Asymmetric arteriovenous grafts, methods of making same, and uses thereof

Abstract

Asymmetric arteriovenous grafts (AAVs) and uses thereof. In various examples, an AAV comprises a first AAV graft portion (e.g., arterial anastomosis portion or arterial anastomosis portion end), a second AAV graft portion (e.g., a venous anastomosis portion or a venous anastomosis end), a third AAV graft portion (e.g., a transition portion, such as, for example, a tapered transition portion, or a transition zone, such as, for example, a tapered transition zone), where a wall thickness of the third AAV graft portion decreases along at least a portion of the length of the third AAV graft portion and / or an inner diameter of the third AAV graft portion increases along at least a portion of the length of the third AAV graft portion. In various examples, an AAV graft is a compliant AAV graft. In various examples, a dialysis method uses an AAV graft (e.g., as an arteriovenous shunt or the like).

Description

ASYMMETRIC ARTERIOVENOUS GRAFTS, METHODS OF MAKING SAME, AND USES THEREOFCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 526,855, filed July 14, 2023; the contents of the above-identified application are hereby fully incorporated herein by reference in their entirety.BACKGROUND OF THE DISCLOSURE

[0002] A hemocompatible surface remains elusive after decades of research. Dialysis is the only treatment option for over 97% of the end-stage renal disease (ESRD) patients who cannot get a transplant. Approximately 90% of these patients are on hemodialysis. Hemodialysis requires a high flow filtration system. Therefore, a hemocompatible material is desirable. When an implanted self-contained artificial kidney becomes a reality, then a relatively low flow system will be feasible. However, it will place even higher requirement on hemocompatibility and overall biocompatibility. Until such a device is available, addressing deficiencies of hemodialysis will significantly impact the care of ESRD patients.

[0003] Vascular access for hemodialysis, using either an arteriovenous (AV) fistula or AV graft is problematic because both access strategies have deficiencies. The AV fistula is the standard dialysis access and national guidelines on “fistula first” maximizes the number of patients who can dialyze through AV fistulae. However, approximately 39% of AV fistula fails to mature. For matured AV fistula, approximately 40% need interventions to maintain sufficient intra-access blood flow and 29% are abandoned within a year. This is because a fistula is an “abnormal connection between vessels or organs”. In the context of dialysis, connecting an artery directly to a vein induces a huge spike in pressure and turbulent flow, deforming the outflow vein and inflaming its cells. This mechanical overload drives the vein to thicken and adopt arterial like properties to satisfy the newly founded over-pressurized environment. This maturation process is usually successful in the setting of a healthy vein. A significant limitation in AV fistula creation is the availability of suitable veins. Because patients with ESRD often have numerous comorbidities and are elderly. The arm veins are often scarred from numerous prior punctures for blood draws and intravenous catheters. While AV fistulae are superior dialysis accesses, a large fraction of the ESRD population suffer from poor venous anatomy. Placement of AV fistula in the setting of poor veins typically results in multiple reinterventionsand abandoned accesses and this creates a huge financial and emotional burden on patients and increases costs for the healthcare system.

[0004] In the setting of poor veins, AV grafts are placed. The primary patency rate of grafts are 66% at one year, dropping to 40%, 27% and 18% after two, three and five years respectively. Current grafts are susceptible to stenosis, neointimal hyperplasia, thrombosis, and infection. This is because the AV graft typically has two source materials: synthetic polymer and blood vessels derived from human or bovine sources. AV grafts face even more challenges than the fistula. Most synthetic grafts used for AV access creation are made with expanded polytetrafluoroethylene (ePTFE). The elastic modulus of PTFE is approximately 500 MPa depending on preparation. The moduli of veins and arteries vary depending on location, but the general range is approximately 15 kPa to 3 MPa, 33,000 to 160 times softer than PTFE. The difference in stiffness between graft and vein is much larger than that between artery and vein. Moreover, synthetic AV grafts are typically thick and tough to handle repeated cannulation. In contrast, a vein is thin and soft. The difference in thickness compounds the already stiff graft and further increases the compliance mismatch. Endothelial coverage on PTFE is very limited. The three-fold challenge of huge compliance mismatch, thrombogenicity and turbulent flow often leads to graft failure. In grafts derived from preserved human vessels or fixed decellularized animal vessels, the mismatch of mechanical properties of artery and vein persists: the graft can approximate one compliance or the other, but not both. Typically, the source of the preserved vessels are arteries, so the mismatch at the venous end persists. Further potential limitations of allografts include poor long-term patency and allosensitization that can impact the patient’s ability to receive a renal transplant. This same immune response can also result in graft inflammation and scarring over time. The xenografts are decellularized and do not have the same immune sensitization but have been shown to have poor primary patency (30% at 1 year), worse than that seen with PTFE (43% at 1 year), and similar infection rates. It only outperforms PTFE in secondary patency.

[0005] When AV fistulae mature, their long-term patency is superior. However, up to 25- 40% never mature due to poor venous anatomy or poor arterial flows and a significant number of patients are not candidates due to inadequate vein conduit. AV grafts have a lower immediate failure rate but long-term patency is inferior and require multiple interventions to maintainpatency due predominantly to the thrombogenicity of the graft material and the compliance mismatch at the venous anastomoses.

[0006] Vascular grafts started with Dacron® in the late 1950s. Studies on classic vascular grafts (Dacron® and PTFE) suggest that patients would remodel synthetic grafts with their own cells. Host remodeling was largely fibrotic with small amount of host tissue in the interstices of the Dacron graft and occasional partial endothelialization of the lumen. Existing synthetic vascular grafts are challenged by limited cell infiltration and fibrosis. This pathological remodeling does not improve its mechanical properties and contribute to thrombogenicity.

[0007] Humacyte® vascular grafts evolved from cell-laden constructs to decellularized tissue engineered grafts. These decellularized grafts undergo significant host remodeling after implantation leading to a useful conduit. However, the presence of cells in the graft was unnecessary for positive host remodeling. Cell sourcing, seeding, and culturing prolong and complicate graft fabrication, rendered it difficult to store and transport, and drastically increased the cost. Furthermore, the dense matrix of the decellularized graft hindered host cell infiltration, which takes 18 weeks to become significant.

[0008] Hemodialysis patients desire a vascular access that can be used immediately and is durable.SUMMARY OF THE DISCLOSURE

[0009] The present disclosure provides, inter alia. asymmetric arteriovenous (AAV) grafts and the like. The present disclosure also provides methods of making and using the AAV grafts.

[0010] In an aspect, the present disclosure provides AAV grafts. In various examples, an “AAV graft” describes a tubular member that acts as an artificial vessel or artificial vessels. In various examples, an AAV graft comprises a venous zone, a transition zone, and an arterial zone. In various examples, the AAV graft comprises a first end (e.g., a venous end) or a first orifice (e.g., a venous orifice) in the venous zone and a first end (e.g., an arterial end) or a first orifice (e.g., an arterial orifice) in the arterial zone. In various examples, an AAV graft comprises a transition zone between the first and second ends or orifices. In various examples, an AAV graft comprises gradually decreasing diameter accompanied by increasing wall thickness moving along the transition zone from the first to the second end or orifice. In various examples, the AAV graft comprises a first end (e.g., an arterial end) comprising a first orifice, a second end (e.g., a venous end) comprising a second orifice, and a transition zone (e.g., a tapered transitionend or the like) disposed between (e.g., in contact with or the like) the first end of the graft and the second end of the graft. In various examples, the transition zone begins at about a position at about 1 to about 66% of the total length of the graft from the first end of the graft and / or the transition zone ends at about a position at about 67 to about 99% of the total length of the graft from the first end of the graft. In various examples, an AAV graft comprises a first AAV graft portion; a second AAV graft portion, and a third graft portion. In various examples, the first graft portion comprises about 1 to about 66 percent (%) of a total length of the AAV graft and / or the second AAV graft portion comprising about 1 to about 33% of a total length of the AAV graft, the third AAV graft portion comprising about 1 to about 98% of the total length of the AAV graft and / or the third AAV graft portion is disposed between the first AAV graft portion and second AAV graft portion. In various examples, a wall thickness of the transition zone or the third AAV graft portion decreases along at least a portion, substantially all, or all of a length of the third AAV graft portion and / or an inner diameter of the third AAV graft portion increases along at least a portion, substantially all, or all of a length of the third AAV graft portion or the transition zone.

[0011] In an aspect, the present disclosure provides uses of asymmetric arteriovenous (AAV) grafts of the present disclosure. In various examples, an AAV graft is used in a dialysis method, such as, for example, a hemodialysis method or the like, or the like. In various examples, a hemodialysis method comprises implanting an AAV graft in an individual and subsequently carrying out hemodialysis on the individual. In various examples, a dialysis method comprises implantation of AAV graft (which is an arteriovenous shunt) or cannulation at the first AAV graft potion or first end of the AAV graft, or both.

