Systems, devices, and methods for preventing autologous and xenograft failure.

Abstract

This concerns reinforced grafts designed to reduce postoperative maladjustment and failure. [Solution] The graft may be 3D printed and defined as a standard design or as a patient-specific external sheath customized to specific venous graft dimensions according to minimally invasive / non-invasive venous mapping and computational modeling. The external sheath contains one or more layers of various biomaterials to provide customized biomechanical properties. The external sheath is made to elute specific bioactive drugs, which also allows for pharmacological prevention of adverse remodeling in addition to mechanical support. These customizable features are tailored individually for each patient according to their specific medical history, including patient attributes.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 006,816, filed Apr. 8, 2020, the entire disclosure of which is incorporated herein by reference.

[0002] Description of Government Support This invention was made with government support under Contract HL123689 awarded by the National Institutes of Health. The U.S. government has certain rights in this invention.

[0003] Field of the Invention This disclosure relates to grafts, and more particularly to reinforced grafts designed to reduce postoperative discomfort and failure.

Background Art

[0004] Background Every year in the United States alone, approximately 400,000 coronary artery bypass grafts (CABG), 55,000 arteriovenous fistula creation procedures, and 20,000 peripheral artery bypass surgeries are performed. The rate of venous graft failure is high, at 50% after 10 years for CABG venous grafts and 25-55% after 5 years for bypass grafts below the knee joint. The primary failure rate for arteriovenous fistulas is approximately 40% at the end of the first year. The cost of fistula failure alone is estimated at $1.2 billion annually, and the cost of CABG venous graft failure is estimated to be even higher. Repeated procedures lead to increased complication and mortality rates, adding billions of dollars to the healthcare system's costs and reducing patients' quality of life. Graft failure costs billions of dollars annually to the healthcare system. While various approaches to improving grafts have been proposed, including those described in U.S. Patent Publications No. 9,265,632 (Patent Document 1); No. 9,579,224 (Patent Document 2); No. 2014 / 0303715 (Patent Document 3); No. 2012 / 0330437 (Patent Document 4); No. 8,361,101 (Patent Document 5); and No. 9,517,121 (Patent Document 6), these improvements have not yet fully addressed the significant problems of graft failure. Therefore, there is a need for improved graft structures that reduce postoperative maladjustment and thereby reduce or avoid graft failure. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] United States Patent Publication No. 9,265,632 [Patent Document 2] United States Patent Publication No. 9,579,224 [Patent Document 3] U.S. Patent Publication No. 2014 / 0303715 [Patent Document 4] U.S. Patent Publication No. 2012 / 0330437 [Patent Document 5] United States Patent Publication No. 8,361,101 [Patent Document 6] United States Patent Publication No. 9,517,121 [Overview of the project]

[0006] overview This disclosure relates to graft assembly and related methods, and more particularly to grafts with customized and / or adaptive reinforcement that mitigate maladjustment and failure of postoperative autologous and xenografts. In one aspect, the graft systems and methods described herein are advantageous for a variety of clinical applications, particularly coronary artery bypass surgery, peripheral artery disease, and arteriovenous fistulas. However, it should be recognized that these systems and methods may be applied to any graft application based on the concepts described herein.

[0007] Venous grafts are widely used in clinical applications including coronary artery bypass, peripheral artery bypass, and arteriovenous fistula. However, venous grafts have a very high failure rate, which increases healthcare spending by billions of dollars per year. The devices and methods proposed herein are designed to prevent vascular graft failure in general, and especially venous graft failure. In some embodiments, the method enables the production of a patient-specific, 3D-printed external sheath, custom-fabricated to the specific dimensions of the venous graft by the use of venous mapping and / or computational modeling. In some embodiments, the device may be manufactured in multiple sizes (e.g., diameter and / or length) and therefore may not be patient-specific or custom-made for an individual. In some embodiments, the sheath is monolayered. In other embodiments, the sheath is multilayered. The sheath may be formed by 3D printing. In some embodiments, the sheath may be formed from a polymer that is elastomeric and / or biodegradable. In some embodiments, the device is formed into a lattice design (e.g., with pores or openings), typically a lattice design that can be 3D printed. In some embodiments, the outer sheath comprises one or more layers of one or more biomaterials selected or customized to provide biomechanical properties suitable for a given patient. In some embodiments, the outer sheath has a braided structure. In some embodiments, the outer sheath may comprise one or more layers that, in addition to enhanced mechanical support, elute specific bioactive agents to enable pharmacological prevention of adverse remodeling. These customizable features may be individually tailored for each patient in accordance with patient-specific medical history, including hypertension, diabetes, smoking history, or any related patient attributes. In one aspect, the method described herein protects vascular grafts, particularly venous grafts, during direct exposure to arterial pressure, which can induce adverse remodeling and graft failure. The outer sheath protects venous grafts from over-inflation and adverse consequences resulting from damage when exposed to arterial pressure after implantation.The approach described herein enables graft design that supports precision medical solutions for cardiovascular bypass surgery.

