along a portion of the support structure 40 into the outflow region 42, depending on various factors such as the magnitude and duration of the radial expansion force and the length D (e.g., D1, D2, D3, etc.) or amount of the ring segments R (e.g., R n+1 , R n+2、 R n+3 etc.), the constrained effective outer diameter dimension D con is at least 1.10 mm, at least 1.20 mm, at least 1.30 mm, at least 1.40 mm, at least 1.50 mm, at least 1.60 mm, at least 1.70 mm, at least 1.80 mm, at least 1.90 mm, at least 2.0 mm, at least 2.10 mm, at least 2.20 mm, at least 2.30 mm, at least 2.40 mm, at least 2.50 mm, at least 2.60 mm, at least 2.70 mm, at least 2.80 mm, at least 2.90 mm, at least 3.0 mm, at least 3.10 mm, at least 3.20 mm, at least 3.30 mm, at least 3.40 mm, at least 3.50 mm, at least 3.60 mm, at least 3.70 mm, at least 3.80 mm, at least 3.90 mm, at least 4.0 mm, at least 4.10 mm, at least 4.20 mm, at least 4.30 mm, at least 4.40 mm, at least 4.50 mm, at least 4.60 mm, at least 4.70 mm, at least 4.80 mm, at least 4.90 mm, or 5.0 mm or greater. According to another exemplary embodiment, the expanded effective outer diameter dimension D exp of the support structure 40 along the outflow region 42, after being reconfigured, exceeds the constrained effective outer diameter dimension D con by at least 1.0 mm over the entire portion of the support structure 40 within the outflow region 42. In one exemplary embodiment, the expanded effective outer diameter dimension D exp is, as will be understood by those skilled in the art, along the entire portion of the support structure 40 within the outflow region 42, the constrained effective outer diameter dimension D conAt least 1.10 mm, at least 1.20 mm, at least 1.30 mm, at least 1.40 mm, at least 1.50 mm, at least 1.60 mm, at least 1.70 mm, at least 1.80 mm, at least 1.90 mm, at least 2.0 mm, at least 2.10 mm, at least 2.20 mm, at least 2.30 mm, at least 2.40 mm, at least 2.50 mm, at least 2.60 mm, at least 2.70 mm, at least 2.80 mm, at least 2.90 mm, at least 3.0 mm, at least 3.10 mm, at least 3.20 mm, at least 3.30 mm, at least 3.40 mm, at least 3.50 mm, at least 3.60 mm, at least 3.70 mm, at least 3.80 mm, at least 3.90 mm, at least 4.0 mm, at least 4.10 mm, at least 4.20 mm, at least 4.30 mm, at least 4.40 mm, at least 4.50 mm, at least 4.60 mm, at least 4.70 mm, at least 4.80 mm, at least 4.90 mm, or 5.0 mm or greater can be significantly larger.

[0053] The support structure 40 is such that the support structure 40 within the outflow region 42 has a constrained effective outer diameter dimension D con from, to an expanded effective outer diameter dimension D exp and can be constructed from any material that allows it to reconfigure. According to one exemplary embodiment, the support structure 40 is constructed from a shape memory alloy. Exemplary shape memory alloys can be formed from combinations of metals including, but not limited to, aluminum, cobalt, chromium, copper, gold, iron, nickel, platinum, tantalum, and titanium. According to one exemplary embodiment, the support structure 40 is constructed from nitinol. Other shape memory alloys or other materials that can be used to construct the support structure 40 will be apparent to those skilled in the art.

[0054] One skilled in the art can recognize that the support structure 40 can be constructed using larger or smaller expandable portions. One skilled in the art can also recognize that the same methodology described above with respect to FIG. 3, which enables the outflow region 42 to be expandable, can be applied to make other portions of the support structure 40 (e.g., the body region) expandable.

[0055] The biocompatible layer 50 can be constructed from any biocompatible material. The material may further be substantially impermeable to fluids in some embodiments. The material combines the support structure 40 and the biocompatible layer 50 to maintain the constrained effective outer diameter dimension D of the support structure 40 along the outflow region 42 after forming the wall 30. con To maintain this, it is possible to create a continuous applied load such that the support structure 40 is placed under a sufficient continuous compressive stress (e.g., a substantial compressive stress as defined herein). According to an exemplary embodiment, the biocompatible layer 50 comprises an expandable polymer. According to an exemplary embodiment, the biocompatible layer 50 comprises expanded polytetrafluoroethylene (ePTFE).