[0012] In an aspect, the present disclosure provides kits. In various examples, a kit comprises one or more asymmetric arteriovenous (AAV) graft(s) of the present disclosure. In various examples, the kit includes a closed or sealed package that comprises the AAV graft or AAV grafts. In various examples, the package comprises one or more closed or sealed vials, bottles, blister (bubble) packs, or any other suitable packaging for the sale, distribution, or use of the AAV graft(s). In various examples, the kit includes a label describing the contents of the kit and providing instructions regarding use of the contents of the kit to treat an individual.

[0013] A goal of the present disclosure was to produce AAV grafts that remodel to an autologous structure and approximates or matches in different portions of an AAV graft thecompliance of a vein of an individual (e.g., the venous end of the AAV graft) and an artery of an individual (e.g., the arterial end of the graft) and transitions between these two compliance regimes. This approach is expected to achieve the long-term patency of successful AV fistulae without the limitations of existing synthetic grafts (e.g., restenosis, infection, and the like) and / or allografts / xenografts (e.g., immunosensitization, infection, and the like).BRIEF DESCRIPTION OF THE FIGURES

[0014] For a fuller understanding of the nature and objects of the disclosure, reference should be made to the following detailed description taken in conjunction with the accompanying figures.

[0015] FIG. 1 shows in vivo transformation of an elastic biodegradable graft specifically designed for hemodialysis access. The arterial end gradually transitions to the venous end with an increase in diameter and decrease in wall thickness. The compliance of the venous end is designed to match that of the native vein.

[0016] FIG. 2 shows a graft designed for the specific demand of hemodialysis access considering the inherent differences of arteries and veins. Differences of the thickness and diameter of the two ends can be programmed.

[0017] FIG. 3 shows solution electrowriting enabled control of fiber winding angle, spacing, and diameter. (A) Top row SEM: left and middle, rat-sized graft; right, sheep-sized. Inset: Multihead spinneret reduces the production time while maintaining the high reproducibility (arrow points to individual fibers emerging from the tip of each spinneret). Top row: Fiber Winding Angle (co); scale bars: 500 pm. Middle row: Fiber spacing; alter ‘pore size’; scale bars: 1 mm (inset scale bars: 30 pm). Bottom row: Fiber Diameter; scale bars: 2 pm. (B) Idealized architecture of an artery.

[0018] FIG. 4 shows (A) SEM images showing whole mount view of rings of the prototype from FIG. 4B at various locations of the graft (top). Optical micrographs focusing on the top of the ring reveal differences in wall thickness (bottom). (B) A prototype of an AAV graft having a transition zone illustrated in FIG. 2. X is the location on the graft. (C) The plot shows the change in diameter and wall thickness along the longitudinal axis. A tapered mandrel was used to provide the AAV graft.

[0019] FIG. 5 shows transformation of PGS-PCL grafts in Lewis rat aorta. (A) H&E staining of the graft transformation over time. Initial inflammation is largely resolved by 1 month. Scalebars top = 250 pm, bottom = 50 pm. (*) Top clipped while removing vena cava. (B) staining of vascular extracellular matrix molecules (Verhoeff for elastin, Masson’s trichrome for collagen, and Safranin-0 for glycosaminoglycan) at day 90. Scale bars = 50 pm. Insets show grafts at day 0 and 365, where black sutures marked anastomoses. Staining of age-matched native aorta provided for comparison.

[0020] FIG. 6 shows PGS-PCL vs. vein Graft in Sprague Dawley carotid. PGS-PCL: synthetic graft, Vein: vein graft, Carotid: native common carotid artery. (A) Gross appearance of the grafts at day 0 and 90 post-implantation. Arrows mark sutures. (B) Representative ultrasound images of grafts and native artery at day 90. B-mode (top), color Doppler and pulse wave modes (bottom). Arrows mark suture lines. (C) Survival plot showing the overall patency of the grafts. There is no statistical difference between two grafts. P = 0.15, log-rank test. (D) Representative images for immunofluorescence staining with the monocyte recruitment marker CCR2. Arrows mark CCR2+cells. L, lumen. (E) Quantification of CCR2 staining. (F) The area ratio of iNOS+to CD206+cells representing the M1 / M2 macrophage ratio. Data in (E) and (F) are means ± SD ( / ? = 4). *P < 0.05, Student’s / -test.

[0021] FIG. 7 shows a biaxial inflation device used with a multiphoton microscope to image collagen fibers of grafts retrieved at day 90 (left). Planar images were obtained starting from the outer wall, moving down to the inner wall with images stacked to obtain projection images of collagen fibers across the thickness of the sample. Scale bars: 100 pm. Note the difference in collagen fiber density, morphology, and orientation between samples (right). Remodeled PGS- PCL grafts and carotid artery show collagen fiber recruitment, as evidenced by orientation changes upon loading, consistent with the collagen fibers being load bearing. In contrast, collagen fibers in the “arterialized” vein grafts are more disorganized and show no recruitment upon loading.

[0022] FIG. 8 shows sheep carotid interposition model. (A) Graft immediately after unclamping and hemostasis. Inset: B-mode and color Doppler image of graft at 15-day postimplantation. (B) Transverse H&E sections of graft explanted at 15 day. 4X view. Tears in inner and outer surfaces are cryosectioning artifacts. Graft material is marked by dotted lines. Scale bar: 500 pm. (C) 10X view. Closer examination of the wall, highlighting concentrations of inflammatory cells at the margins of the material. Graft material marked by dotted lines. Solid arrowheads point out some of many capillaries infiltrating the graft material. The perfusion isassociated with inflammation, simultaneously it accelerates host cell infiltration and integration of the synthetic graft with the host. Scale bar: 100 gm.

[0023] FIG. 9 shows a schematic of an AAV graft design.

[0024] FIG. 10 shows an image of an extruded tapered graft. In this example, one end (a first end) has an inner diameter of 3.4 mm and the opposite end (a second end) inner diameter is 5.0 mm.

[0025] FIG. 11 shows an image of an extruded tapered graft.

[0026] FIG. 12 shows examples of combinations of the lengths of the three AAV graft portions or zones. Proportions between portions or zones are shown as arterial :transition:venous.

[0027] FIG. 13 shows examples of combinations of the lengths of the three AAV graft portions or zones (arterial:transition:venous).

[0028] FIG. 14 shows schematics of AAV graft designs.DETAILED DESCRIPTION OF THE DISCLOSURE

[0029] Although claimed subject matter will be described in terms of certain examples, other examples, including examples that do not provide all of the benefits and features set forth herein, are also within the scope of this disclosure. Various structural, logical, and process step changes may be made without departing from the scope of the disclosure.

[0030] As used herein, unless otherwise indicated, “about”, “substantially”, or “the like”, when used in connection with a measurable variable (such as, for example, a parameter, an amount, a temporal duration, or the like) or a list of alternatives, is meant to encompass variations of and from the specified value including, but not limited to, those within experimental error (which can be determined by, e.g., a given data set, an art accepted standard, etc. and / or with, e.g., a given confidence interval (e g. 90%, 95%, or more confidence interval from the mean), such as, for example, variations of + / -10% or less, + / -5% or less, + / -!% or less, and + / - 0.1% or less of and from the specified value), insofar such variations in a variable and / or variations in the alternatives are appropriate to perform in the instant disclosure. As used herein, the term “about” may mean that the amount or value in question is the exact value or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, it is understood that amounts, sizes, compositions, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error, or the like, orother factors known to those of skill in the art such that equivalent results or effects are obtained. In general, an amount, size, composition, parameter, or other quantity or characteristic, or alternative is “about” or “the like,” whether or not expressly stated to be such. It is understood that where “about,” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise.

[0031] Ranges of values are disclosed herein. The ranges set out a lower limit value and an upper limit value. Unless otherwise stated, the ranges include the lower limit value, the upper limit value, and all values between the lower limit value and the upper limit value, including, but not limited to, all values to the magnitude of the smallest value (either the lower limit value or the upper limit value) of a range. It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a numerical range of “0.1% to 5%” should be interpreted to include not only the explicitly recited values of 0.1% to 5%, but also, unless otherwise stated, include individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.5% to 1.1%; 0.5% to 2.4%; 0.5% to 3.2%, and 0.5% to 4.4%, and other possible sub-ranges) within the indicated range. It is also understood (as presented above) that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about, it will be understood that the particular value forms a further disclosure. For example, if the value “about 10” is disclosed, then “10” is also disclosed.

[0032] As used herein, unless otherwise stated, the term “group” refers to a chemical entity that is monovalent (i.e., has one terminus that can be covalently bonded to other chemical species), divalent, or polyvalent (i.e., has two or more termini that can be covalently bonded to other chemical species). The term “group” also includes radicals (e.g., monovalent and multivalent, such as, for example, divalent radicals, trivalent radicals, and the like). Illustrative, non-limiting examples of groups include:the like.

[0033] As used herein, unless otherwise stated, the term “structural analog” refers to any compound or polymer that can be envisioned to arise from an original compound or polymer if one atom or group of atoms, functional groups, or substructures is replaced with another atom or group of atoms, functional groups, substructures, or the like. In various examples, the term “structural analog” refers to any group that is derived from an original any compound or polymer by a chemical reaction, where the compound or polymer is modified or partially substituted such that at least one structural feature or substantially all of the compound or polymer or group is retained.