[0008] Current surgical techniques offer little help in protecting vascular grafts (usually venous grafts) from maladaptation after implantation. In fact, the common intraoperative technique of inflating the graft before implantation may even worsen maladaptive responses. In the United States, nearly 500,000 patients with multivascular or diffuse coronary artery disease undergo coronary artery bypass grafting (CABG) each year. Surgeons have a choice between arterial or venous grafts, and while arterial grafts offer superior performance, their availability is limited. Therefore, venous grafts are used in approximately 95% of patients undergoing CABG. However, venous grafts experience occlusion and failure at a rate of 50% within 5 to 10 years post-surgery, and within 5 years of graft failure, 30% of patients experience repeat revascularization, myocardial infarction, or death. It is well known that adverse remodeling plays a major role in venous graft occlusion. This is partly due to the rapid change in biomechanical load when a vein is moved into the arterial circulation as a bypass graft and comes into direct contact with arterial blood pressure. Recent modeling and experimental work by our team of inventors has shown that gradually changing the mechanical load on a venous graft may allow for a more favorable adaptation to arterial pressure, thus potentially minimizing the risk of long-term graft failure. Therefore, the objective of the improved graft designs described herein is to reduce maladjustment and failure of autologous and xenografts after surgery. In some embodiments, these graft designs reduce graft maladjustment by utilizing custom-fit, blood-free devices made from biodegradable or bioabsorbable materials.

[0009] To actually achieve this, the graft assembly may utilize a single-layer or multi-layer, patient-specific, and 3D-printed sheath composed of a biocompatible, biodegradable, elastomerous, and / or drug-eluting biomaterial to act as an external support to prevent venous graft failure. The sheath may be customized for the patient or may be made in various sizes and shapes and then selected for a particular patient. Typically, the external support is blood-non-contact. As described herein, the external support or sheath that covers and is placed over the graft vascular system is referred to as the graft assembly or graft system. The graft systems described herein may be constructed from a variety of biomaterials, including hydrogels, whose composition may be carefully tuned to produce different biomechanical properties depending on the size, location, hemodynamic load, geometric shape, and cellular composition of the vascular graft. In some embodiments, the sheath is formed from a biodegradable material designed to maintain structural integrity for at least a short period after surgery (e.g., 1–6 weeks). In some embodiments, each layer of the multilayer sheath may be constructed using different biomaterials to induce stepwise degradation. In some embodiments, the outer support may be constructed to elute specific agents that promote endothelial health, inhibit processes of harmful remodeling, reduce hyperproliferative cell proliferation and matrix production, stimulate angiogenesis in local tissues, or achieve other molecular and cellular benefits.

