WO2024009265A1

WO2024009265A1 - Compliant vascular grafts and methods of use

Info

Publication number: WO2024009265A1
Application number: PCT/IB2023/057011
Authority: WO
Inventors: Georgios ROVAS; Nikolaos Stergiopulos
Original assignee: Ecole Polytechnique Federale De Lausanne (Epfl)
Priority date: 2022-07-08
Filing date: 2023-07-06
Publication date: 2024-01-11

Abstract

Compliant vascular grafts for implantation in the vasculature are provided. The compliant vascular grafts are designed to expand longitudinally and radially within a blood vessel, such as an artery, and is expected to be particularly well suited for treating aneurysms in challenging anatomy such as the thoracic aorta. The compliant vascular grafts preferably have an outer frame layer and an inner graft layer with a plurality of pleats to permit expansion.

Description

COMPLIANT VASCULAR GRAFTS AND METHODS OF USE

I. Cross-Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Patent Application No. 63/367,985, filed July 8, 2022, the entire contents of which are incorporated herein by reference.

II. Technical Field

[0002] This technology generally relates to implantable medical devices such as compliant vascular grafts for implantation in the vasculature.

III. Background

[0003] The treatment for multiple severe conditions that affect large arteries, such as aneurysms, requires surgical replacement with synthetic vascular grafts. Synthetic grafts, despite their widespread adoption, are often associated with increased drug administration and serious post-operative complications, including hypertension and myocardial hypertrophy. The complications are partly caused by non-physiological graft stiffness since standard aortic grafts are multiple times stiffer than a healthy human aorta, a phenomenon often termed as “compliance mismatch”. Gold-standard grafts are usually made from PET, PTFE, or PU fibers that are either woven or knitted. Such grafts have been in use for more than 50 years with only minor improvements.

[0004] U.S. Patent No. 5,476,506 to Lunn shows a graft with a central portion that is longitudinally extendable and end portions that are radially extendable. The portions with different properties may lead to plaque or unhealthy endothelial formation on the border zone between regions.

[0005] U.S. Patent No. 5,282,847 to Trescony shows a graft with corrugated pleats. Such a graft cannot accommodate the longitudinal motion imposed by the heart and the potential prestretch imposed during surgery. These grafts are also vulnerable to kinking when bent. Further, the required twisting to increase kinking resistance is impractical during surgery and the twist will be transferred to the arteries that are usually more flexible than the graft, thereby increasing the load on the attachment/suture points.

[0006] U.S. Patent No. 6,626,938 to Butaric describes a graft with longitudinal pleats used to facilitate compression before intravascular delivery. With this design, longitudinal motion is hindered and bending such a graft (e.g., for aortic arch repairs) could also be problematic due to the stent configuration.

[0007] Additional references include U.S. Patent Nos. 6,652,570 to Smith et al., US 8,118,856 to Schreck et al., US 9,579,187, US 9,839,510 to Shalev, US 10,893,929, WO 0152771 Al, WO 2006054968 Al, loannou, C. V., Morel, D. R., Katsamouris, A. N., Katranitsa, S., Startchik, I., Kalangos, A., Westerhof, N., & Stergiopulos, N. (2009). Left Ventricular Hypertrophy Induced by Reduced Aortic Compliance. Journal of Vascular Research, 46(5), 417-425. https://doi.org/10.1159/000194272, Langewouters, G. J., Wesseling, K. H., & Goedhard, W. J. A. (1984). The static elastic properties of 45 human thoracic and 20 abdominal aortas in vitro and the parameters of a new model. Journal of Biomechanics, 17(6), 425-435. https://doi.org/10.1016/0021-9290( 84)90034-4, Lucereau, B., Koffhi, F., Lejay, A., Georg, Y., Durand, B., Thaveau, F., Heim, F., & Chakfe, N. (2020). Compliance of Textile Vascular Prostheses Is a Fleeting Reality. European Journal of Vascular and Endovascular Surgery, 0(0). https://doi.Org/10.1016/j.ejvs.2020.07.016, Pagoulatou, S. Z., Ferraro, M., Trachet, B., Bikia, V., Rovas, G., Crowe, L. A., Vallee, J.-P., Adamopoulos, D., & Stergiopulos, N. (2021). The effect of the elongation of the proximal aorta on the estimation of the aortic wall distensibility.