[0034] As used herein, unless otherwise stated, the term “biodegradable polymer” describes a polymer that can be cleaved either enzymatically or hydrolytically to break it down sufficiently so as to allow the body to absorb or clear it away. In various examples, a biodegradable graft is a graft in which at least a significant portion (e.g., at least 50%) of the graft degrades within one year of implantation.

[0035] As used herein, unless otherwise stated, the terms “coating”, “coatings”, “coated” and “coat” are forms of the same term defining material and process for making a material where a first substance or substrate surface is at least partially covered or associated with a second substance. Both the first and second substance are not required to be different. Further, when a surface is “coated” as used herein, unless otherwise stated, the coating may be effectuated by any chemical or mechanical bond or force, including linking agents. The “coating” need not be complete or cover the entire surface of the first substance to be “coated”. The “coating” may be complete as well (e.g., approximately covering the entire first substance). There can be multiple coatings and multiple substances within each coating. The coating may vary in thickness, or the coating thickness may be substantially uniform. Coatings contemplated in accordance with the present disclosure include, but are not limited to, medicated coatings, drug-eluting coatings, drugs or other compounds, pharmaceutically acceptable carriers, or the like, or any combination thereof, or any other organic, inorganic or organic / inorganic hybrid materials or the like. In various examples, the coating is a thromboresistant coating which has anticoagulant properties, such as, for example, heparin or the like, or any combination thereof.

[0036] As used herein, unless otherwise stated, the term “aligned” or “aligned fibers” describes a set of elements (e.g., fibers or the like) that have a substantially parallel or parallel arrangement along one or more axial direction(s).

[0037] As used herein, unless otherwise stated, the term “thermo-reactive” refers to materials that react (e.g., denature, degrade, crosslink, or otherwise change, or any combination thereof) at a specified temperature. Non-limiting examples of thermo-reactive materials include thermosetting materials, and thermo-degradable polymers (e.g., polymers which undergo thermal depolymerization, chain scission, removal of polymer side groups, polymer oxidation, or the like, or any combination thereof). Non-limiting examples of thermo-reactive materials include proteins, growth factors and cytokines: vascular endothelial growth factors (VEGF), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), epidermal growth factor (EGF), fibroblast growth factors (FGF), transforming growth factors (TGF-pi, TGF-[32, TGF-[33), interleukins (IL-1-17), ephrins, colony stimulating factors (CSF), bone morphogenic proteins (BMP), neurotrophin-3 (NT-3), platelet derived growth factor (PDGF), and the like, and any combination thereof. Non-limiting examples of thermo-reactive additives (e.g., thermo- degradable additives, or the like) include pharmaceutical compounds and temperature indicators. Non-limiting examples of thermo-reactive pharmaceutical compounds include rapamycin, tamoxifen, acetaminophen, ibuprofen, diclofenac, paclitaxel, amoxicillin, gentamicin, doxorubicin, cyclodextrin, naproxen, indomethacin, ketoprofen, metronidazole, ciprofloxacin, curcumin, insulin, lovastatin, and other drugs used as antimicrobials, anti-inflammatory agents, antineoplastics, statins, and the like, and any combination thereof. Non-limiting examples of thermo-reactive additives include indicators and the like, and any combination thereof. Nonlimiting examples of thermo-reactive indicators include fluorescein isothiocyanate (FITC), rhodamine b, and the like and any combination thereof.

[0038] The present disclosure provides, inter alia, asymmetric arteriovenous grafts. The present disclosure also provides methods of making and using asymmetric arteriovenous grafts.

[0039] In an aspect, the present disclosure provides asymmetric arteriovenous (AAV) grafts. In various examples, an AAV graft comprises (or is) an autologous structure. In various examples, an AAV graft is made by a method of the present disclosure. Non-limiting examples of AAV grafts are described herein.

[0040] In various examples, an AAV graft or a portion or end thereof comprises one or more tubular shape(s) (e.g., three distinct tubular shapes) or the like. In various examples, an “AAV graft” describes a tubular member that acts as an artificial vessel or artificial vessels. In various examples, a first AAV graft portion 12 or first AAV graft end (such as, for example, an arterial portion (e.g., an arterial anastomosis portion or the like), an arterial end (e.g., an arterial anastomosis end or the like), or the like), a second AAV graft portion 14 or second AAV graft end (such as, for example, a venous portion (e.g., an venous anastomosis portion or the like), a venous end (e.g., a venous anastomosis end or the like), and a transition portion 16 or transition zone (e.g., a tapered transition portion or the like, a tapered transition zone or the like, a third portion, or the like) are configured to be (or are in) fluid contact with one or more or all of the other portions. Non-limiting examples of AAV grafts are shown in FIG. 12 and 13.

[0041] FIGS. 9 and 14 shows various examples of an AAV graft. In various examples, the AAV graft comprises (or is made from) one or more elastomer(s), which may independently comprise a modulus of about 0.1 to about 100 MPa, including all 0.1 MPa values and ranges therebetween (e.g., about 0.2 to about 10 MPa or about 0.4 to about 3 MPa). The grafts comprise three zones, where at least a portion of the AAV graft may form a transition (which may be a smooth transition or the like) from thicker wall and smaller inner diameter (ID) arterial end (e.g., first end) to a thinner wall, larger ID venous end (e.g., second end). In various examples, the ID of the artery end (e.g., first end) is about 3 to about 10 mm, including all 0.1 mm values and ranges therebetween (e.g., about 4 to about 8 mm or about 5 to about 7 mm); the ID of the venous end (e.g., second end) is about 4 to about 12 mm, including all 0.1 mm values and ranges therebetween (e.g., about 5 to about 10 mm, or about 6 to about 9 mm). In various examples, the artery end (e.g., first end) wall thickness is about 0.4 to about 2 mm, including all 0.1 mm values and ranges therebetween (e.g., about 0.5 to about 1.8 mm or about 0.7 to about 1.2 mm); the venous end (e.g., second end) wall thickness is about 0. 1 to about 1 mm, including all 0.1 mm values and ranges therebetween (e.g., about 0.2 to about 0.8 mm or about 0.2 to about 0.4 mm). In various examples, the porosity of the AAV graft is about 30 to about 99% (based on the total volume of the AAV graft or end thereof), including all 0.1% values and ranges therebetween (e.g., 40 to about 99%, about 50 to about 90% or about 60 to about 80%). The arterial end (e.g., first end) may be less porous than venous end (e.g., second end). In various examples, the arterial end (e.g., first end) porosity is about 40 to about 90%, including all 0.1% values and rangestherebetween (e.g., about 50 to about 70% or about 60 to about 70%) and / or the venous end (e.g., second end) porosity is about 40 to about 99%, including all 0.1% values and ranges therebetween (e.g., about 60 to about 90% or about70 to about 90%). In various examples, the pore size (which may be average pore size) of the arterial end (e.g., first end) and / or the venous end (e.g., second end) is independently about 10 to about 200 microns, including all 0.1 micron values and ranges therebetween (e.g., about 20 to about 100 microns or about 25 to about 70 microns). The transition zone includes a decrease (which may be gradual and / or linear) in wall thickness and a gradual increase in inner diameter (which may be gradual and / or linear) moving from the end or a position proximal to the end of the transition zone disposed on the arterial end of the AAV graft to the end or a position proximal to the end of the transition zone disposed on the venous end of the AAV graft. In various examples, assuming the beginning of the arterial end (first end) is 0 and end of the venous end (e.g., second end) is 100%, the taper transition zone starts at about 30 to about 80% (e.g., about 40 to about 70% or about 50 to about 60%), the taper ends at about 70 to about 99% (e.g., about 80 to about 99% or about 90 to about 99%). In various other examples, assuming the beginning of the arterial end (e.g., first end) is 0 and the end of the venous end (e.g., second end) is 100%, the taper transition zone starts at about 1 to about 66% (e.g., about 5 to about 20%, or about 5%, the taper ends at about 2 to about 99% (e.g., about 67 to about 90% or about 70%).

[0042] In various examples, an AAV graft comprises a venous zone, a transition zone, and an arterial zone. In various examples, the AAV graft comprises a first end (e.g., a venous end) or a first orifice (e.g., a venous orifice) in the venous zone and a first end (e.g., an arterial end) or a first orifice (e.g., an arterial orifice) in the arterial zone. In various examples, an AAV graft comprises a transition zone between the first and second ends or orifices. In various examples, an AAV graft comprises gradually decreasing diameter accompanied by increasing wall thickness moving along the transition zone from the first to the second end or orifice. In various examples, an AAV graft or a zone thereof comprises a single material, two or more materials (e.g., a blend of materials or the like), a weave (e.g., a weave of fibers or the like), a laminate structure, or a composite of two or more materials. In various examples, an AAV graft comprises a first end (e.g., an arterial end) comprising a first orifice, second end (e.g., a venous end) comprising a second orifice, and a transition zone (e.g., a tapered transition end or the like) disposed between (e.g., in contact with or the like) the first end of the graft and the second end of the graft. Invarious examples, the transition zone begins at about a position at about 1 to about 66% of the total length of the graft from the first end of the graft, including all 0.1% values and ranges therebetween (e.g., about 5 to about 20%, about 30 to about 80%, about 40 to about 70%, or about 50 to about 60%) and / or the transition zone ends at about a position at about 67 to about 99% of the total length of the graft from the first end of the graft, including all 0.1% values and ranges therebetween (e.g., about 67 to about 95%, about 95 to about 99, about 95%, about 96%, about 97%, about 98%, or about 99%).