[0010] In some embodiments, the external support has varying biodegradability of the sheath layer at different lumen diameters, thereby providing different stages of limiting over-dilation, adaptability to graft pathway twisting and profiling, and the ability to specifically size the sheath for each individual venous graft based on sheath design and preoperative imaging. In addition, the incorporation of drugs, immunomodulators, or inflammatory modulators may further aid in the optimal arterialization of the venous conduit. [Brief explanation of the drawing]

[0011] [Figure 1] Figures 1A and 1B show side cross-sectional views of single-layer and multi-layer graft assemblies based on several embodiments of the present invention. [Figure 2] This document describes a manufacturing method for forming an external support using clinical imaging techniques, based on several embodiments. [Figure 3] A method for manufacturing an exemplary external support having a braided external support, based on several embodiments, is shown. [Figure 4] A method for implanting a graft assembly having a braided external support, based on several embodiments, is described. [Figure 5] Figures 5A to 5B show external graft supports with grid designs based on several embodiments. [Figure 6A] A method for implanting a graft assembly having an external support structure based on a grid design is described below. [Figure 6B] A method for implanting a graft assembly having an external support structure based on a grid design is described below. [Figure 6C] A method for implanting a graft assembly having an external support structure based on a grid design is described below. [Figure 6D] A method for implanting a graft assembly having an external support structure based on a grid design is described below. [Figure 6E] A method for implanting a graft assembly having an external support structure based on a grid design is described below. [Modes for carrying out the invention]

[0012] Description of the present invention In the United States, nearly 500,000 patients with multivascular or diffuse coronary artery disease undergo coronary artery bypass grafting (CABG) each year. Surgeons have the choice between arterial or venous grafts, and while arterial grafts offer superior performance, their availability is limited. Therefore, venous grafts are used in approximately 95% of patients undergoing CABG. However, venous grafts experience occlusion and failure at a rate of 50% within 5 to 10 years post-surgery, and within 5 years of graft failure, 30% of patients experience repeat revascularization procedures, myocardial infarction, or death. It is well known that adverse remodeling plays a major role in venous graft occlusion. This is thought to be partly due to the rapid change in biomechanical load when a vein is moved into the arterial circulation as a bypass graft and comes into direct contact with arterial blood pressure. Recent modeling and experimental efforts by our team and others have shown that gradually changing the mechanical load applied to a venous graft may allow for a more favorable adaptation to arterial pressure and flow, thus minimizing the risk of long-term graft failure. To actually achieve this, the graft assemblies described herein utilize an external support that provides a postoperative adaptive response to mitigate the aforementioned problems and avoid graft failure. In other embodiments, the external support may be made in various sizes, shapes, and properties and selected based on the specific patient's anatomical structure and needs. In some embodiments, the graft assembly utilizes a monolayer sheath that acts as an external adventitial support to prevent venous graft failure; the monolayer sheath may be 3D printed or designed as a wrap and composed of a biocompatible, biodegradable, and / or bioabsorbable elastomer biomaterial, and may have drug-eluting capabilities. Alternative techniques may include dip coating, electrospinning, extrusion molding, sheet wrapping, and salt leaching. In some embodiments, the external support is customized or designed to be patient-specific.In some embodiments, a plurality of outer sheaths are provided having various dimensions (e.g., diameter, length, shape) and / or various properties (e.g., strength, durability, biodegradability, drug elution), from which a clinician can select a suitable outer support for a graft assembly in a given patient based on the patient's anatomical structure or the needs required by a given procedure.

[0013] I. Graft Assembly In one aspect, the approach described herein presents a novel pathway for constructing an outer sheath for venous graft support that is cost-effective, patient-specific, and biodegradable. The geometry of the vein may be determined using minimally invasive / non-invasive mapping routinely performed on the patient prior to cardiovascular bypass surgery. Imaging data may be used with methods of image segmentation and anatomical model construction to build a virtual computer model of the outer sheath that precisely matches the design size and geometry of the graft used in the bypass surgery. It should be understood that the desired graft size and geometry may be different from that of the vein to which the graft is to be attached, and for example, an over-sized graft may be used. In some embodiments, each graft constructed in this process is custom designed for that patient. In some embodiments, the sheath is 3D printed to be available at the time of surgery. Optionally, 3D printing may be integrated into the normal clinical workflow.

[0014] For further customization of the sheath for each patient, different biomaterials can be used in a single-layer or multi-layer sheath design to provide optimal biomechanical properties (e.g., for hypertensive patients versus non-hypertensive patients); or specific drugs for elution can be loaded onto the sheath depending on the patient's medical history (e.g., for diabetic smokers versus non-diabetic non-smokers, or any combination of co-existing diseases). Next, the custom sheath is applied and fixed to the vein during CABG surgery (e.g., fixed by clips, tissue adhesives, sutures, natural juxtaposition, "tight fit", or any suitable fixing means). Using a custom 3D model of the vein is also thought to enable virtual surgery of CABG hemodynamics, or virtual remodeling and adaptation in a patient-specific model. These novel features assist in precision medicine solutions for cardiovascular bypass surgery.