[0056] Generally, as shown in FIGS. 2B - 2C and 8B - 8C, the biocompatible layer 50 extends from the inflow end 35 to the outflow end 36 at least along the entire longitudinal length of the support structure 40. As understood by one skilled in the art, the biocompatible layer 50 may extend at least partially beyond or before the inflow end 35 and the outflow end 36 according to acceptable manufacturing specifications. According to one exemplary embodiment, the biocompatible layer 50 extends beyond the edges of the inflow end 35 and the outflow end 36 and can wrap around at least a portion of the inner surface of the support structure 40 in the form of a cuff.

[0057] Referring to FIGS. 5A, 5B, 5C, and 5D, exemplary cross-sections of the vascular graft 10 shown in FIGS. 1A and 8A are shown, depicting various ways in which the biocompatible layer 50 can be constructed. As can be seen from the exemplary embodiments of FIGS. 5A and 5C, the biocompatible layer 50 can comprise a biocompatible outer layer 54 and a separate biocompatible inner layer 55 spaced therefrom such that the outer layer 54 and the inner layer 55 are positioned on opposite sides of the support structure 40. As shown in FIGS. 5A and 5B, the biocompatible outer layer 54 and the biocompatible inner layer 55 can be configured as separate layers of the same substrate continuously wound around the ends of the support structure 40, or alternatively, as two separate substrates (i.e., non-continuous) positioned on opposite sides of the support structure 40. In this example, either the biocompatible outer layer 54 or the biocompatible inner layer 55 can extend at least partially beyond the edges of the inflow end 35 and the outflow end 36, wrap around them, forming a cuff, which can, for example, minimize damage to the surrounding tissue during deployment of the vascular graft 10. The circular portion of FIG. 5A is represented as FIG. 5B, showing an exploded view of a portion of the biocompatible layer 50, demonstrating how the biocompatible outer layer 54 and the biocompatible inner layer 55 can conform to each other and the support structure 40 as a result of methods (which are known to those skilled in the art) by which these layers can be applied, heated, sintered, or otherwise adhered onto or to the support structure 40. As shown in the exemplary embodiment in FIG. 5B, the biocompatible layer 50 can comprise the biocompatible outer layer 54 without the biocompatible inner layer 55. However, one skilled in the art may recognize that the biocompatible inner layer can serve to reduce the likelihood of stenosis or occlusion within the conduit 20 of the vascular graft 10 or to modify the fluid impermeability of the wall 30. FIGS. 5A-5D show exemplary embodiments of the vascular graft 10 in which the biocompatible layer 50 encloses the support structure 40 using the biocompatible outer layer 54 and the biocompatible inner layer 55. In this example, the biocompatible outer layer 54 and the biocompatible inner layer 55 can be configured to enclose the support structure 40.All known methods and structures related to the application or use of biocompatible layers such as those described herein are expected to be used in combination with the present invention, and the formation of the layers of the support structure is not limited by the specific illustrative embodiments provided herein.

[0058] In an exemplary embodiment, the biocompatible layer 50 is configured as a sheath, sleeve, or other covering that binds and applies a compressive force to the support structure 40. In an exemplary embodiment, the biocompatible layer 50, particularly the biocompatible outer layer 54, is adhesively bonded to the outer surface of the support structure 40 to form a cover that shrinks and is continuous over the support structure 40. The cover may be constructed of any suitable biocompatible material, particularly ePTFE, that is treated to apply a compressive force to the support structure 40. In an exemplary embodiment, the biocompatible layer 50, including the biocompatible outer layer 54 and / or the biocompatible inner layer 55, forms a blood-compatible cover that is configured and / or adapted to engage tissue and / or blood. It should be understood that the biocompatible layer 50 described herein is distinct from a mere surface modification coating, such as a hydrophilic coating, that is conventionally applied to a medical device for the purpose of delivering a therapeutic agent or changing the surface properties of the medical device. It is contemplated that such surface modification coatings, such as coatings containing biological oils or fats as described in U.S. Patent No. 8,124,127, which is incorporated herein by reference in its entirety, can be used to coat at least a portion of the surface of the support structure 40 or the biocompatible outer 54 and inner 55 layers for reasons that will be apparent to those skilled in the art. For example, it may be desirable to coat at least a portion of the inner surface of the support structure 40 or the biocompatible inner layer 55 with a cured fish oil coating containing an anticoagulant therapeutic agent to prevent or minimize occlusion of the implanted graft.