[0043] In various examples, an AAV graft comprises a first graft portion (e.g., arterial anastomosis portion or arterial anastomosis portion end) and a first orifice, a second graft portion (e.g., a venous anastomosis portion or a venous anastomosis end) and a second orifice, a third graft portion (e.g., a transition portion, such as, for example, a tapered transition portion or the like or a transition zone, such as, for example, a tapered transition zone or the like), where the third graft portion is disposed between the first graft portion and third graft portion. In various examples, a first graft portion (e.g., arterial anastomosis portion or arterial anastomosis portion end) comprises about 1 to about 66%, including all 0.1% values and ranges therebetween (e.g., about 5 to about 20%, about 30 to about 80%) of the total length of the graft), and / or a second graft portion (e.g., a venous anastomosis portion or a venous anastomosis end) comprises about 1 to about 33% of the total length of the graft, including all 0.1% values and ranges therebetween (e.g., about 1 to about 5 or about 5 to about 33%), and / or a third graft portion (e.g., a transition portion, such as, for example, a tapered transition portion or the like or a transition zone, such as, for example, a tapered transition zone or the like) comprises about 1 to about 98% of the total length of the graft, including all 0.1% values and ranges therebetween (e.g., about 15 to about 69% or about 47 to about 90%). In various examples, the percentages (such as, for example, the aforementioned percentages) of the first graft portion, second graft portion, and third graft portion equal 100%. In various examples, a first AAV graft portion 12 (e.g., arterial anastomosis portion or arterial anastomosis portion end) comprises about 5% of the total length of the AAV graft and a first orifice, a second AAV graft portion 14 (e.g., a venous anastomosis portion or a venous anastomosis end) comprises about 30% of the total length of the AAV graft and a second orifice, a third AAV graft portion 16 (e.g., a transition portion, such as, for example, a tapered transition portion or the like or a transition zone, such as, for example, a tapered transition zone or the like) comprises about 65% of the total length of the AAV graft.

[0044] In various examples, a first AAV graft portion 12, a second AAV graft portion 14, and a third AAV graft portion 16 are aligned along or with (e.g., coaxially or the like) a longitudinal axis of the AAV graft. In various examples, a first AAV graft portion 12, a second AAV graft portion 14, and a third AAV graft portion 16 each comprise two orifices (each orifice disposed at or forming a terminus of the respective AAV graft portion). In various examples, a first AAV graft portion 12 and a second AAV graft portion 14 are fluidically connected with (e.g., define a fluid channel or the like with) a third AAV graft portion 16 (or all of the AAV graft portions are fluidly connected) via the orifices of a first AAV graft portion 12, a second AAV graft portion 14, and a third AAV graft portion 16.

[0045] In various examples, an AAV graft comprises the following percentages of first AAV graft portion 12 (e.g., arterial anastomosis portion or arterial anastomosis portion end), third AAV graft portion 16 (e.g., a transition portion, such as, for example, a tapered transition portion or the like or a transition zone, such as, for example, a tapered transition zone or the like), and second AAV graft portion 14 (e.g., a venous anastomosis portion or a venous anastomosis end) (based on the total (e.g., 100%) AAV graft length): about 5 to about 10%, about 60 to about 65%, and about 30 to about 33%; about 5%, about 62%, and about 33%; about 5%, about 65%, and about 30%; about 5%, about 90%, and about 5%; about 5%, about 94%, and about 1%; about 10%, about 60%, and about 30%; about 10%, about 80%, and about 10%; about 10%, about 95%, and about 5%; about 20%, about 60%, and about 20%; about 20%, about 70%, and about 10%; about 20%, about 75%, and about 5%; about 25%, about 65%, and about 10%; about 30%, about 40%, and about 30%; about 30%, about 50%, about 20%; about 30%, about 60%, and about 10%; about 30, about 65%, about 5%; about 40%, about 30%, about 30%; about 40%, about 40%, and about 20%; about 40%, about 50%, and about 10%; or about 40%, about 55%, and about 5%.

[0046] In various examples, an AAV graft or a portion or end thereof (such as, for example, one or more layer(s) of an AAV graft or a portion or end thereof) mimic and / or correspond to one or more artery structures and / or venous structures of an individual. In various examples, an AAV graft or a portion or end thereof (such as, for example, one or more layer(s) of an AAV graft or a portion or end thereof) mimic and / or correspond to one or more artery structures shown in FIG. 3B.

[0047] An AAV graft or a portion or end thereof can have various and / or varying cross- sectional wall dimensions (e.g., wall thicknesses or the like) and / or cross-sectional dimensions of an inner volume defined by a wall of the AAV graft (e.g., an inner diameter or the like). In various examples, a cross-sectional wall dimension (e.g., wall thickness or the like) and / or a cross-sectional dimension of an inner volume defined by a wall of the AAV graft (e.g., an inner diameter or the like) of the first AAV graft portion 12 and / or the second graft portion 14 varies or is substantially the same or the same along the length of the individual portion. Typically, a first end or first AAV graft portion 12 comprises a thicker wall and / or a smaller diameter than a second end or second AAV graft portion 14.

[0048] In various examples, a first AAV graft portion 12 (e.g., arterial anastomosis portion or arterial anastomosis portion end) comprises at least one cross-sectional wall dimension (e.g., wall thickness or the like) of about 0.4 millimeters (mm) to about 2 mm, including all 0.05 mm values and ranges therebetween (e.g., about 0.5 mm to about 1.8 mm, about 0.7 mm to about 1.2 mm, about 0.8 mm to about 2 mm or about 1 mm) and / or a second AAV graft portion 14 (e.g., venous anastomosis portion or venous anastomosis portion end) comprises at least one cross- sectional wall dimension (e.g., wall thickness or the like) of about 100 microns (0.1 mm) to about 1 mm, including all 0.01 or 0.05 mm values and ranges therebetween (e.g., about 0.2 mm to about 0.8 mm, about 0.2 mm to about 0.4 mm, or about 0.2 mm or about 0.3mm) and / or a first AAV graft portion 12 (e.g., arterial anastomosis portion or arterial anastomosis portion end) comprises at least one a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (e.g., an inner diameter or the like) of about 3 mm to about 10 mm, including all 0.1 mm values and ranges therebetween (e.g., about 4 mm to about 8 mm, about 5 mm to about 7 mm) and / or a second AAV graft portion 14 (e.g., venous anastomosis portion or venous anastomosis portion end) comprises at least one a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (e.g., an inner diameter or the like) of about 4 mm to about 12 mm, including all 0.1 mm values and ranges therebetween (e.g., about 5 mm to about 10 mm, about 6 mm to about 9 mm).

[0049] In various examples, at least one cross-sectional dimension of a wall (e.g., wall thickness or the like) of the third AAV graft portion 16 disposed on (or proximate to or in contact with) the wall of the first AAV graft portion 12 is independently about ± 5% (e.g., ± 4%, ± 3%, ± 2%, ± 1%) of (e.g., about the same as) a cross-sectional dimension of a wall (e.g., wall thicknessor the like) of the first AAV graft portion 12 and / or at least one cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of the third AAV graft portion 16 is independently about ± 5% (e.g., ± 4%, ± 3%, ± 2%, ± 1%) of (e.g., about the same as) a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of the first AAV graft portion 12 and / or at least one cross-sectional dimension of a wall (e.g., wall thickness or the like) of the third AAV graft portion 16 disposed on (or proximate to or in contact with) the wall of the second AAV graft portion 14 is independently about ± 5% of (e.g., about the same as) a cross-sectional dimension of a wall (e.g., wall thickness or the like) of the first AAV graft portion 12 and / or at least one cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of the third AAV graft portion 16 is independently about ± 5% (e.g., ± 4%, ± 3%, ± 2%, ± 1%) of (e.g., about the same as) a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of the second AAV graft portion 14.

[0050] In various examples, an AAV graft comprises an inner diameter of from about 3 to about 20 mm, including all 0.01 mm values and ranges therebetween (e.g., about 4 mm to about 12 mm), at an end (which may be a second end, venous end or wide end) to about 2 to about 10 mm, including all 0.01 mm values and ranges therebetween (e g., about 3 mm to about 10 mm), at the other end (which may a second end, opposite end, arterial end, or a narrow end) of the graft. In various examples, an AAV graft includes two orifices. In various examples, an AAV graft includes a second orifice (e.g., a venous orifice) and a first orifice (e.g., an arterial orifice). In various examples, the wall thickness of the second orifice (e.g., venous orifice) is about 0.05 to about 4 mm, including all 0.01 mm values and ranges therebetween (e.g., from about 0.05 to about 3 mm or about 0.1 to about 1 mm), and / or the wall thickness of the first orifice (e.g., arterial orifice) is about 0.2 to about 5 mm, including all 0.01 mm values and ranges therebetween (e.g., from about 0.4 to about 2 mm). The second orifice (e.g., venous orifice) may be configured to be fluidly connected with a vein of an individual. The first orifice (e.g., arterial orifice) may be configured to be fluidly connected with an artery of an individual.