Biomechanics and Modeling in Mechanobiology, 20(1), 107-119. https://doi.org/10.1007/sl0237-020-01371-y, Plonek, T., Berezowski, M., Kurcz, J., Podgorski, P., S^siadek, M., Rylski, B., Mysiak, A., & Jasinski, M. (2018). The evaluation of the aortic annulus displacement during cardiac cycle using magnetic resonance imaging. BMC Cardiovascular Disorders, 18(1), 154. https://doi.org/10.1186/sl2872-018-0891-4, Spadaccio, C., et al., ‘Old Myths, New Concerns: the Long-Term Effects of Ascending Aorta Replacement with Dacron Grafts. Not All That Glitters Is Gold’, Journal of Cardiovascular Translational Research, vol. 9, no. 4, pp. 334-342, Aug. 2016, doi: 10.1007/sl2265-016-9699-8, Vardoulis, O., Coppens, E., Martin, B., Reymond, P., Tozzi, P., & Stergiopulos, N. (2011). Impact of Aortic Grafts on Arterial Pressure: A Computational Fluid Dynamics Study. European Journal of Vascular and Endovascular Surgery, 42(5), 704-710. https://doi.Org/10.1016/j.ejvs.2011.08.006.

[0008] In view of the foregoing, there is a need for improved vascular grafts.

IV. Summary

[0009] Provided herein are systems and methods for treating vascular conditions using compliant vascular grafts. The compliant vascular grafts may be used to treat multiple severe conditions that affect large arteries, such as aneurysms. The compliant vascular grafts may be used as a complete replacement for a section of the affected large artery.

[0010] In accordance with some aspects, a compliant vascular graft for implantation in a blood vessel is provided that may include an inner graft layer and an outer frame layer disposed outside the inner graft layer. The inner graft layer includes a tubular body defining a lumen that permits blood flow therethrough. Preferably, the inner graft layer includes a plurality of longitudinal pleats along a longitudinal axis of the tubular body to permit longitudinal expansion and a plurality of radial pleats to permit radial expansion. The inner graft layer and the outer frame layer are configured to transition from a longitudinally and radially contracted state to a longitudinally and radially expanded state via expansion of the plurality of longitudinal pleats and the plurality of radial pleats while implanted in the blood vessel.

[0011] The outer frame layer may compress the inner graft layer circumferentially while allowing the inner graft layer to stretch longitudinally. The outer frame layer allows the inner graft layer to bend and to twist without kinking. Preferably, at least a portion of the plurality of longitudinal pleats overlaps with the plurality of radial pleats. In some embodiments, the plurality of longitudinal pleats and the plurality of radial pleats extend along an entire length of the compliant vascular graft. The inner graft layer may have a larger diameter than the outer frame layer.

[0012] The compliant vascular graft may be configured to be implanted in a thoracic aorta or abdominal aorta. The compliant vascular graft may have radial and longitudinal compliance tailored to mimic compliance of a healthy thoracic aorta. [0013] The compliant vascular graft may transition between the longitudinally and radially contracted state and the longitudinally and radially expanded state responsive to pressure changes in the blood vessel during the cardiac cycle to mimic compliance of a healthy version of the blood vessel (e.g., a healthy aorta).

[0014] The outer frame layer may include a plurality of rings. Each of the plurality of rings may have a zigzag shape. The spacing between the plurality of rings may increase from the longitudinally and radially contracted state to the longitudinally and radially expanded state. In some embodiments, the plurality of rings are not connected to one another. The outer frame layer further may include longitudinal struts that couple adjacent rings of the plurality of rings. The longitudinal struts may be straight or zigzag shaped. The outer frame layer may have a helical shape. In some embodiments, a majority of the outer frame layer is not coupled to inner graft layer.

[0015] The inner graft layer and the outer frame layer may self-expand from the longitudinally and radially contracted state to the longitudinally and radially expanded state. The inner graft layer and the outer frame layer may be configured to be balloon expanded from the longitudinally and radially contracted state to the longitudinally and radially expanded state.

[0016] In accordance with another aspect, a method of using a compliant vascular graft for implantation in a blood vessel is provided. The method may include selecting a compliant vascular graft comprising an inner graft layer and an outer frame layer disposed outside the inner graft layer, the inner graft layer comprising a tubular body defining a lumen that permits blood flow therethrough, the inner graft layer comprising a plurality of longitudinal pleats along a longitudinal axis of the tubular body to permit longitudinal expansion and a plurality of radial pleats to permit radial expansion; and implanting the compliant vascular graft in the blood vessel such that the inner graft layer and the outer frame layer transition from a longitudinally and radially contracted state to a longitudinally and radially expanded state via expansion of the plurality of longitudinal pleats and the plurality of radial pleats while implanted in the blood vessel. After implantation, the compliant vascular graft may transition between the longitudinally and radially contracted state and the longitudinally and radially expanded state responsive to pressure changes in the blood vessel during the cardiac cycle to mimic compliance of a healthy version of the blood vessel.