[0015] In one aspect, the external support is selected or designed to match the properties of the vascular structure to which the graft is attached. In some embodiments, the structural stiffness of the external support (product of material stiffness and thickness) should match the structural stiffness of the adjacent vascular structure. The material stiffness of the material may be in the range of 1 MPa (megapascals) to 10 GPa (gigapascals), and this range includes the stiffness of bioabsorbable polymers such as PPF (poly(propylene fumurate)), PGS (poly(glycerol sebacate)), PCLA (polycaprolactone-co-lactide), PLA (polylactide), PLLA (poly(l-lactic acid)), PCL (polycaprolactone), and PGA (polyglycolide), polyvinylidene fluoride (PVDF), polyurethane (PU), polypropylene (PP), and PP, poly(ε-caprolactone) (PεCL), or any combination of these materials. These are common polymer materials used in grafts, and some embodiments of the grafts described herein may be formed from these polymers. In some embodiments, the outer support is generally tubular, with a length of 2 cm to 60 cm, typically 5 cm to 20 cm, e.g., within 10 to 12 cm, and a diameter of 0.1 cm to 3 cm, typically 0.1 cm to 2 cm, e.g., within 0.2 to 1 cm or 0.2 to 0.5 cm. In some embodiments, the thickness of the outer support may be in the range of 0.1 to 10 mm, typically about 0.2 to 1 mm. It should be noted that the outer support may be of any suitable dimensions selected to suit the patient's vascular structure or the requirements of the particular procedure. The outer support may have a size and modulus that maintains a uniform diameter and reduces turbulence within the venous segment of the graft in order to enable favorable hemodynamics.

[0016] In another aspect, as shown in the embodiments in Figures 1A-1B, for example, the graft assembly includes an external support comprising one or more layers. Figure 1A shows a graft assembly 10 having a vascular graft 10 with an external support 20 consisting of a single layer designed or selected to match design specifications corresponding to the characteristics of the vascular structure to which the graft is attached. The external component 20 may be formed of materials individually or in combination selected or customized to match the characteristics or design specifications of the natural vascular structure. In some embodiments, the external support comprises a biodegradable material to provide further reinforcement immediately after surgery and for a short period thereafter (e.g., 1-6 weeks post-surgery), and to dissolve when additional reinforcement is no longer needed, thereby providing properties similar to the existing vascular structure. In some embodiments, this short post-surgery period may be 1, 2, 3, 4, 5, or 6 weeks after surgery. In some embodiments, the external support is formed by braiding a biodegradable material, such as wire, sheet, or mesh, over the graft tube.

[0017] Figure 1B shows a graft assembly 101 having a graft tube outer support 10 composed of two layers 20 and 30. The layers may be formed of the same material or of different materials having different properties. In some embodiments, the layers provide different functions, such as increased rigidity and drug release. For example, layer 20 may provide reinforcement against expansion, and layer 30 may provide drug release. In some embodiments, one or more of the layers may be biodegradable and others non-biodegradable to provide variability in properties. In some embodiments, multilayer graft assemblies with different biodegradation rates are used to provide design properties that change or adapt over time, thereby reducing postoperative maladjustment and failure. It should be recognized that the layers and their associated functions can be arranged in any number of ways. Furthermore, it should be recognized that multilayer graft assemblies are not limited to two layers but can encompass any desired number of layers.