[0059] Referring now to FIG. 1B, an alternative embodiment of the vascular graft 10' is shown. The embodiment shown in FIG. 1A depicts a straight vascular graft 10, while the vascular graft 10' of FIG. 1B may be designed to include a second inflow opening 33 and provide a bifurcated or generally T-shaped vascular graft 10', as depicted in the embodiment shown in FIG. 1B. It should be understood that any description given with respect to components common to both grafts 10 and 10' (i.e., those components identified by the same reference numerals) is generally applicable to both embodiments, unless otherwise indicated. As shown in FIG. 1B, the longitudinal axis of the second inflow opening 33 intersects the longitudinal axis of at least one inflow opening 32 at a non-parallel angle. As used herein, "non-parallel angle" means an angle (e.g., greater than 0°) at which the longitudinal axis of at least one inflow opening 32 is not parallel to the longitudinal axis of the second inflow opening 33. The non-parallel angle can be any non-parallel angle greater than 0° and less than 180°, depending on the particular arrangement required for graft implantation. Preferably, the non-parallel angle at which the longitudinal axis of the second inflow opening 33 intersects the longitudinal axis of at least one inflow opening 32 is from about 25° to about 45°. According to one exemplary embodiment, the non-parallel angle at which the longitudinal axis of the second inflow opening 33 intersects the longitudinal axis of at least one inflow opening 32 is about 35°.

[0060] FIGS. 6A, 6B, and 6C show various views of an embodiment of the support structure 40 of the bifurcated vascular graft 110 structure shown in FIG. 1B, in combination with the biocompatible layer 50, prior to forming the wall 30 (FIG. 6A), after combining the support structure 40 shown in FIG. 6A with the biocompatible layer 50 to form the wall 30 (FIG. 6B), and after expanding the outflow region 42 of the support structure 40 coated with the biocompatible layer 50 of the vascular graft 110 shown in FIG. 6B (FIG. 6C). Those skilled in the art will appreciate that the description of the structure, function, and components of the straight vascular graft 110 described above with respect to FIGS. 2A-5C is equally applicable to the bifurcated vascular graft 110 shown in FIGS. 6A-6C.

[0061] Referring now to FIGS. 7A-7C, top views (FIG. 7A), top wireframe views (FIG. 7B), and side wireframe views (FIG. 7C) of an embodiment of the support structure of the vascular graft shown in FIGS. 1B, 6A-6C are shown, with a second inflow opening 33 attached to the graft body and depicting a support structure with only at least one inflow opening 32 (see, e.g., FIG. 5A) and an outflow opening 34 (see, e.g., FIG. 5C) before forming the branched vascular graft 10' shown in FIGS. 1B and 6A-6C. As will be understood by those skilled in the art, the support structure 40 characterized in FIGS. 7A-7C includes all of the relevant features of the vascular graft 10' shown in FIGS. 6A-6C. FIG. 7A shows a properly scaled illustration of the support structure 40, showing the precise relative proportions of the support structure and its strut / stent pattern. As shown in the exemplary embodiments in FIGS. 7A-7B, the support structure also includes a junction opening 37 to which a hollow branched conduit 99 is connected. The junction opening 37 of the branched conduit 99 and the second inflow opening 33 are in fluid communication with at least one inflow opening 32 and an outflow opening 34. As shown in the example in FIG. 7A, the support structure 40 terminates at one or more blunt ends 41, which can, for example, prevent or minimize damage to the biocompatible layer 50 caused by the support structure 40. The blunt ends 41 can be formed in a keyhole-like shape as shown in FIG. 7A, or in any other shape that enables the blunt ends 41 to prevent or minimize damage to the biocompatible layer 50 by the support structure 40.

[0062] To facilitate attachment of the branched conduit 99 at the junction opening 37 and its second inflow opening 33 to the body region 43 of the support structure 40, a recess 39 is provided in the contour of the body region 43 of the support structure 40 as in the exemplary embodiment illustrated in FIG. 7C. The branched conduit may then be sewn, sintered, or otherwise attached to the body region 43 at the recess 39.