V. Brief Description of the Figures

[0017] The foregoing and other objects, features, and advantages of the description set forth herein will be apparent from the following description of particular embodiments of those inventive concepts, as illustrated in the accompanying drawings. It should be noted that the drawings are not necessarily to scale; emphasis instead is placed on illustrating the principles of the inventive concepts. Also, in the drawings, like reference characters may refer to the same parts or similar parts throughout the different views. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than limiting.

[0018] FIG. 1 A is a perspective view of an exemplary compliant vascular graft in a longitudinally and radially contracted state.

[0019] FIG. IB is a perspective view of the compliant vascular graft of FIG. 1A in a longitudinally and radially expanded state.

[0020] FIGS. 1C and ID are, respectively, side and front views of the compliant vascular graft of FIG. 1A in the longitudinally and radially contracted state.

[0021] FIGS. IE and IF are, respectively, side and front views of the compliant vascular graft of FIG. 1A in the longitudinally and radially expanded state.

[0022] FIG. 1G is a side view of the compliant vascular graft of FIG. 1 A in the longitudinally and radially contracted state and FIG. 1H is a zoomed in version of a section of FIG. 1G.

[0023] FIG. II is a front view of the compliant vascular graft of FIG. 1A in the longitudinally and radially contracted state and FIG. 1J is a zoomed in version of a section of FIG. II.

[0024] FIG. IK is a side view of the compliant vascular graft of FIG. 1 A in the longitudinally and radially contracted state and FIG. IL is a cross-sectional front view. [0025] FIG. 2 A is a perspective view of the compliant vascular graft of FIG. 1 A in the longitudinally and radially contracted state mounted on a balloon catheter.

[0026] FIGS. 2B and 2C are, respectively, front and side views of the compliant vascular graft of FIG. 1A in the longitudinally and radially contracted state mounted on the balloon catheter.

[0027] FIG. 3A is a perspective view of another exemplary compliant vascular graft in the longitudinally and radially contracted state.

[0028] FIGS. 3B and 3C are, respectively, side and front views of the compliant vascular graft of FIG. 3 A in the longitudinally and radially contracted state.

[0029] FIG. 4A is a perspective view of another exemplary compliant vascular graft in the longitudinally and radially contracted state.

[0030] FIGS. 4B and 4C are, respectively, side and front views of the compliant vascular graft of FIG. 4A in the longitudinally and radially contracted state.

[0031] FIG. 4D is a front view of an exemplary frame for the compliant vascular graft of FIG. 4A.

[0032] FIG. 5A is a perspective view of another exemplary compliant vascular graft in the longitudinally and radially contracted state.

[0033] FIGS. 5B and 5C are, respectively, side and front views of the compliant vascular graft of FIG. 5A in the longitudinally and radially contracted state.

[0034] FIGS. 6A-6B show the difference of the angle between stent-ring and inner layer for thin and wide stent-rings.

[0035] FIGS. 7-10B are graphs showing experimental results. VI. Detailed Description

[0036] Provided herein are multi-layer vascular graft that mimic arterial function and may be tailored to match the compliance of healthy arterial tissue. Exemplary compliant vascular grafts include a vascular graft as an inner layer and an outer frame layer (e.g., a stent-like metallic structure). The outer frame layer may include multiple independent elements with predefined spacing. The outer frame layer compresses the inner graft layer circumferentially while allowing the graft to stretch longitudinally, to bend and to twist without kinking. The inner layer preferably has larger diameter than the outer layer and has stored length in its longitudinal direction.

[0037] The compliant vascular grafts are expected to be particularly well suited for thoracic and abdominal aortic replacement, mainly by open procedures, but could be implemented as an endovascular stent-graft. The compliant vascular grafts have volumetric (radial and longitudinal) compliance that may be tailored to match the compliance of thoracic aorta, which is higher than that of abdominal aorta. These grafts solve post-operative hypertension, hypertrophy, and increased hemodynamic load that are induced by conventional grafts and is expected to lead to healthy endothelial tissue formation. The compliant vascular grafts provided herein are expected to reduce the need for extensive post-operative medication and increase patients’ quality of life and life expectancy.

[0038] The outer frame layer of the graft may include discrete rings with specified spacing instead of a continuous stent, allowing room for the anastomoses of vessels (e.g. carotid, subclavian) and bending/twisting of the graft. The ability to bend, twist, and longitudinally extend will facilitate an open surgical approach. Further, the compliance of the graft is ‘tunable’ and may be selected based on the patient (e.g., their age or their measured compliance) thus providing optimal coupling of elastomechanical properties. The graft has very low profile, similar to a standard graft. Preferably, the grafts have no gas or liquid chambers that, in the case of leakage, lose their functionality. The grafts may be cut to any length that is required without loss of functionality. Preferably, the grafts have no empty space or cavities between layers/parts, that if filled by blood or tissue could cause thrombus formation, loss of functionality, and risk of embolisms. [0039] The outer frame layer is expected to enhance the inner graft layer by increasing the graft’s compliance. The outer frame layer may be attached to the inner layer or, if there is enough friction between the layers, they can stay in place without any additional coupling.