[0051] In various examples, an AAV graft is used to connect a vein and an artery. In various examples, an AAV graft is used for hemodialysis access. In various examples, an AAV graftaccommodates the size “mismatch” between arteries and veins (arteries are typically smaller in diameter but with a thicker wall) for both conduit diameter and wall thickness. In various examples, an AAV graft comprises a second end (which may be a venous portion or end) that is wider (e.g., has a larger inner diameter) and / or is thinner (e.g., has a thinner wall thickness) than a first portion or end (which may be an arterial portion or end). Without intending to be bound by any particular theory, it is considered that the difference in hardness and / or stiffness results from the second portion or end (which may be a venous portion or end) being wider and / or thinner than the first portion or end (which may be an arterial portion or end). Arteries and veins also have different composition and organization, further contributing to the difference in biomechanics. In various examples, an AAV graft comprises a tapered inner diameter.

[0052] In various examples, the ratio of a second portion or end (e.g., venous portion or end) inner diameter to a first portion or end (e.g., arterial portion or end) inner diameter is about 1.5:1 to about 10: 1, including all 0.1 values and ranges therebetween (e g., from about 1.5: 1 to about 8: 1), and / or the ratio of second portion or end (e.g., venous portion or end) wall thickness to first portion or end wall thickness is about 1 : 1.25 to about 1 : 100, including all 0.1 values and ranges therebetween (e.g., about 1 :4 to about 1 : 10). In various examples, the first end (which may be an arterial end) of the AAV graft is harder or tougher and / or stiffer than the second end (which may be a venous end).

[0053] In various examples, an inner linear dimension of the second end and / or orifice (e g., venous orifice), which may be an inner diameter of the second end and / or orifice or the like, is about 10% to about 1000% larger (e.g., from about 10% to about 200% larger), including all 0.1 % values and ranges therebetween) than an inner linear dimension of the first end and / or orifice (e.g., arterial orifice), which may be an inner diameter of the second end and / or orifice. In various examples, a linear dimension of the second end and / or orifice (e.g., venous orifice), which may be a wall thickness of the second end and / or orifice, is about 5% to about 10,000% smaller (e.g., including all 0.1 % values and ranges therebetween) than a linear dimension of the first end and / or orifice (e.g., arterial orifice), which may be a wall thickness of the first end and / or orifice.

[0054] A dimension or dimensions of an AAV graft or portion or end thereof (such as, for example, cross-sectional wall dimension(s) (e.g., cross-sectional dimension(s) (such as, for example, wall thickness(s) or the like), cross-sectional dimension(s) of an inner volume of theAAV graft defined by the wall of the AAV graft (e.g., an inner diameter or the like), pore size, porosity, or the like) can be determined by methods known in the art. In various examples, a dimension or dimensions (such as, for example, wall thickness(s) or the like), cross-sectional dimension(s) of an inner volume of the AAV graft defined by the wall of the AAV graft or portion or end thereof (e.g., an inner diameter or the like of an AAV graft or portion or end thereof or the like) is / are determined by one or more physical measurement(s) (such as, for example, caliper measurement, conical aperture gauge, or the like), one or more microscopy method(s) (such as, for example, optical microscopy, or the like, or any combination thereof), or the like or any combination thereof. In various examples, pore size and / or porosity of an AAV graft or portion or end thereof are determined by one or more physical measurement(s) (such as, for example, gravimetric analysis or the like), one more microscopy method(s) (such as, for example, optical microscopy, electron microscopy, computer tomography (CT), or the like, or any combination thereof) or the like or any combination thereof.

[0055] An AAV graft can comprise various transition portions (such as, for example, tapered transition portions, transition zones (e.g., tapered transition zones or the like), third AAV graft portions 16, or the like). In various examples, a transition portion is the bulk (e.g., greater than 50%) of the AAV graft. In various examples, a transition portion comprises a decreasing gradient of a cross-sectional wall dimension (e.g., wall thickness or the like) and / or an increasing gradient of a cross-sectional dimension of an inner volume defined by a wall of the transition portion (e.g., an inner diameter or the like) along a length of the transition portion. In various other examples, a cross-sectional dimension (e.g., wall thickness or the like) of a transition portion decreases along at least a portion of the length of the transition portion and / or a cross-sectional dimension of an inner volume defined by a wall of the transition portion (e.g., an inner diameter or the like) of the transition portion increases along at least a portion of the length of the transition portion.

[0056] In various examples, a transition portion (such as, for example, a tapered transition portion or the like, a transition zone (e.g., a tapered transition zone or the like), a third AAV graft portion 16, or the like) begins at about a position at about 10 to about 80% of the total length of the AAV graft from the first end or portion of the AAV graft, including all 0.1% values and ranges therebetween (e.g., about 20%) and / or the transition portion ends at about a position at about 80 to about 99% (e.g., about 95 to about 99%) of the total length of the AAV graft fromthe first end or portion of the AAV graft, including all 0.1% values and ranges therebetween (e.g., about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, or about 99%). In various examples, a transition portion is or provides a transition zone connecting the two portions (ends), gradually changing (e.g., with no abrupt change or step function change of) the compliance, the diameter, or the wall thickness, or any combination thereof.

[0057] In various examples, a first orifice and a second orifice of a transition portion (such as, for example, a tapered transition portion or the like), a transition zone (e.g., a tapered transition zone or the like), a third AAV graft portion 16, or the like) each comprises an inner linear cross-sectional dimension (such as, for example, a diameter or the like) and each orifice comprises an inner linear cross-sectional dimension (such as, for example, a diameter or the like) and, in various example, the ratio of first orifice inner linear cross-sectional dimension (such as, for example, a diameter or the like) to second orifice inner linear cross-sectional dimension (such as, for example, a diameter or the like) is about 1.5:1 to about 10: 1, including all 0.1 ratio values and ranges therebetween, and / or the ratio of first orifice wall thickness to second orifice wall thickness is about 1 : 1.25 to about 1 : 100, including all 0.1 ratio values and ranges therebetween.

[0058] In various examples, a transition portion (such as, for example, a tapered transition portion or the like), a transition zone (e.g., a tapered transition zone or the like), a third AAV graft portion 16, or the like) comprises a first end disposed on (or proximate to or in contact with) the first AAV graft portion 12 and the first portion comprises a first cross-sectional dimension (e.g., wall thickness or the like), and the transition portion comprises a second end portion disposed on (or proximate to or in contact with) the second AAV graft portion 14 and the second end portion comprises a second cross-sectional dimension (e.g., wall thickness or the like). In various examples, the cross-sectional dimension (e.g., wall thickness or the like) thickness and / or the cross-sectional dimensions of an inner volume defined by a wall of the AAV graft (e.g., an inner diameter or the like) of a transition portion substantially matches or matches the arterial end (e.g., first end or portion) wall thickness at one end and the venous end (e.g., second end or portion) at the other end and changes (e.g., increases or decreases) at least a portion, substantially all, or all of the length of the transition zone. In various examples, the first cross-sectional dimension of the first end portion of the transition portion is greater than the second cross-sectional dimension of the second end portion of the transition portion. In various examples, a first orifice comprises an inner linear cross-sectional dimension (such as, forexample, a diameter or the like) that is about 10% to about 1000% larger than an inner linear cross-sectional dimension (such as, for example, a diameter or the like) of the second orifice.

[0059] In various examples, a transition portion (such as, for example, a tapered transition portion or the like), a transition zone (e.g., a tapered transition zone or the like), a third AAV graft portion 16, or the like) comprises a gradient in wall thickness (e.g., a decreasing gradient) and / or inner diameter (e.g., an increasing gradient) moving (e.g., along a linear axis) from the a first end (e.g., an arterial end) to the second end (e.g., a venous end). In various examples, the gradient(s) is / are independently, defined by or is a substantially linear function (such as, for example, a linear function), a step function, or the like. In various examples, the gradient of wall thickness decreases over at least a portion, substantially all, or all of the transition zone is 0.0007 mm / mm to 0.0034 mm / mm, including all 0.00005 mm / mm values and ranges therebetween.