[0063] Referring now to FIGS. 9A - 9H, various views of another embodiment of a branched blood vessel graft 410 are shown, similar to those shown in FIGS. 1B, 6A - 6C, having a branched conduit 99 with a pre - fabricated and pre - expanded expanded configuration at a second inflow opening 33 of the branched conduit 99 prior to implantation. Except for this expanded configuration, the blood vessel graft 410 may have the same structure, components, and configuration as that of the blood vessel graft 110 of FIGS. 1B and 6A - 6C. This pre - fabricated and pre - expanded expanded configuration anchors to an adjacent conduit body 43 and provides rigidity and structure. The expanded ends may also facilitate blood vessel attachment and implantation. FIG. 9A shows a side view of an embodiment of a support structure 40 of the branched blood vessel graft 110 shown in FIGS. 1B, 6A - 6C, illustrating the support structure 40 prior to combining with a biocompatible layer 50 to form a wall 30. FIG. 9B shows a schematic view of an embodiment of the branched blood vessel graft 110 shown in FIGS. 1B, 6A - 6C after combining the support structure 40 shown in FIG. 9A with the biocompatible layer 50 to form a wall 30. FIG. 9C shows a schematic view of an embodiment of the branched blood vessel graft 410 structure shown in FIGS. 1B and 6A - 6C after expanding an outflow end 36 of the support structure 40 of the branched blood vessel graft 410 shown in FIG. 9B. FIG. 9D is a photograph showing a prototype of an example of the embodiment of the support structure 40 shown in FIG. 9A. FIG. 9E is a photograph of a prototype of an example of the embodiment of the branched blood vessel graft shown in FIG. 9B, depicting an effective outer diameter dimension D con constrained along an outflow region 42. FIG. 9F is a photograph of a prototype of an example of the embodiment of the branched blood vessel graft shown in FIG. 9C, depicting an expanded effective outer diameter dimension D exp along the outflow region 42 and an expanded effective outer diameter dimension D exp along an inflow region 44 proximal to the second inflow opening 33. FIG. 9G is another photograph similar to FIG. 9F, further illustrating a boundary 94 used in FIG. 9H to schematically show a detailed view of a representative cross - section of the embodiments of FIGS. 9B and 9C.

[0064] Referring to FIG. 9G, the extending conduit 51 is shown assembled to an expanded socket-like structure. Using the expanded second inflow opening 33, the extending conduit can connect to the luminal surface of the branched conduit 99 when the branched conduit has a biocompatible layer coated on one or both of the inner and outer surfaces of the support structure of the branch. When the extending conduits each have a wall 89 that is thicker than the wall thicknesses 87 and 88 of the inner biocompatible layer 55 and the outer compatibility layer 54, respectively, the enlarged inner diameter of the branch provides sufficient space for the extending conduit to have a diameter that is substantially the same as the inner lumen diameter of the branched conduit, either in whole or at least in large part.

[0065] One of ordinary skill in the art can understand that in the exemplary embodiments shown in FIGS. 9A-9G, the various features of the branched vascular graft 110 and the support structure 40 function in substantially the same manner as those described in the foregoing related paragraphs.

[0066] According to one exemplary embodiment, the vascular graft 110 is a conduit 20 having a wall 30, with at least one inflow opening 32 at the inflow end 35 in the body region 43 and an outflow opening 43 at the outflow end 36 in the outflow region 42 that is opposite to at least one inflow opening 32. The wall 30 includes a support structure 40 and a biocompatible layer 50. Here, prior to combining with the biocompatible layer 50 to form the wall 30, the support structure 40 has a constant effective outer diameter dimension D along the body region and an effective outer diameter dimension D along the outflow region that gradually increases in each section along the support structure 40 that becomes gradually more distal from at least one inflow opening 32. c The support structure 40 has a plurality of effective outer diameter dimensions along its length. Here, after combining with the biocompatible layer 50 to form the wall 30, the support structure 40 within the outflow region 42 has a constrained effective outer diameter dimension D such that the support structure 40 within the outflow region does not gradually increase in each section along the support structure that becomes gradually more distal from at least one inflow opening. inc conMaintained under a continuous compressive stress S resulting from a continuously applied load generated by the biocompatible layer, and here, after application of the reaction force to the support structure 40 within the outflow region 42, the outflow region 42 has a constrained effective outer diameter dimension D con from which at least a portion thereof has a constrained effective outer diameter dimension D con to a reconstructed effective outer diameter dimension D that is at least 1 millimeter greater than the constrained effective outer diameter dimension D exp and includes a conduit 20.

[0067] The linear and branched or T-shaped vascular grafts of the present invention (e.g., grafts 10 and 110) can be used for various applications, as may be apparent to those skilled in the art, for example, for replacement or bypass of diseased vessels in patients suffering from occlusive or aneurysm diseases, in trauma patients requiring vascular replacement, for dialysis access, during surgical anastomosis or other vascular procedures routinely performed by medical practitioners, to improve fluid dynamics and reduce arterial blood pressure.