[0040] The graft designs provided herein reach compliance levels that are found in the human aorta, even in those of young adults, thereby significantly exceeding the compliance of gold-standard grafts. The grafts are biocompatible and the rest of their mechanical properties, like burst pressure, are suitably safe and effective.

[0041] A computational model is also provided herein that could be used to create patientspecific grafts that optimally match the characteristics of each patient. Therefore, the grafts could reduce post-operative complications that are caused by compliance mismatch.

[0042] FIG. 1A-1L show various views of compliant vascular graft 100 constructed in accordance with aspects of the present invention. FIG. 1A shows compliant vascular graft 100 in a longitudinally and radially contracted state and FIG. IB shows compliant vascular graft 100 in a longitudinally and radially expanded state. Compliant vascular graft 100 preferably includes inner graft layer 102 and outer frame layer 104.

[0043] Inner graft layer 102 may be made from woven PET fibers, or any other material commonly found in arterial grafts. Inner graft layer 102 may be made from a single material or composed of multiple layers or materials, that are positioned: (a) stacked on top of each other (radially), (b) distributed longitudinally, or (c) a combination of (a) and (b). Inner graft layer has pleats along its axis to store length. Outer frame layer 104 may surround inner graft layer 102 in a stent-like exoskeleton manner. Outer frame layer 104 may be formed from a biocompatible metal, such as nickel-titanium, and may include rings that have smaller diameter than inner graft layer 102, forcing inner graft layer 102 to compress/collapse, as shown in FIG. 1A. Thereby, there is also stored length in the circumferential direction. The rings control the radial expansion and they allow the graft to expand longitudinally as well. The combined expansion leads to physiological levels of volumetric compliance. The rings may be secured in place with sutures, glue, chemical/thermal bonding, tape, external wrap or any other known, equivalent technique. The rings may be connected together in small groups as long as the connections do not impede the longitudinal motion. Outer frame layer 104 may be made from a single material or composed of multiple layers or materials, that are positioned: (a) stacked on top of each other (radially), (b) distributed longitudinally, or (c) a combination of (a) and (b). While compliant vascular graft 100 is described as being formed of inner graft layer 102 and outer frame layer 104, compliant vascular graft 100 could be composed by more than the two layers, either internally, externally or in-between the two described layers.

[0044] Compliant vascular graft 100 is preferably designed for implantation in a blood vessel, such as the aorta or peripheral or coronary arteries. Inner graft layer 102 has tubular body 106 defining lumen 108 that permits blood flow therethrough. Inner graft layer may be a synthetic graft or biological tissue (e.g. vein) or a combination of the two. Inner graft layer 100 preferably has a plurality of longitudinal pleats 110 along the longitudinal axis of tubular body 106 to permit longitudinal expansion and a plurality of radial pleats 112 to permit radial expansion. Outer frame layer 104 is disposed outside inner graft layer 102. Inner graft layer 102 and outer frame layer 104 transition from a longitudinally and radially contracted state to a longitudinally and radially expanded state via expansion of the plurality of longitudinal pleats 110 and the plurality of radial pleats 112 while compliant vascular graft 100 is implanted in the blood vessel. In some embodiments, radial pleats 112 give inner graft layer 102 a clover shape (e.g., 5-leafed clover, as shown in FIG. 1A) in the radially contracted state.

[0045] Outer frame layer 104 compresses inner graft layer 102 circumferentially while allowing inner graft layer 102 to stretch longitudinally. Further, outer frame layer 104 allows inner graft layer 102 to bend and to twist without kinking. As shown in FIG. 1A, at least a portion of the plurality of longitudinal pleats 110 overlaps with the plurality of radial pleats 112. They may overlap along the entire length of compliant vascular graft 100. In some embodiments, the plurality of longitudinal pleats 110 and the plurality of radial pleats 112 extend along the entire length of compliant vascular graft 100. Inner graft layer 102 preferably has a larger diameter than outer frame layer 104.

[0046] Compliant vascular graft 100 is particularly well-suited to be implanted in a thoracic aorta or abdominal aorta. Compliant vascular graft 100 may have radial and longitudinal compliance tailored to mimic compliance of a healthy thoracic aorta. [0047] Compliant vascular graft 100 may transition between the longitudinally and radially contracted state and the longitudinally and radially expanded state responsive to pressure changes in the blood vessel during the cardiac cycle to mimic compliance of a healthy blood vessel, such as a healthy aorta.