[0018] In some embodiments, the number of layers on the outer support ranges from one to one, typically from one to three layers. However, it should be noted that any number of multiple layers may be used, especially when microscale and nanoscale manufacturing methods are involved. In addition to providing structural reinforcement, one or more of the layers may be configured to provide specific functions, such as any of the following or any combination thereof: • To biodegrade over time and maintain mechanical integrity over a set period of time, such as any number of hours, days, weeks, or months (for example, not less than a short period, typically within 1 to 6 weeks after surgery). • Incorporate drugs including macrophage and TGFβ inhibitors, other anti-inflammatory modulators, and immune modulators to prevent excessive inflammation and enable the development of new tissue. The drugs prevent the formation of neointima-mediated lesions, inflammatory collagen, and atherosclerotic lesions. Drug release capacity may last for up to 12 months. • To prevent compressive stress on existing or newly formed tissue, the layer should be oversized relative to the vascular diameter at a given pressure (e.g., 10 mmHg). • Construct a multi-layer design to match the desired structural rigidity. The sheath design may be configured as follows: providing surgical handling ease while minimizing damage to the sheath or pre-existing tissue wall (e.g., a resilient lattice design for easier handling); and / or providing ease of integration into the clinical workflow in CABG surgery without disruption (e.g., being provided in a state that can be inserted into the workflow without requiring extensive modifications to the sheath or the clinical workflow).

[0019] In yet another aspect, one or more layers of the outer support may be constructed by various manufacturing approaches. In some embodiments, the outer support is formed by a braided or wrapped design, as described in the embodiments below. In some embodiments, one or more layers are constructed by additive manufacturing methods such as 3D printing. Suitable additive manufacturing apparatus and methods capable of producing objects, as known and described, for example, in U.S. Patent No. 5,236,637 of Hull, U.S. Patents No. 5,391,072 and 5,529,473 of Lawton, U.S. Patent No. 7,438,846 of John, U.S. Patent No. 7,892,474 of Shkolnik, U.S. Patent No. 8,110,135 of El-Siblani, U.S. Patent Publication No. 2013 / 0292862 of Joyce, and U.S. Patent Publication No. 2013 / 0295212 of Chen et al., include bottom-up and top-down additive manufacturing methods and apparatus. In some embodiments, the additive manufacturing stage is carried out by one of a group of bottom-up methods, sometimes called continuous liquid interface manufacturing (CLIP). CLIP is publicly known and is described, for example, in U.S. Patents 9,211,678, 9,205,601, 9,216,546, etc.; J. Tumbleston et al., Continuous liquid interface production of 3D Objects, Science 347, 1349-1352 (2015); and R. Janusziewcz et al., Layerless fabrication with continuous liquid interface production, Proc. Natl. Acad. Sci. USA 113, 11703-11708 (2016). Other techniques include stereolithography (SLA) and digital light processing (DLP). Both methods are based on the photopolymerization or photocrosslinking process, which remains the fastest 3D printing method, and exhibit high resolution compared to other techniques, as they are limited only by the printer's light source and pixilation (resolution).These and other such techniques can be further understood by referring to U.S. Patent No. 10,465,044, European Patent No. 3063205B1, and PCT Publication No. WO2020 / 014699A1. However, it should be recognized that these are examples of manufacturing techniques that may be used, and the formation of external supports and graft assemblies is not limited to these methods.

[0020] II. Method A. How to manufacture a customized graft assembly In some embodiments, the design of the external support may be customized for individual patients by image-based modeling. Figure 2 shows an exemplary manufacturing method 200 for forming the external support by utilizing clinical imaging techniques. Method 200 may include the following steps:

[0021] (Step 201) Before surgery, peripheral veins are imaged using non-invasive clinical imaging techniques that can be performed in a consultation room setting or in the operating room. In some embodiments, the imaging modality is ultrasound. Alternative imaging modalities may include CT scans (computed tomography scans) and MRI (magnetic resonance imaging).

[0022] (Step 202) Import the medical images into the computational software framework. In some embodiments, the intensity of the images may be adjusted and the images may be processed with filters.

[0023] (Step 203) Construct a 3D geometric shape by segmenting the lumen and lofting the segmentation. The computational framework enables segmentation of the lumen using 2D segmentation with loft, 3D segmentation, or machine learning methods, and as a result constructs a 3D model of the vascular geometric shape. The framework also enables manipulation of the 3D model.