[0068] During operation, the vascular grafts of the present teachings (e.g., grafts 10 and 110) are deployed for implantation into a body passageway (e.g., a blood vessel). Embodiments of the invention contemplate any operative method for safely and effectively deploying the vascular graft 10 / 110 for implantation into a body passageway. Suitable methods will be apparent to a skilled medical practitioner. For example, one known method of deploying such a graft is the combined use of a sheath and a frangible line or “rip code.” The graft is preferably contained within one or more sheaths in a compressed state such that the outer diameter of the sheath(s) is less than or equal to 2 millimeters smaller than the blood vessel into which the graft (or graft portion) is intended to be implanted for delivery to a desired location. Once properly positioned, the code is pulled, separating the sheath along the frangible line, and the sheath is then unwound and removed from the graft, at least in part, due to the self-expanding quality of the graft, leaving the graft in place. This general method of using a single sheath to deploy a graft is well known in the art and thus requires no further explanation.

[0069] Once implanted within the body passageway, the outflow region 42 of the vascular graft 10 can be expanded to maintain or restore graft patency even after a long duration has elapsed from the original implantation time (e.g., weeks, months, years). For example, if a portion of the graft becomes crushed (e.g., due to in-growth of tissue and eventual thrombosis), stenosed, or sustains intimal hyperplasia, patency can be restored by expanding the outflow region 42 of the vascular graft 10 in accordance with the methods of the invention described herein.

[0070] Figures 10A and 10B are schematic views of an expandable device used to expand the outflow region 42 of an embodiment of a vascular graft 10 having a branched structure, but may also be employed for a non-branched structure. More specifically, FIG. 10B is a detailed view obtained around the boundary 86 of FIG. 10A. In the embodiment shown in FIGS. 10A-10B, the expandable device comprises a balloon catheter 98 with a balloon 97. However, one of ordinary skill in the art can understand that any expandable device capable of applying a reaction force with a radially expanding force can be used. FIGS. 10A-10B are also useful with respect to the installation of the graft 110 illustrated in this embodiment.

[0071] FIG. 11 is a photograph demonstrating an expandable device 86 used to expand the outflow region 42 of a vascular graft 110 having a branched structure. The expandable device would be equally applicable to a straight vascular graft such as the vascular graft 10.

[0072] One of ordinary skill in the art can readily envision various methods for expanding the outflow region 42 of the vascular graft 10.

[0073] According to an exemplary embodiment, a method 100 for expanding the outflow region 42 of a transplanted vascular graft 10 generally includes: (a) identifying or providing a vascular graft 10 having a support structure configured with an expanded outflow region 42 in accordance with any aspect of the present invention, step 102; and (b) applying a reaction force 108 to the support structure 40 within the expanded outflow region 42 to expand the outflow region 42.

[0074] In step 102, the implanted vascular graft 10 is a conduit 20 having a wall 30, with at least one inflow opening 32 at the inflow end 35 of the body region 43 and an outflow opening at the outflow end of the outflow region 42 opposite the at least one inflow opening 32, where the wall comprises a support structure 40 and a biocompatible layer 50, and where the support structure 40 within the outflow region 42 is under a compressive stress S resulting from the applied load exerted by the biocompatible layer 50, and comprises the conduit 20. In step 108, the step of applying a reaction force to the support structure 40 within the outflow region 42 is from a constrained effective outer diameter dimension D con to an expanded effective outer diameter dimension D con that exceeds the constrained effective outer diameter dimension D exp to reconfigure the support structure 40 within the outflow region 42, thereby expanding the outflow region 42 of the implanted vascular graft 10.

[0075] FIG. 12 shows a flow diagram depicting an exemplary embodiment of a method 100 for expanding the outflow region 42 of a vascular graft 10 according to one aspect of the present invention.

[0076] As shown in the exemplary embodiment in FIG. 12, the method for expanding the outflow region 42 of the implanted vascular graft 10 includes steps 102 through 108. Step 102 includes (a) the step of identifying the implanted vascular graft 10 described herein. Step 108 is performed to expand the implanted vascular graft 10 identified in step 102. Step 108 includes (b) the step of applying a reaction force to the support structure 40 within the outflow region 42 according to the detailed description herein, thereby expanding the outflow region 42 of the implanted vascular graft 10.

[0077] The expandable outflow region 42 can be expanded at any time after transplantation. In practice, it should be understood that the outflow region is advantageously expanded when the outflow region 42 is crushed or stenosed, or when it has persistent intimal hyperplasia. In such cases, the crushed, stenosed, or persistently intimal hyperplastic outflow region 42 impairs the patency of the vessel in which the implantable vascular graft 10 is implanted.

[0078] In an exemplary embodiment, the step of applying a reaction force includes expanding an expandable device within the outflow region 42 of the implanted vascular graft 10. In an exemplary embodiment, prior to expanding the expandable device (step 108), the expandable device is advanced to the outflow end (step 106).