[0048] Outer frame layer 104 may be formed of a plurality of rings 114. Each of the plurality of rings 114 may have a zigzag shape. As shown by comparing FIG. 1A to FIG. IB, spacing between the plurality of rings 114 may increase from the longitudinally and radially contracted state to the longitudinally and radially expanded state.

[0049] In some embodiments, a majority of outer frame layer 104 is not coupled to inner graft layer 102. For example, each ring 114 of outer frame layer 104 may be coupled to inner graft layer 102 at only a few spots along its circumference (e.g., a few stitches), while the majority of the ring remains uncoupled to inner graft layer 102.

[0050] Outer frame layer 104 may self-expand from the longitudinally and radially contracted state to the longitudinally and radially expanded state, thereby permitting inner frame layer 102 to also expand in a corresponding manner. For example, outer frame layer 104 may be formed from material having shape-memory properties such as nickel-titanium alloys or other shape-memory alloys.

[0051] As shown in FIGS. 1A and IB, the plurality of rings 114 are not connected to one another, in some embodiments. Thus, rings 114 are independently expandable relative to one another and by compression of inner graft layer 102, rings 114 control the compliance of compliant vascular graft 100. Since the material of inner graft layer 102 is compressed or under collapse both in the circumferential and in the axial direction, it has very low resistance to radial and longitudinal expansion respectively. The compliance of the two layers is the inverse of the inverse sum of the compliance of each layer. The compressed inner layer has very high compliance, but the outer layer has lower compliance. Therefore, the inner layer contributes very little to the total compliance. As a result, in this embodiment, the resulting compliance is nearly independent of the material of the inner layer, as long as the graft can slightly compress radially due to the force acting on it by the surrounding frame. Compliance of outer frame layer 104 is designed for a pressure range selected to align with normal human blood pressures in the selected blood vessel. A possible application, for example, is to increase the compliance when the rings are used in combination with other grafts.

[0052] Compliant vascular graft 100 may be manufactured with inner graft layer 102 extended longitudinally, which causes it to shrink in diameter. The stent-rings of outer frame layer 104 are then placed around the inner layers and they are secured in place with sutures, glue, chemical/thermal bonding, tape, or external wrap.

[0053] Referring to FIGS. 2A-2C, compliant vascular graft 100 may be compressed to be used for endovascular surgeries. When compliant vascular graft 100 is in place on a delivery device, a balloon or a similar device expands compliant vascular graft 100 to a diameter smaller or equal to its initial expanded diameter. FIG. 2A shows compliant vascular graft mounted on catheter 200 over balloon 202. Thus, inner graft layer 102 and outer frame layer 104 may be balloon expanded from the longitudinally and radially contracted state to the longitudinally and radially expanded state.

[0054] Referring now to FIGS. 3A-3C, alternative compliant vascular graft 100’ is shown. Compliant vascular graft 100’ is similar to compliant vascular graft 100 except the outer frame layer is modified. In particular, outer frame layer 104’ has rings 114’ that are connected with springs or elastic structures/bridges that allow longitudinal extension. For example, outer frame layer 104’ has longitudinal struts 300, 302 that couple adjacent rings 114’ of the plurality of rings 114’. Longitudinal struts may be radially offset from one another. Longitudinal struts 300 are straight while longitudinal struts 302 are zigzag shaped.

[0055] Referring now to FIGS. 4A-4C, alternative compliant vascular graft 100” is shown. Compliant vascular graft 100” is similar to compliant vascular graft 100 except the outer frame layer is modified. In particular, outer frame layer 104” has a helical shape. Outer frame 104” may be a continuous helical spiral, as shown in FIG. 4D, that compresses the inner layer. Alternatively, the rings could be placed at a different angle and not perpendicular to the axis of the graft. Supports between adjacent rings or spirals could also be added in the helical configuration, similar to the longitudinal struts shown in FIGS. 3A-3C. [0056] Referring now to FIGS. 5A-5C, alternative compliant vascular graft 100”’ is shown. Compliant vascular graft 100’” is similar to compliant vascular graft 100 except the outer frame layer is modified. In particular, outer frame layer 104’” has rings 114’” at opposing ends and a plurality of longitudinal struts 500 extending therebetween and spaced radially around inner graft layer 102’”. Pleasts of the inner layer may be placed circumferentially, and the frame compresses the inner layer longitudinally.