[0060] In various examples, a change in a cross-sectional dimension (e.g., wall thickness or the like) of a transition portion (such as, for example, a tapered transition portion or the like), a transition zone (e.g., a tapered transition zone or the like), a third AAV graft portion 16, or the like) corresponds to (or is) a decreasing function (e.g., taper or the like) moving from a first AAV graft end or portion to a second AAV graft end portion or a first end to a second end of the transition portion. In various examples, the decreasing function is a smooth decreasing function or the like. In various examples, the decreasing function is a linear decreasing function (such as, for example, a decreasing smooth linear function or the like) or the like and / or a change in a cross-sectional dimension of an inner volume (e.g., lumen) of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of a transition portion corresponds to or is a increasing function (e.g., taper or the like) moving from a first AAV graft end or portion to a second AAV graft end portion or a first end to a second end of the transition portion. In various examples, the increasing function is a smooth function or the like. In various examples, the increasing function is a linear function (such as, for example, a decreasing smooth linear function or the like) or the like.

[0061] An AAV graft or a portion or an end thereof can have a layered structure. In various examples, at least a portion or all of the AAV graft (e.g., first AAV graft portion 12 or end, second AAV graft portion 14 or end, or transition portion, or the like, or any combination thereof) comprises one or more layer(s). In various examples, at least a portion or all of the AAV graft (e.g., first AAV graft portion 12 or end, second AAV graft portion 14 or end, or transitionportion, or the like, or any combination thereof) comprises or is a single layer structure or a multilayer structure, or the like.

[0062] In various examples, an AAV graft or a portion or an end thereof (or one or more or all layers of an AAV graft or a portion or an end thereof) comprises one or more polymer(s), one or more foam(s) (which may independently comprise one or more polymer(s)), or the like. In various examples, AAV graft or a portion or an end thereof (or one or more or all layers of an AAV graft or a portion or an end thereof or a tube of an AAV graft or a portion or an end thereof) comprises a porous or non-porous polymer or polymers (which may independently be in the form of one or more layer(s)), a foam (which may independently be in the form of one or more layer(s)), or any combination thereof.

[0063] In various examples, an AAV graft or a portion or end thereof (or one or more or all layers of an AAV graft or a portion or end thereof) comprises a porous foam layer or tube and one or more non-porous layers (which may be configured (e.g., disposed on or proximate to an external surface of the AAV graft or the like). Without intending to be bound by any particular theory, it is considered such an AAV graft mitigates or prevents leakage from the AAV graft.

[0064] In various examples, an AAV graft or a portion or an end thereof (or one or more or all layers of an AAV graft or a portion or end thereof) comprises a plurality of fibers. In various examples, the fibers independently comprise a diameter (or an average inner diameter) of from about 0.1 micron to about 300 microns, including all 0.1 nm values and ranges therebetween (e.g., about 100 nm to about 300 microns). In various examples, at least a portion or substantially all (e.g., all) of an AAV graft or a portion or end thereof does not comprise a plurality of polymer fibers.

[0065] In various examples, an AAV graft or a portion or an end thereof comprises one or more layer(s) of fibers. A layer can comprise various fibers. In various examples, an AAV graft or a portion or end thereof comprises comprises one or more electrowritten layer(s) comprising fibers. In various examples, all of the layers of an AAV graft or a portion or end thereof are the same. In various examples, at least one portion of a layer and / or at least one layer comprises fibers that have at least one feature (e.g., structural feature, geometrical feature, compositional feature, or the like) that is different than the fibers of the other portion(s) of the fibers in a layer or other fibers in a layer.

[0066] In various examples, a fiber is a microfiber. In various examples, an AAV graft or a portion or an end thereof comprises three or more layer(s) of fibers. In various examples, the fibers are arranged in a predetermined pattern; the average diameter of the fibers is about 100 nm to about 500 microns, including all integer nm values and ranges therebetween; and an AAV graft or a portion or end thereof comprises a desired fiber fusion and / or fiber stacking. In various examples, the average diameter of the fibers is about 200 microns to at least 500 microns.

[0067] In various examples, a layer is a region of continuous fiber or groups of continuous fibers traversing the perimeter of an AAV graft or a portion or end thereof and the length of the AAV graft or the portion or the end thereof. In various other examples, a layer is a region of continuous fiber or groups of continuous fibers in an AAV graft or a portion or end thereof at a substantially constant distance from the inner wall of an AAV graft or a portion or end thereof. In various examples, a layer is further defined by structural and / or compositional features including, but not limited to, fiber angle, degree of fiber fusion, degree of fiber stacking, degree of porosity, average pore width, shape of pores, fiber diameter, conduit wall thickness, fiber material(s), fiber additive(s), and the like, and any combination thereof. In various examples, a static layer comprises substantially the same or the same structural and / or compositional features along the length an AAV graft or a portion or end thereof. In various examples, a dynamic layer comprises variable structural and / or compositional features along the length of an AAV graft or a portion or end thereof. A dynamic layer may have two or more distinct regions along the length of an AAV graft or a portion or end thereof, each having substantially different structural and / or compositional features. The two or more distinct regions may vary continuously along the longitudinal axis of an AAV graft or a portion or end thereof.

[0068] In various examples, an AAV graft or a portion or end thereof comprises comprises (or is) a hybrid structure. In various examples, an AAV graft or a portion or end thereof comprises is a multilayered AAV graft comprising a hybrid structure (at least two different layers, each layer comprising one or more different material(s)). In various examples, all of the layers are formed using the same method. In various examples, at least two layers are formed using different methods. In various examples, a layer comprises one or more polymer(s). In various examples, a layer comprises a plurality of fibers. In various examples, a layer does not comprise a fiber or a plurality of fibers.

[0069] In various examples, an AAV graft or a portion or end thereof comprises a hybrid structure or the like comprising one or more layer(s), each layer independently comprising one or more porous elastomer(s) (e.g., at least a portion or all of which are porous biodegradable elastomer(s) or the like) (e.g., porous elastomer(s) independently comprise(s) one or more chelation crosslinked polymer(s) (e.g., an inner layer, a core or the like); and one or more layer(s) of fibers (e.g., electrowritten fibers, electrospun fibers, or the like, or any combination thereof) (e.g., an outer layer, a sheath or the like). In various examples, the fibers are arranged in a predetermined pattern. In various examples, the average diameter of the fibers is about 100 nm to about 500 microns, including all 0.1 nm values and ranges therebetween. In various examples, an AAV graft or a portion or end thereof comprises a desired fiber fusion and / or fiber stacking; or any combination thereof, and at least one of the layer(s) or one or more layer(s) are disposed on the layer comprising one or more porous elastomer(s) (e.g., at least a portion or all of which may be porous biodegradable elastomer(s) or the like) (e.g., porous elastomer(s) independently comprise(s) one or more chelation crosslinked polymer(s)).

[0070] In various examples, a hybrid structure comprises (or is) one or more electrowritten layer(s) (or electrospun layer(s)) (e.g., comprising a material or polymer(s) described herein) or the like) and one or more layer(s) formed using a different method (e.g., a conventional method, such as, as for example, a method described herein). In various examples, at least a portion or all of the one or more electrowritten layer(s) (or electrospun layer(s) or the like) (which may be referred to as a sheath) independently is / are at least partially or completely disposed (e.g., certain electrowritten layer(s) or electrospun layer(s) is / are in physical contact with or the like) on a layer or layers formed using a different method (which may be referred to as a core). In these examples, the independent electrowritten layer(s) (or electrospun layer(s) or the like) may be an exterior layer (such as, for example, a sheath or the like).

[0071] An AAV graft or a portion or end thereof, which may be a hybrid structure or the like, may comprise a core and a sheath. In various examples, a core is a layer formed by a method described herein (such as, for example, an electrospinning method or the like) and a sheath, which may at least partially, substantially, or completely surround the core. In various examples, the sheath is a microfibrous sheath or a nanofibrous sheath. In various examples, an AAV graft or a portion or end thereof comprises a biodegradable core. In various examples, an AAV graft or a portion or end thereof comprises a tubular core (which may be a biodegradablepolyester tubular core). It is contemplated that a disclosed AAV graft may include PGS or any biodegradable and / or biocompatible substance with similar degradation rates and elasticity of PGS. In various examples, an AAV graft or a portion or end thereof further comprises a sheath which surrounds the core (which may be an electrowritten (or electrospun or the like) biodegradable polyester tubular core). In various examples, the sheath is a biodegradable polyester electrowritten (or electrospun) sheath which surrounds the tubular core to prevent, inhibit or reduce bleeding from the graft. In various examples, an electrowritten (or electrospun or the like) sheath (e.g., a biodegradable polyester sheath or the like) electrospun sheath comprises PCL or a PCL like substance which is capable of forming a less leaky (compared to an AAV graft without a sheath) or substantially nonleaky (or nonleaky) sheath, which may be hydrophobic, around the biodegradable polyester electrospun sheath. In various examples, the sheath includes a hemostatic material such as, for example, gelatin or the like, or any combination thereof, which is capable of inducing hemostatis shortly after implantation.

[0072] Without intending to be bound by any particular theory, it may be desirable the inner layer (e.g., a porous elastomer or the like) degrades (e.g., biodegrades or the like) at faster (e.g., substantially faster) rate than the outer layer. In various examples, an inner layer (e.g., a porous elastomer or the like) degrades (e.g., biodegrades or the like) at faster (e.g., substantially faster) rate than the outer layer.