[0079] In an exemplary embodiment, prior to advancing the expandable device to the outflow region (step 106), the expandable device is introduced percutaneously into the implanted graft (step 104). In an exemplary embodiment, after expanding the expandable device 10, the expandable device is removed according to step 110.

[0080] In an exemplary embodiment, the expanded effective outer diameter dimension D exp is at least 1 millimeter greater than the constrained effective outer diameter dimension D con In another exemplary embodiment, the expanded effective outer diameter dimension D exp is at least 1 millimeter greater than the constrained effective outer diameter dimension D con along any portion of the support structure 40 within the outflow region 42.

[0081] Contemplated herein are various methods for fabricating the vascular graft 10 disclosed herein.

[0082] FIG. 13 is a flow diagram depicting an exemplary method 200 for fabricating a vascular graft 10 in accordance with one aspect of the present invention.

[0083] In an exemplary embodiment, a method 200 of making a vascular graft 10 having an expandable outflow region includes steps 202 through 209. In the example shown in FIG. 13, the method 200 begins with (a) providing a support structure (step 202) comprising at least one inflow opening 32 at an inflow end 35 of a body region 43 and an outflow opening 34 at an outflow end 36 of the outflow region 42 opposite the at least one inflow opening 32 in accordance with the detailed description provided herein. The support structure 40 is sized through the use of various mandrels to provide a gradually increasing effective outer diameter dimension D along the outflow region 42 of the support structure. inc In addition, the support structure 40 has a constant effective outer diameter dimension D along the body region 43. c It should be understood by one of ordinary skill in the art that the support structure 40 provided in step 202 can include any support structure 40 contemplated herein, including the embodiments shown in Figures 2A, 5A, 7A, and 8A, which may include inflow region 44 or outflow region 42 with the flared configurations illustrated in Figures 3A-3O, or any combination thereof.

[0084] Once the support structure 40 is provided in step 202, the method 200 proceeds to step 204, which includes (b) combining the support structure 40 with at least one biocompatible layer 50 to form a conduit 20 having a wall 30 comprising the support structure 40 and the at least one biocompatible layer 50.

[0085] After combining the support structure 40 and the biocompatible layer 50 in step 204, the method proceeds to step 206, which includes (c) inserting a mandrel into the outflow opening 34 proximal to the outflow end 36 of the support structure 40.

[0086] Once the mandrel is inserted into the outflow opening 34, the method further comprises: (d) applying a continuous compressive stress S to the support structure 40 along the outflow region 42 to a constant effective outer diameter dimension D c and the substantially uniform effective outer diameter D conTo maintain, for example, by using compression wrapping, an effective outer diameter dimension D that increases gradually along the outflow region 42 of the support structure 40, as resulting from the continuous applied load generated by the biocompatible layer 50 inc Proceed to step 208, including the step of constraining.

[0087] To adapt the biocompatible layer 50 to the support structure 40, this method includes step 209 of sintering the biocompatible layer 50 in a certain section within the outflow region 42.

[0088] FIG. 14A is a photograph illustrating step 206 of a method 200 for fabricating a vascular graft 10 according to one aspect of the present invention, where the mandrel is inserted into the outflow end 36 of the vascular graft 10 prior to constraining the effective outer diameter dimension along the outflow end 40 of the support structure using compression wrapping.

[0089] FIG. 14B is a photograph illustrating step 206 of a method 200 for fabricating a vascular graft 10 according to one aspect of the present invention, where compression wrapping is used to constrain the effective outer diameter dimension along the outflow end of the support structure 40.

[0090] In another exemplary embodiment of the present invention, a vascular graft 510 is illustrated in FIGS. 15A - C. The graft 510 is formed by a pair of branched graft sub - assemblies 302a and 302b (collectively, "branched sub - assembly 302") that are arranged as mirror images of each other and connected by an extending conduit 51. The branched sub - assemblies 302 may each be arranged as illustrated, similar to the branched vascular graft 110. As will be discussed in more detail with respect to FIGS. 16A - 16C and 17A - 17C, further, the vascular graft embodiment can be formed by exchanging one or both of the branched sub - assemblies 302 with a graft sub - assembly similar to the graft 10. Thus, the components of the graft 510 similar to those of the graft 10 and / or 110 (e.g., conduit 20, wall 30, support structure 40, biocompatible layer 50, etc.) are correspondingly given the same reference numbers as those used in the foregoing discussion of the grafts 10 and 110.