[0057] The compliant vascular grafts described herein are biocompatible and long-term biostable materials that have the required mechanical strength, suture retention strength, and a compliance similar to that of healthy arteries, especially at an internal pressure level of lOOmmHg, which corresponds to the mean arterial pressure of humans. A compressed material, even more so a material under bulking/collapse, has very low resistance/stiffness in the direction that tends to bring the material back to its free state. A thin-walled tube, such as a vascular graft, has very low resistance to radial bulking/compression. At the same time, the outer frame restricts/controls expansion by surrounding it with an external stiffer structure, since the compliance of two concentric surfaces in contact is the inverse of the inverse sum of the compliance of each surface — - — = — + — . Therefore, a single external layer can compress the

' Ctotal G c₂ ^{6 ? 1} internal layer but also control its expansion in order for the system to have compliance similar to healthy aortas. This is achieved without sacrificing the ability of the stent-graft to extend longitudinally. Longitudinal extension is necessary to mimic arterial function and to achieve volumetric compliance equal to that of thoracic aorta. The inner layer that has stored length in its axial direction and the frame can have fixed spacing that does not restrict the longitudinal extension.

[0058] The compliant vascular grafts herein are designed to bend and twist and have the ability to allow anastomoses on its surface, low profile, no chambers, no empty spaces, and may be cut to length. As such, the compliant vascular grafts have a volumetric compliance similar to that of healthy aortas.

[0059] Cardiac contraction is a rapid and intense mechanism that causes the heart to not only contract circumferentially, but to also move along its longitudinal axis (defined as the axis of the heart the axis that passes from the apex and from the center of the aortic valve). Equivalently, the heart, or the left ventricle, shrinks both in perimeter and in length. The longitudinal motion plays an important role in aortic compliance. Because the apex of the heart remains relatively stationary during the cardiac cycle, any change in length means that practically the heart is pulling the aorta towards the cardiac apex. This displacement is called longitudinal displacement of the aortic annulus and it has been measured experimentally and was found to be equal to 11.6 ± 2.9 mm (Plonek et al., 2018). Consequently, this displacement causes the elongation of the aorta and a small decrease in its diameter when the transition is isovolumic. Elongation of the aorta is a major component of its volumetric compliance Cv (C_v = dV/dP where V is the lumen volume and P is the equivalent intraluminal pressure). In fact, the elongation accounts for 24-62% of the volumetric compliance, depending on the aortic stiffness and the degree of aortic elongation of each individual. Therefore, conventional aortic grafts that have increased radial compliance CR (C_R = dr/dP where r is the lumen radius) will not have the necessary volumetric compliance, because they are not able to accommodate the heart-imposed elongation. Volumetric compliance is related with the radial compliance by the following equation: C_v = , , .. , the longitudinal

⁶ compliance and L is the length of the graft or vessel. The volume of blood has biological significance and not the vessel radius, since the cardiovascular system is three dimensional, the volume of blood is responsible for tissue perfusion and the body’s regulatory and homeostatic mechanisms react to changes in volume, or equivalently to perfusion, and not to changes in arterial radius. The maximum longitudinal displacement occurs in peak systole, the part of the heart cycle in which blood is pumped in the aorta and consequently the part where volumetric compliance is needed the most, in order for the graft to accommodate the volume of blood that is pumped in it. A graft with no longitudinal compliance, will have reduced volumetric compliance that decreases even further during systole. As a result, compliance mismatch will occur, and it will become augmented in the most crucial part of the heart cycle. Unlike conventional grafts, the compliant vascular grafts herein are truly artery-mimicking to provide optimal treatment to patients. The grafts mimic both the circumferential and the longitudinal arterial compliance.

[0060] The directions of stress in a material are dependent on one another. If a material is stressed in one direction and then stressed in a secondary direction, the loading on the second direction will not start from a zero-stress state, but there will be some pre-existing stress from the load in the first direction. Especially for materials consisting of fibers, such as vascular grafts, mechanical properties are highly anisotropic, so that stress in one direction significantly effects the properties of the material in all other directions. That is because fibers interact with each other through friction, tangling and other mechanisms. It is therefore much more difficult to stretch such a material in a second direction, when it is already stretched in another direction, because the fibers are already stretched in the first direction and they impede the elongation of the fibers in the second direction. This interdependence of mechanical properties is defined with the general constitutive equation for an anisotropic material:

[0061] In the case of vascular grafts, that simply means that if the graft is stretched longitudinally, its area compliance will be reduced significantly. Moreover, surgeons typically prestretch vascular grafts when they implant them to avoid kinking issues due to the graft’s minimal resistance to bending when unstretched. The prestretch also help in avoiding interference with other organs post implantation. The compliant vascular grafts herein, however, are flexible in both circumferential and longitudinal direction to match the volumetric compliance of a healthy aorta.

[0062] Referring now to FIGS. 6 A and 6B, the difference of the angle between stent-ring and inner layer for thin and wide stent-rings is shown.