[0024] (Step 204) The geometric shape of the external support is constructed by extruding the normals to the vein wall surface. Manipulation or optimization of the 3D external support model by computer-aided design or formal optimization methods is performed so that the design specifications of the external support are met. The design specifications may include the size, thickness, length, and layers in the graft, as well as additional material at the ends to enable or assist in the anastomosis.

[0025] (Step 205) Resize the geometric shape of the 3D external support to match the design specifications.

[0026] (Step 206) The outer support is manufactured using a preferred manufacturing technique or a hybrid of techniques. In some embodiments, the outer support is formed by 3D printing.

[0027] (Step 207) Optionally, combine with other manufacturing techniques and processes to match the design specifications. 3D printing may be further combined with alternative manufacturing techniques and additional processes to match the design specifications. Alternative techniques may include dip coating, electrospinning, extrusion molding, sheet wrapping, and salt leaching. Additional processes may include pharmacological seeding and nanoparticle embedding.

[0028] (Step 208) Sterilize and package the external support for use in the operating room.

[0029] (Stage 209) The fabricated external support is attached to and implanted on the graft vascular tissue during surgery. An example of this stage is shown in Figures 6A-6B.

[0030] The method described above is illustrative and may be modified as desired to exclude or modify one or more of the steps described above, or to include additional steps. While this method illustrates a specific modeling approach, the 3D geometry may be performed by any suitable modeling approach. In addition, various other manufacturing processes and techniques may be used as alternatives or additions to those described above.

[0031] B. Method for manufacturing a braided outer support. Some embodiments include braided designs with multiple layers in addition to the 3D printing described above. Figure 3 shows a method for manufacturing a braided external support, which may include the following steps: Step A shows a customized jig including a sterile vice, a mandrel 301, and strips of biodegradable mesh 302. In Step B, the mesh strips are braided on the mandrel with pitch and layers to match the design specifications. Next, in Steps C and D, the braided support is sutured 303 at multiple locations along its length to maintain morphological and structural integrity. It should be recognized that this is only one approach to forming an external support to create custom or adaptive graft external supports, and alternative and / or additional processes may be utilized.

[0032] C. Method for implanting and applying a graft assembly to a vein The present invention also includes a method for equipping and applying an adaptive graft onto a vein. For example, the sheath is equipped onto the vein using a 3D printed design or a braided design. The method may also include the following: A. To enable the sheath to be fitted over the vein without causing damage, the sheath diameter is expanded using a support device such as a microscope or rigid tube with one end tapered. B. Alternatively, or additionally, a temporary conduit, which may be disposable, may be inserted into the sheath to facilitate loading a vein into the sheath. C. Extensions such as skirts or flares added to the ends of the sheath allow for flexible anastomosis to the existing tissue. D. To select the sheath size in order to maintain the target size, venous pressurization (e.g., pressurization up to a physiological value of 5–10 mmHg) may be used. E. Compressing the sheath axially allows the inner diameter to be increased to facilitate loading. F. When the sheath is stretched axially, the inner diameter adjusts to achieve a proper fit.

[0033] D. Method for embedding a braided external support. The graft assembly may be attached to the vascular structure in a conventional manner, or it may be implanted according to a dedicated implantation method. Figure 4 shows an exemplary method for implanting a braided external support, which includes the following steps.

[0034] In step A, the external support 400 is formed on the internal tube 401 either beforehand or in the operating room. In this embodiment, the support 400 may be formed by a biodegradable braid (e.g., braided wire, sheet, or strip) as described above. The external support is intermittently stitched, sutured, bonded, or stapled along its length to improve structural integrity and maintain its shape. The internal tube is kept inside the device until step F. In some embodiments, this process requires only about 10-20 minutes of construction time, even when performed manually.

[0035] In stage B, the braided external support is sized to be slightly oversized in both the circumferential and axial directions compared to the excised vein at 10 mmHg.

[0036] In stage C, the proximal anastomosis is created and hemostasis is confirmed. Guide sutures (white arrows) are sutured to the distal end of the perivenous tissue, and the external support is attached.

[0037] In steps D and E, slide the external support over the guide suture and move it past the proximal anastomosis.

[0038] In step F, the internal tube 401 is pulled out to preliminarily verify the size of the external support.