[0091] FIG. 15A illustrates a branched subassembly without the biocompatible layer 50, while FIG. 15B illustrates the branched subassembly, and both the biocompatible layer 50 and the extending lumen 51 establish a continuous conduit between the subassemblies. In various embodiments, the extending lumen 51 may be a multi-layer laminate of ePTFE and may have a thickness 89 that exceeds the thicknesses of the inner layer 55 and the outer layer 54 of the biocompatible layer 50.

[0092] As shown in FIG. 15C, the branched subassemblies 302a and 302b are each insertable within a first vascular portion 306a and a second vascular portion 306b (collectively, the vascular portions 306). The conduit segment 51 is arranged as a lumen structure that provides fluid communication, e.g., blood flow, between the branched subassemblies 302 and thus between the vascular portions 306. Due to the branching of both subassemblies 302, at least a portion of the blood flow, i.e., the blood flow that is not diverted into the conduit segment 51, may also continue through and beyond the subassemblies 302. The wall 30 of the conduit segment 51 may be unreinforced, i.e., may not include the support structure 40 and may include only the biocompatible layer 50. It should be understood that the conduit segment 51 may be of any desired length. For example, a relatively shorter length may be used in some embodiments, e.g., to bridge or bypass an occlusion within a blood vessel, while a relatively longer length may be used in other embodiments, e.g., to connect an artery and a vein to assist with dialysis. In one embodiment, the conduit segment 51 is from about 20 mm to 150 mm, although other lengths are also possible.

[0093] It should be understood that the graft 510 may be used in embodiments where the vasculature 306 is different portions of the same vasculature, or where the vasculature portion 306 is portions of different vasculatures. For example, if the vasculature portion 306 is a portion of the same vasculature, the graft 510 may be used to create a bypass of a section of the vasculature located between the vasculature portions 306a and 306b. For example, an occlusion such as plaque buildup may completely or partially impede or block blood flow within a patient's blood vessels. In this example, the graft 510 may thus be installed such that the conduit section 51 provides a bypass of the occlusion when the subassembly 302 is installed within the blood vessels on either side of the occlusion.

[0094] As another example, in one embodiment, one of the vasculature portions 306 (e.g., vasculature 306a) is a portion of an artery and the other of the vasculature portions (e.g., vasculature 306b) is a portion of a vein. Thus, the conduit section 51 diverts a portion of the blood flowing through the artery into the vein. For example, this embodiment may be particularly useful in that the conduit section 51 provides a suitable target for assisting a patient during dialysis, such that the blood is diverted between the artery and the vein, removed from the conduit section 51, and re-injected therein, thus avoiding unnecessary damage to the patient's vasculature that may result from repeated dialysis treatments. In such an embodiment, the ability of the conduit section 51 to seal after needle puncture is enhanced relative to the properties of the vascular graft 510 that may be coated with a thinner material used within the conduit section 51.

[0095] The vascular graft 610 is illustrated in FIGS. 16A - 16C and generally resembles the graft 510, including, for example, a pair of graft sub - assemblies 312a and 312b (collectively, "sub - assembly 312") that are both connected by the conduit section 51. Unlike the graft 510 where both sub - assemblies 302 resemble the branched graft 110 of FIG. 1B, the sub - assembly 312b of the graft 610 is generally a linear graft sub - assembly that resembles the linear vascular graft 10 of FIG. 1A, while the sub - assembly 312a is a branched graft sub - assembly that resembles the graft 110. It should be noted that due to the lack of branching in the sub - assembly 312b in this embodiment, the blood flow through the vascular section 306b can be blocked or impeded by the sub - assembly 312b. That is, all or most of the blood flow through the vascular section 306b flowing in the direction from the sub - assembly 312b to the sub - assembly 312a can be diverted through the conduit section 51 instead of continuing through the vascular section 306b. Thus, the graft 610 is particularly advantageous in embodiments where, for example, the vascular sections 306 are part of the same blood vessel and there is an occlusion therebetween, and thus a bypass of that occlusion is desired, and where blood flow through the vascular sections 306b on both sides of the sub - assembly 312b is not required.

[0096] The vascular graft 710 is illustrated in FIGS. 17A - 17C and generally resembles the graft 510 and / or 610, including, for example, a pair of graft sub - assemblies 322a and 322b (collectively, "sub - assembly 322") that are both connected by the conduit section 51. Similar to the sub - assembly 312b of the graft 610, both sub - assemblies 322 are linear graft sub - assemblies that resemble the graft 10 without branching. For this reason, similar to the sub - assembly 312b, both sub - assemblies 322 can block or impede the blood flow through the individual vascular sections 306 into which they are inserted. Thus, the graft 710 can be particularly useful in embodiments where there is an occlusion between the vascular sections 306 and thus a bypass of that occlusion is desired.