[0063] The thoracic aorta has a more complicated geometry than the abdominal aorta. The abdominal aorta, especially the infrarenal part until the iliac bifurcation is a straight segment with no major branches. On the contrary, thoracic aorta is a curved vessel with approximately 180° curvature, with a small twist that is augmented by the movements of the heart and typically three major bifurcations. Conventional grafts do not deal with these restrictions and would not be suitable for application in the thoracic aorta. [0064] The stent-inner layer angle is important because if it exceeds a few degrees, the stent can damage the inner layer and perforate it with deleterious consequences. Thus, small, independent stent rings allow the graft to twist with ease, which is useful for the normal operation of the graft so that it accommodates the twisting motion imposed by the heart, and for the surgical procedure so that it makes the implantation easier. A thin, woven tube, such as a vascular graft, has very small twisting rigidity, but a stent, even more a large stent, is much more resilient to twisting. The combination of the two will cause the stents to not follow the twist of the graft, the stent will lag behind and that could cause rupture or detachment of the stent from the graft when the blood pressure is applied internally. Finally, small independent rings allow the anastomosis of all the necessary vessels into the graft. If the spacing between rings does not suffice, it is possible to remove only the minimum required number of rings to allow room for anastomoses, without significant reduction in the graft’s compliance. On the contrary, if the stents are bigger and/or they do not have enough space between them, removing one stent can significantly reduce the compliance of the graft.

[0065] Algorithms are also provided herein to predict with accuracy the resulting compliance to achieve the desired level compliance to optimally match the patient’s compliance, regardless of diameter and length. The algorithm can accurately predict the properties, namely the compliance, of the fabricated graft. This algorithm may be used to produce patient-specific grafts that optimally match the aortic compliance of each patient regardless of the graft’s dimensions. Therefore, the developed graft could potentially reduce post-operative complications that are caused by compliance mismatch.

[0066] A finite element model of this graft was created, based on the material properties derived from experiments. The model was subsequently utilized to perform design parameter optimization to increase the graft’s compliance. Then, the optimal graft was fabricated and inserted it in a hydraulic circuit to measure its compliance in vitro, by simultaneous acquisition of pressure, volume and radial deflection.

[0067] Experimental Results: [0068] FIG. 7 is a graph showing distensibility as a function of pressure for a gold-standard graft and for the compliant vascular grafts described herein. The shaded region represents typical distensibility levels of healthy adults.

[0069] The first prototypes were fabricated and tested in vitro in a mock circulatory system. The grafts reach an area compliance of 0.008 cm2/mmHg at 100 mmHg. The relation between distensibility (area-normalized compliance) and pressure of this graft, compared to gold-standard grafts and physiological levels of healthy human aortas can be seen in FIG. 7.

[0070] The computational model was validated against the experimental results. The developed model predicts the radius of the fabricated graft over the normal operating pressure range with a RMSE=0.0244mm and its compliance at 100 mmHg with an error of 7%.

[0071] FIG. 8 is a plot showing Aortic Pulse Wave Velocity (PWV) as measured invasively before aortic replacement in a healthy pig (Baseline) and after replacement with our graft (Compliant) and with a gold-standard dacron graft (Dacron).

[0072] Since the in vitro experiments produced encouraging results, acute in vivo experiments in pigs were conducted. The design was optimized based on the vascular characteristics of pigs and the grafts were implanted by replacing the ascending aorta and the aortic arch of healthy pigs. The outer frame was removed so that a gold-standard dacron graft remained in place. Pulse wave velocity (PWV) was measured, a clinical index of arterial stiffness, at baseline, with the inventive graft (compliant) and with the dacron graft. The results are very promising as shown in FIG. 8. The PWV remains at the same, healthy, level with the compliant graft while it increases multiple times with a standard dacron graft. Additionally, due to the reduced compliance, the pulse pressure increased significantly when the external frame was removed, thus causing the animal to become hypertensive.

[0073] FIG. 9 is a plot showing Area compliance for gold standard grafts (Control) versus the compliance matching graft (CM) at various levels of longitudinal prestretch, indicated as percentages.

[0074] Surprisingly, the device (CM) is significantly better than the gold-standard grafts (control) regardless of the level of pre-stretch applied to them and actually, the percentage increase in compliance increases with pre-stretch. In FIG. 9, the levels indicated as percentages represent the longitudinal pre-stretch. Typically, the grafts are pre-stretched during the implantation by the surgeon and they stretch even further when blood flows through them. For higher pre-stretch, the increase in compliance achieved by the compliant device is even greater and it does not reduce rapidly with pre-stretch, contrastingly to gold-standard grafts.

[0075] FIG. 10A is a graph showing internal radius of the graft versus internal pressure, as measured in vitro (experiment) and as estimated by the computational model (model).

[0076] FIG. 1 OB is a graph showing linear regression analysis of the model prediction versus the experimental data.