[0039] In step G, create the distal anastomosis, degas the system, and confirm hemostasis. Stretch the external support to its final conformation, covering the distal anastomosis; release the clamps and fill the covered vein graft. Assess the juxtaposition of the external support and the vein graft and adjust the reinforcing layer (e.g., braid) of the external support to cover the entire length and surface area of ​​the vein. Securely fix the proximal and distal ends of the external support to the surrounding tissue if necessary.

[0040] Figures 5A and 5B illustrate another embodiment of the external support 500 for the graft system as described above. Figure 5A shows a side view of the external support 500, and Figure 5B shows a perspective view. In this embodiment, the external support 500 is a single-layer tubular support 510 formed of a suitable material (e.g., polymer, biodegradable material) and is defined as a lattice structure having openings 520 (e.g., pores or voids) inside the lattice design. In some embodiments, this design has sufficient strength to allow the external support to be placed during surgical procedures without a removable internal support tube, thereby increasing ease of handling without damaging the support wall or pre-existing tissue, and allowing for better integration into the clinical workflow.

[0041] Figures 6A–6D show the implantation of an external support 600 of the same design as that in Figures 5A–5B. As shown in Figure 6A, the external support 600 may initially be handled during the surgical procedure by a support rod 601 extending through it. A guide suture 602 is attached to a cardiovascular vessel C (e.g., an anastomosed vein) of the heart H. The guide suture 602 may be fed through the external support 600, for example, by using an internal rod 601 that is pulled back through the support 600. As shown in Figure 6B, the clinician may then advance the external support 600 over the cardiovascular vessel C through the guide wire 602. As shown in Figure 6C, the clinician continues to advance the external support 600 until it is fully positioned in the desired location over the cardiovascular vessel. As shown in Figure 6D, the guide suture 602 may be removed / pulled back. As shown in Figure 6E, the external support 600 may be securely fixed in place, for example, by dissolvable sutures, so that it remains in place for at least a short period after the surgical procedure, as described herein, to provide cardiovascular reinforcement.

[0042] While the present invention has been described in the above specification with reference to its specific aspects, it will be recognized by those skilled in the art that the invention is not limited thereto. The various features, aspects, and aspects of the invention described above may be used individually or in combination. Furthermore, the invention may be used in any number of environments and uses not limited thereto without departing from the broader spirit and scope of this specification. Accordingly, this specification and the accompanying drawings should be considered illustrative, not restrictive. It should be noted that the terms “comprising,” “including,” and “having” as used herein are specifically intended to be read as open-ended technical terms. Each of the references cited herein is incorporated herein by reference for all purposes.

Claims

1. An external support tube, configured to extend along the outside of the graft while allowing blood to pass through it; A lumen extending through the outer support, sized to facilitate the placement of the outer support tube over the graft, and It is equipped with, In order to mechanically reinforce the graft for at least a certain period after the surgical procedure, the body of the external support has dimensions and characteristics selected or designed to match and correspond to the graft or the specific vascular structure to which the graft is attached. External support for graft assemblies.

2. The external support according to claim 1, comprising a single layer of 3D printed design.

3. The external support according to claim 2, wherein the 3D printed design is a grid design having a plurality of openings therein.

4. An external support according to any one of claims 1 to 3, which is strong enough to be handled during surgical procedures even without an internal tubular support being placed inside.

5. An external support according to any one of claims 1 to 4, which is formed of a biodegradable material that maintains structural integrity for at least the period after a surgical procedure.

6. The external support according to any one of claims 1 to 5, wherein the period after the surgical procedure is 1 to 6 weeks.

7. It comprises one or more layers with different properties, These different properties include biodegradability, bioabsorbability, biointegration, porosity, rigidity, or any combination thereof. The external support according to claim 1.

8. The external support according to claim 1, comprising a braided piece of biodegradable material.

9. An external support according to any one of the claims, which is designed with structural rigidity that matches or exceeds that of a specific vascular structure to which the graft is attached.