[0073] In various examples, an AAV graft or a portion or end thereof comprises various types and degrees of desired fiber fusion and / or fiber stacking. In various examples, the fibers comprise a plurality of fusion points between at least two or two or more intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber. In various examples, for at least one or more or all fusion points, the overlapped distance of the first fiber and the second fiber is less than about 15%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% of the diameter of the first fiber and / or second fiber. In various examples, the plurality of fusion points between adjacent intersected fibers is observed at an average frequency of from about 5% to about 99%, including all 0.1 % values and ranges therebetween (e.g., about 5 % to about 90%, or about 10% to about 60%, or at least about 5%, or at least about 7%, or at least about 10% , or at least about 15 %, or at least about 20%, or at least about 30%, or at most about 99 %, or at most about 90 %, or at most about 80%, or at most about 70 %, or at most about 60 %, or at mostabout 50%). In various examples, fibers in an AAV graft or a portion or end thereof comprises a plurality of fusion points between two intersected fibers such that for each fusion point (or late least one fusion point) a bottom surface of a first fiber sticks to a top surface of a second fiber with an overlapped distance of less than 10% (or less than 1 %, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1%) of the diameter of the first fiber and / or second fiber.

[0074] In various examples, for each axial direction of an AAV graft or a portion or end thereof, the adjacent fibers in different layers are aligned one over the other and are vertically stacked or vertically staggered. In various examples, the fibers have an average stacking height of at least about 10 microns, or at least about 20 microns, or at least about 30 microns, or at least about 40 microns, or at least about 50 microns, or at least about 60 microns, or at least about 70 microns, or at least about 80 microns, or at least about 90 microns, or at least about 100 microns, or at least about 150 microns, or at least about 200 microns, or at least about 250 microns.

[0075] In various examples, an AAV graft or a portion or end thereof comprises one or more fiber(s) arranged in various predetermined patterns. In various examples, an AAV graft or a portion or end thereof comprises one or more layer(s) each comprising one or more group(s) of fibers optionally aligned in one or more axial direction(s) of an AAV graft or a portion or end thereof within and / or between the layer(s). In various examples, the group(s) of fibers is / are uniaxially, biaxially, or multi-axially oriented within and / or between the layer(s). In various examples, each group of fibers has a substantially constant winding angle, relative to the longitudinal axis of an AAV graft or a portion or end thereof. In various examples, the substantially constant winding angle is about 1° to about 89°, including all 0.1° values and ranges therebetween, relative to the longitudinal axis of an AAV graft or a portion or end thereof. In various examples, an AAV graft or a portion or end thereof comprises two groups of aligned fibers aligned in two directions with a substantially constant winding angle from about 15° to about 90°, from about 25° to about 80° or more preferably from about 35° to about 75°, including all 0.1° values and ranges therebetween, relative to the longitudinal axis of the AAV graft or the portion or the end thereof.

[0076] In various examples, an AAV graft or a portion or end thereof comprises a plurality of layers (e.g., at least three layers) of (independently, uniaxially or biaxially or multi-axially oriented) fibers. In various examples, for each axis / orientation / direction, the adjacent fibers in individual (or different) layers are vertically stacked and aligned one over another and / or theadjacent fibers in the same layer are horizontally separated in a substantially constant distance (or space apart). In various examples, an AAV graft or a portion or end thereof comprises two groups of aligned fibers (biaxially aligned fibers) aligned in two directions with a substantially constant winding angle (e.g., where the winding angle is chosen from a range of about 15 degrees to about 90 degrees, including all 0.1 degree values and ranges therebetween (e.g., about 25 degrees to about 80 degrees or about 35 degrees to about 75 degrees).

[0077] In various examples, an AAV graft or a portion or end thereof comprises a plurality of fiber (e.g., at least three layers of fibers), each fiber comprising at least one polymer or a plurality of polymers (e.g., at least two polymers); and optionally an additive distributed in at least one fiber or at least one polymer; where the adjacent fibers in adjacent layers are staggered or vertically aligned one over another, and the adjacent fibers in the same layer are spaced from each other, optionally where the additive could be uniformly distributed in at least one fiber and / or encapsulated by the polymer(s) in at least one fiber. In various examples, the polymer(s) comprise biocompatible polymer(s) and / or biodegradable polymer(s) and / or biocompatible biodegradable polymer(s).) In various examples, the fibers are biaxially oriented and aligned in two directions. In various examples, an AAV graft or a portion or end thereof comprises at least three layers of biaxially oriented fibers, where for each axis / orientation / direction, the adjacent fibers in different layers are vertically staggered / stacked and aligned one over another; and the adjacent fibers in the same layer are horizontally separated in a distance to form a plurality of pores / holes / cavities in the AAV graft or the portion or the end thereof.

[0078] An AAV graft or a portion or end thereof may be at least partially or completely porous or non-porous. In various examples, at least a portion or substantially all (e.g., all) of an AAV graft or a portion or end thereof are porous. In various examples, an AAV graft or a portion or end thereof comprises a plurality of pores. In various examples, at least a portion of a wall or all of the wall(s) of an AAV graft or a portion or end thereof (or one or more layer(s) of an AAV graft or a portion or end thereof) comprise(s) a plurality of pores, holes, cavities, or the like, or any combination thereof. In various examples, an AAV graft or a portion or end thereof comprises an open porous structure and / or closed porous structure, which may include a plurality of polymer fibers. In various examples, an AAV graft or a portion or end thereof comprises one or more layer(s), which may, independently, comprise porous structures. Each layer, independently, may comprise one or more group(s) of fibers, which are optionally aligned in oneor more axial directi on(s) of the AAV graft or the portion or the end thereof within and / or between the layer(s). In various examples, for each axial direction of the AAV graft or the portion or the end thereof, the adjacent fibers in different layers are aligned one over the other and are vertically stacked or vertically staggered. In various examples, each layer comprises one or more group(s) of fibers optionally aligned in one or more axial directions of the product within and / or between the layer(s).

[0079] Pores of an AAV graft or a portion or an end thereof (or layer of an AAV graft or a portion or an end thereof) can have various sizes and / or shapes and / or pore structures. In various examples, the average size (e.g., cross-sectional dimension, such as, for example, a diameter or the like, or the like) of the pores, holes, cavities, or any combination thereof is larger than a size of a cell (e.g., at least about 1 micron, at least about 5 microns, at least about 10 microns, at least about 20 microns, at least about 30 microns, at least about 40 microns, at least about 50 microns, etc.). In various other examples, the pores of the AAV graft or the portion or the end thereof independently (or on average) comprise a cross-sectional dimension (e.g., a diameter or the like) of about 10 microns to about 200 microns, including all 0.1 micron values and ranges therebetween (e.g., about 20 microns to about 100 microns or about 25 to about 75 microns). In various examples, pores, holes, cavities, or the like are independently characterized by a cross- sectional shape in the form of a cube, a cuboid, a rhombohedron, a rhomboid, or the like. In various examples, the pores, holes, cavities, or the like, or any combination thereof comprise a closed structure or an interconnected structure, or any combination thereof. In various examples, about 1% to about 100%, including all 0.1 % values and ranges therebetween, of the pores, holes, cavities, or the like, or any combination thereof are interconnected. In various examples, at least about 75% of the pores, holes, cavities, or the like, or any combination thereof are interconnected. In various examples, at least about 85% of the pores, holes, cavities, or the like, or any combination thereof are interconnected. In various examples, at least 95% of the pores, holes, cavities, or the like, or any combination thereof are interconnected. In various examples, at least about 99% of the pores are interconnected.

[0080] An AAV graft or a portion or end thereof (or layer of an AAV graft or a portion or an end thereof) can have various degrees of porosity. In various examples, an AAV graft or a portion or end thereof (or layer of an AAV graft or a portion or end thereof) is about 30 to about 99% (based on the total volume of the AAV graft or the portion or the end thereof wall) porous,including all 0.1 % values and ranges therebetween (e.g., 40 to about 99%, about 50 to about 90% or about 50 to about 90%, about 50 to about 99% or about 60 to about 90%).

[0081] In various examples, a first AAV graft portion 12 or end comprises a first porosity and the second AAV graft portion 14 or end comprises a second porosity and the first porosity is greater than the second porosity. In various examples, the first porosity is about 40 to about 90% (based on the total volume of the AAV graft wall), including all 0.1 porosity% values and ranges therebetween (e.g., about 50 to about 70% or about 60 to about 90%) and / or the second porosity is about 40 to about 99% (based on the total volume of the AAV graft or the portion or the end thereof wall), including all 0.1 porosity% values and ranges therebetween (e.g., about 60 to about 90% or about 70 to about 90%).