[0097] It should be understood that sub - assemblies 510, 610, and 710 may include tapered, trumpet - shaped, or expanded inflow and / or outflow regions in accordance with the foregoing description. That is, the support structure 40 within sub - assemblies 510, 610, and / or 710 may be arranged and constructed from nitinol or other shape - memory materials or, alternatively, may be configured to naturally transition to a radially expanded shape. Additionally, the support structure 40 may be further radially expanded by the use of an inflatable balloon 97 or other device inserted within the support structure 40, as per the foregoing disclosure herein.

[0098] Numerous modifications and alternative embodiments of the present invention may be apparent to those skilled in the art in light of the foregoing description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the best mode for practicing the invention. The details of the structure may vary substantially without departing from the spirit of the invention, and the exclusive use of all modifications within the scope of the appended claims is reserved. Although the embodiments are described herein in a manner enabling them to be written clearly and concisely, it is intended, and should be understood, that the embodiments may be variously combined or separated without departing from the invention. The present invention is intended to be limited only by the scope required by the appended claims and the rules of applicable law.

[0099] Also, it should be understood that the following claims cover not only all the general and specific features of the invention described herein, but also all statements that can be said to be within the scope of the invention in a literal sense.

Claims

1. A graft configured for implantation in a living body, comprising: a support structure defining a first internal lumen extending from a first inflow opening to an outflow opening, the support structure including a tapered outflow end extending along a first portion of the length of the support structure from a proximal end to a distal end at the outflow opening, the tapered outflow end being movable between a first condition and a second condition, in the first condition a diameter of the tapered outflow end increases from a first diameter to a second diameter, the first diameter being equal to a diameter of a second portion of the support structure extending from the proximal end to the first inflow opening, the second diameter being greater than the first diameter at the distal end, and in the second condition a diameter of the tapered outflow end is substantially equal to the first diameter from the proximal end to the distal end; a biocompatible layer disposed about an exterior surface of the support structure, the biocompatible layer being configured, when disposed about the support structure in an insertion configuration, to apply a radial compressive force to the support structure to move the support structure from the first state to the second state; Equipped with The tapered outflow end is configured to move from the second state to the first state when a radial expansion force is applied to the inner surface of the support structure, whereby the tapered outflow end overcomes the radial compressive force applied by the biocompatible layer and expands to the second state.

2. The graft of claim 1 further comprising a second inflow opening between the first inflow opening and the outflow opening.

3. 3. The graft of claim 2, wherein the length of said support structure between said second inflow opening and said tapered outflow end is at least 100 millimeters.

4. 2. The graft of claim 1, wherein a first compressive force applied by the biocompatible layer to the first portion of the support structure is greater than a second compressive force applied by the biocompatible layer to the second portion of the support structure.

5. The graft of claim 1, wherein the compressive stress applied to the tapered outflow end gradually increases in one or more initial segments along the length of the support structure and then becomes substantially constant along each segment that progresses progressively away from the one or more initial segments.

6. The graft of claim 1 , wherein a compressive stress applied to the tapered outflow end causes the tapered outflow end to elastically deform toward the second condition.

7. The graft of claim 6, wherein the elastic deformation of the tapered outflow end increases in one or more initial segments along the support structure and then becomes substantially constant over each segment that progresses progressively away from the one or more initial segments.

8. The graft of claim 7 , wherein the support structure is configured such that elastic deformation of the tapered outflow end is reversible.

9. 7. The graft of claim 6, wherein said tapered outflow end is expanded to said first condition by reversing elastic deformation of said tapered outflow end.

10. 3. The graft of claim 2, wherein the second inflow opening opens the first lumen to a second lumen extending at an angle to a longitudinal axis of the first lumen.

11. The graft of claim 10, wherein the angle is between about 25° and 45°.

12. The graft of claim 10, wherein the angle is about 35 degrees.

13. The graft of claim 10 , wherein the first and second lumens are not perpendicular to each other at the second inflow opening.

14. The graft of claim 1 , wherein the support structure is constructed from a shape memory alloy.

15. The graft of claim 1 , wherein the support structure is constructed from Nitinol.

16. The graft of claim 1 , wherein the biocompatible layer comprises an expandable polymer.

17. The graft of claim 1 , wherein the biocompatible layer comprises ePTFE.

18. The graft of claim 1 , wherein the biocompatible layer further comprises a biocompatible outer layer.

19. The graft of claim 18, wherein the biocompatible layer further comprises a biocompatible inner layer radially inward of the support structure.

Images