10. A method for forming a graft assembly, comprising the following steps: A step of imaging candidate peripheral veins in the area where the graft assembly will be implanted, using a non-invasive / minimally invasive imaging method, wherein the graft assembly comprises a graft and an external support; The step of constructing a 3D model of the graft and the lumen of the external support of the graft assembly to be implanted; The step of adapting the 3D model to match design specifications which are either defined or determined in advance from the imaging of the peripheral veins; and The step of forming the external support of the graft assembly based on the adapted 3D model.

11. The method according to claim 10, wherein the step of forming an external support includes braiding pieces of biodegradable material to match the design specifications.

12. The method according to claim 10 or 11, wherein the design specifications include any of structural rigidity, thickness of an external support, diameter, or any combination thereof.

13. The method according to any one of claims 10 to 12, wherein the external support comprises one or more layers.

14. The method according to any one of claims 10 to 13, wherein forming the graft assembly includes 3D printing.

15. Forming a graft assembly involves utilizing one or more manufacturing processes to match the graft assembly to design specifications; The additional process includes any of the following: dip coating, electrospinning, extrusion molding, sheet wrapping, salt leaching, or any combination thereof. The method according to any one of claims 10 to 14.

16. A method for forming an external support for a graft assembly to provide reinforcement of graft vessels, comprising the following steps: A step of providing a 3D design for an external support having a tubular shape having dimensions suitable for covering and placing the grafted vascular system, wherein the design is standard or customized for a specific patient; and A step of forming the external support by 3D printing using a material having properties suitable for strengthening the grafted vessel, wherein the material is selected or customized to maintain structural integrity for at least a period of time after the grafting procedure.

17. The method according to claim 16, wherein the 3D design is a grid having a plurality of openings therein.

18. The method according to claim 16 or 17, wherein the 3D design is a single layer.

19. The method according to any one of claims 16 to 18, wherein the material is biodegradable and the period is within 1 to 6 weeks.

20. A method for implanting a graft assembly, comprising the following steps: The step of providing the graft assembly customized to match or exceed the design specifications corresponding to the vascular structure, The vascular structure is a vascular structure in which the graft assembly is fitted between the proximal and distal anastomoses, along the position of the excised vein. The graft assembly comprises a graft and an external support, The graft assembly is sized to be slightly oversized compared to the excised vein, both circumferentially and axially; The next step is to create the proximal anastomosis, then fix a guide suture to the distal end of the perivenous tissue and attach the external support to the vascular structure; The step of sliding the external support on the guide suture and moving the external support past the proximal anastomosis; This step involves fabricating the distal anastomosis, positioning the external support to reach the final conformational position covering the distal anastomosis, releasing any clamps restricting blood flow, and checking the placement of the external support.

21. This is the stage where the external support protects the graft from direct exposure to arterial pressure, thereby inhibiting harmful remodeling and graft failure after implantation. The method according to claim 20, further comprising:

22. The method according to claim 20 or 21, wherein the graft assembly is customized for the patient, and the method is performed within a cardiovascular bypass surgery.

23. The method according to any one of claims 20 to 22, wherein the external support comprises one or more layers.

24. The method according to any one of claims 20 to 23, wherein the graft assembly is formed at least partially by 3D printing.

25. A method for implanting a graft assembly, comprising the following steps: A step of providing an external graft support having dimensions and characteristics selected or customized to match or correspond to the graft vessel over which the external support is fitted; The step of attaching the guide suture to the graft vessel; Steps include feeding the guide suture through at least a portion of the external graft support; The step of advancing the external support onto the graft vessel to a desired position through the guide suture; The step of removing the guide suture; and A step of securely fixing the external support to the desired position of the grafted vessel, thereby reinforcing the grafted vessel with the external support for at least a period of time after the grafting procedure.

26. This is the stage where the external support protects the graft from direct exposure to arterial pressure, thereby inhibiting harmful remodeling and graft failure after implantation. The method according to claim 25, further comprising:

27. The method according to claim 25 or 26, wherein the external support comprises a single layer.

28. The method according to any one of claims 25 to 27, comprising 3D printing of an external support.

29. The method according to any one of claims 25 to 28, wherein the external support is a lattice design.

30. The method according to any one of claims 25 to 29, wherein the external support is formed of a biodegradable material that maintains structural integrity for at least a period of time within 1 to 6 weeks after the grafting procedure.

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