[0077] The algorithm for the prediction of the behavior of the compliant graft is also very precise and may be used to optimize the compliance of the graft, regardless of diameter and length until it reaches the desired levels, allowing the creation of tailored compliance-matching grafts. In FIG. 10A, the algorithmic model’s radius prediction and the experimental results versus the internal pressure are shown. FIG. 10B displays the regression analysis.

[0078] While various illustrative embodiments of the invention are described above, it will be apparent to one skilled in the art that various changes and modifications may be made therein without departing from the invention. The appended claims are intended to cover all such changes and modifications that fall within the true spirit and scope of the invention.

Claims

WHAT IS CLAIMED:

1. A compliant vascular graft for implantation in a blood vessel, the compliant vascular graft comprising: an inner graft layer comprising a tubular body defining a lumen that permits blood flow therethrough, the inner graft layer comprising a plurality of longitudinal pleats along a longitudinal axis of the tubular body to permit longitudinal expansion and a plurality of radial pleats to permit radial expansion; and an outer frame layer disposed outside the inner graft layer, wherein the inner graft layer and the outer frame layer are configured to transition from a longitudinally and radially contracted state to a longitudinally and radially expanded state via expansion of the plurality of longitudinal pleats and the plurality of radial pleats while implanted in the blood vessel.

2. The compliant vascular graft of claim 1 , wherein the outer frame layer compresses the inner graft layer circumferentially while allowing the inner graft layer to stretch longitudinally.

3. The compliant vascular graft of claim 1 or 2, wherein the outer frame layer allows the inner graft layer to bend and to twist without kinking.

4. The compliant vascular graft of any of the preceding claims, wherein at least a portion of the plurality of longitudinal pleats overlaps with the plurality of radial pleats.

5. The compliant vascular graft of any of the preceding claims, wherein the plurality of longitudinal pleats and the plurality of radial pleats extend along an entire length of the compliant vascular graft.

6. The compliant vascular graft of any of the preceding claims, wherein the inner graft layer has larger diameter than the outer frame layer.

7. The compliant vascular graft of any of the preceding claims, wherein the compliant vascular graft is configured to be implanted in a thoracic aorta or abdominal aorta.

8. The compliant vascular graft of any of the preceding claims, wherein the compliant vascular graft has radial and longitudinal compliance tailored to mimic compliance of a healthy thoracic aorta.

9. The compliant vascular graft of any of the preceding claims, wherein the compliant vascular graft transitions between the longitudinally and radially contracted state and the longitudinally and radially expanded state responsive to pressure changes in the blood vessel during the cardiac cycle to mimic compliance of a healthy aorta.

10. The compliant vascular graft of any of the preceding claims, wherein the outer frame layer comprises a plurality of rings.

11. The compliant vascular graft of claim 10, wherein each of the plurality of rings has a zigzag shape.

12. The compliant vascular graft of claim 10 or 11, wherein spacing between the plurality of rings increases from the longitudinally and radially contracted state to the longitudinally and radially expanded state.

13. The compliant vascular graft of any of claims 10-12, wherein the plurality of rings are not connected to one another.

14. The compliant vascular graft of any of claims 10-12, wherein the outer frame layer further comprises longitudinal struts that couple adjacent rings of the plurality of rings.

15. The compliant vascular graft of claim 14, wherein the longitudinal struts are straight or zigzag shaped.

16. The compliant vascular graft of any of the preceding claims, wherein the outer frame layer comprises a helical shape.

17. The compliant vascular graft of any of the preceding claims, wherein a majority of the outer frame layer is not coupled to inner graft layer.

18. The compliant vascular graft of any of the preceding claims, wherein the inner graft layer and the outer frame layer self-expand from the longitudinally and radially contracted state to the longitudinally and radially expanded state.

19. The compliant vascular graft of any of claims 1-17, wherein the inner graft layer and the outer frame layer are configured to be balloon expanded from the longitudinally and radially contracted state to the longitudinally and radially expanded state.

20. A method of using a compliant vascular graft for implantation in a blood vessel, the method comprising: selecting a compliant vascular graft comprising an inner graft layer and an outer frame layer disposed outside the inner graft layer, the inner graft layer comprising a tubular body defining a lumen that permits blood flow therethrough, the inner graft layer comprising a plurality of longitudinal pleats along a longitudinal axis of the tubular body to permit longitudinal expansion and a plurality of radial pleats to permit radial expansion; and implanting the compliant vascular graft in the blood vessel such that the inner graft layer and the outer frame layer transition from a longitudinally and radially contracted state to a longitudinally and radially expanded state via expansion of the plurality of longitudinal pleats and the plurality of radial pleats while implanted in the blood vessel.