[0082] In various examples, the pores of an AAV graft or a portion or end thereof (or a layer of an AAV graft or a portion or end thereof are defined by a plurality of fibers. In various examples, the pores are defined by a plurality of stacked fibers, a plurality of distributed fibers, or the like, or any combination thereof. For example, a pore may be defined by a fiber of a first layer, spaced apart by a first predetermined space or pitch from the same fiber, or another fiber, on the first layer, and the fiber of a second layer, spaced apart by a second predetermined space or pitch, which may be equal to or different than the first predetermined space or pitch, with same fiber, or another fiber, on the second layer, with the fiber(s) of the first layer and the fiber(s) of the second layer being arranged at an angle relative to one another between 0° to 90°. In another example, a pore may be defined by fiber(s) of a first plurality of layers, spaced apart by a first predetermined space or pitch (which could comprise a varying space or pitch across the first plurality of layers) from the same fiber(s), or other fiber(s), comprising the first plurality of layers, and the fiber(s) of a second plurality of layers, spaced apart by a second predetermined space or pitch, which may be equal to or different than the first predetermined space or pitch (which could comprise a varying space or pitch across the second plurality of layers), with same fiber, or another fiber, on the second plurality of layers, with the fiber(s) of the first plurality of layers and the fiber(s) of the second plurality of layers being arranged at an angle relative to one another between 0° to 90°.

[0083] In various examples, one or more pores are formed, by arrangement of fiber(s) across a thickness of an AAV graft or a portion or end thereof, to extend through an AAV graft or a portion or end thereof (e.g., from an outer diameter to an inner diameter of a cylindrical AAVgraft or portion thereof or the like) or to extend only partially through a thickness of an AAV graft or a portion or end thereof. In a substantially cylindrical AAV graft, for example, an axis of a pore may be described as extending from a first position (pi, (pi, zi) in a cylindrical coordinate system for an AAV graft or a portion or end thereof to a second position (p2, q>2, Z2) in the cylindrical coordinate system where pi, (pi and / or zi may be equal to, or different than, p2, q)2, Z2. Accordingly, in various examples, pores extend radially outwardly relative to a longitudinal axis of a substantially cylindrical an AAV graft or a portion or end thereof, whereas in various examples pores extend both outwardly relative to a longitudinal axis of a substantially cylindrical an AAV graft or a portion or end thereof and along the longitudinal axis and / or circumferentially.

[0084] In various examples, the average width of the pores is at least about one micron. In various examples, the average width of the pores is at least about 5 microns, at least about 10 microns, at least about 20 microns, at least about 30 microns, at least about 40 microns, or at least about 50 microns. In various examples, the pores have a cube shape, a cuboid shape, a rhombohedron shape, a rhomboid shape, or the like.

[0085] In various examples, an AAV graft or a portion or end thereof (e.g., a layer or layers thereof) comprises pores to facilitate cell infdtration, but pores are not necessarily required. In various examples, the pores (e.g., substantially all or all of the pores) are uniformly distributed. In various examples, the pores are non-uniformly distributed. In various examples, an AAV graft or a portion or end thereof does not include any pores. In various examples, a porous AAV graft comprises at least 75% pore interconnectivity, such as, for example, about 80% to about 90%, about 90% to about 98%, including 75%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.99% interconnectivity.

[0086] In various examples, at least a portion of or all of the AAV graft or portion or end thereof (e.g., first AAV graft portion 12 or end, second AAV graft portion 14 or end, or transition portion (e.g., third AAV graft portion 16 or the like), or the like, or any combination thereof) comprises one or more polymer(s) (such as, for example, one or more elastomer(s) or the like) or the like. At least a portion of or all the polymer(s) may be in the form of fibers.

[0087] In various examples, a polymer is a synthetic organic polymer, a natural organic polymer, or an inorganic polymer. In various examples, a polymer is a homopolymer, acopolymer (such as, for example, a block-copolymer, a random copolymer, alternate copolymer, and graft copolymer, and the like). Non-limiting examples of polymers, which may be elastomers, include polyesters, polyurethanes, polyethers, polyketals, polyimides, polyamides, polycarbonates, polyacrylates, polysaccharides, structural analogs thereof, and any combination thereof. In various examples, a polymer is a chelation cross-linked polymer or the like.

[0088] Non-limiting examples, of polymers, which may be elastomers, include polyglycolides or polyglycolic acids (PGAs), polylactic acids (PLAs), polycaprolactone (PCLs), polyhydroxy alkanoate (PHAs), poly hydroxybutyrate (PHBs), polyethylene adipates (PEAs), polybutylene succinates (PBSs), poly (3 -hydroxybutyrate-co-3 -hydroxy valerate) (PHBVs), polyethylene terephthalate (PETs), polybutylene terephthalate (PBTs), polyethylene glycol (PEGs), polytrimethylene terephthalates (PTTs), poly(glycerol-sebacate) (PGSs), palmitate functionalized poly(glycerol sebacate) (PGSPs), poly(styrene-block-isobutylene-block-styrene) (SIBS), poly(epsilon caprolactone) (PCL), polymethyl methacrylate (PMMA), chitosan, gelatin, cellulose, polydioxanone, or the like, structural analogs thereof, or any combination thereof. In various examples, the polymer(s) is / are chosen from: silk, gelatin, and a polysaccharide, such as, for example, cellulose, chitin, chitosan, hyaluronic acid, dextran, and alginate, and the like, and any combination thereof.

[0089] In various examples, an AAV graft or a portion or end thereof comprises one or more natural polymer(s). In various examples, the natural polymer(s) independently comprise one or more amino acid(s), peptide(s), denatured peptide(s) (such as, for example, a gelatin from denatured collagen, polypeptides, proteins, carbohydrates, lipids, nucleic acids, glycoproteins, minerals, lipoproteins, glycolipids, glycosaminoglycans, proteoglycans, and the like, and any combination thereof).

[0090] In various examples, an AAV graft or a portion or end thereof comprises at least one thermo-reactive polymer. In various examples, an AAV graft or a portion or end thereof comprises thermo-reactive polymer(s), which are independently thermo-reactive at a temperature of at least about 60 °C.

[0091] In various examples, an AAV graft or a portion or end thereof comprises at least one first polymer and at least one second polymer. In various examples, the at least one first polymer is PGSP and / or the at least one second polymer is polyethylene terephthalate (PET). In various examples, at least one fiber comprises at least one first polymer and at least one second polymerand / or at least one first fiber comprises at least one first polymer and at least one second fiber comprises at least one second polymer. In various examples, the at least one first polymer is PGSP and / or the at least one second polymer is polyethylene terephthalate (PET). In various examples, a polymer is or polymers are not a polymer or polymers than can be melt electrospun (e.g., electrospun to provide an AAV graft or a portion or end thereof).

[0092] In various examples, an AV graft or portion or end thereof (e.g., a layer or layers of an AAV graft or portion or end thereof) comprise(s) one or more chelation crosslinked polymer(s) or the like. In various examples, a layer or layers is / are a layer or layers comprising a material described in, a layer or layers described in, or a layer or layers made by a method described in, or any combination thereof, International Patent Application No.PCT / US2021 / 044230, filed August 2, 2021 and titled “Chelation Crosslinked Polymers, Methods of Making Same, and Uses Thereof’, the disclosure of which with regard to material (such as, for example, chelation crosslinked polymers and the like) and methods of making same and uses of same are incorporated herein by reference.

[0093] In various examples, a layer or layers (e.g., a core or the like) of an AAV graft or a portion or end thereof (e.g., a layer or layers of an AAV graft or portion or end thereof) comprises one or more elastomer(s) (such as, porous elastomer(s) (e.g., at least a portion or all of which may be porous biodegradable elastomer(s) or the like)) or the like. In various examples, a layer or layers (e.g., a core) comprise(s) one or more chelation crosslinked polymer(s) or the like. In various examples, the sheath comprises PCL fibers. In various examples, the core comprises porous elastomer (e.g., a porous biodegradable elastomer or the like) and the sheath comprises PCL fibers. AAV graft length is tunable. AAV graft length inner diameter and wall thickness are also tunable. Fiber thickness, fiber fusion, fiber stacking, and winding angle are also tunable and can be controlled by various parameters.

[0094] An AAV graft or a portion or end thereof (e.g., a layer or layers of an AAV graft or portion or end thereof) can comprise fiber(s) comprising various polymer(s). In various examples, the fiber(s) independently comprises one or more polymer(s) described herein. In various examples, each fiber comprises one or more polymers(s) which is / are thermo-reactive at a temperature of at least 60 °C. In various examples, the one or more material(s) is / are thermo- reactive at a temperature of at least 60 °C, at least 100 °C, at least 150 °C, at least 166 °C, at least 170 °C, at least 180 °C, at least 190 °C, at least 200 °C, at least 210 °C, at least 220 °C, at least230 °C, at least 240 °C, at least 250 °C, at least 260 °C, at least 270 °C, at least 280 °C, at least 290 °C, or at least 300 °C.

[0095] In various examples, an AAV graft or a portion or end thereof (or one or more or all the fibers of an AAV graft or a portion or end thereof) (e.g., a layer or layers of an AAV graft or portion or end thereof) comprise(s) at least one polymer or at least two polymers. In various examples, the weight ratio of the two polymers is about 1 :9 to about 9: 1, from about 1 :5 to 5: 1, from about 1 :4 to about 4:1, from about 1 :3 to about 3: 1, from about 1 :2 to about 2: 1, at least about 1 :99, about 1 :9, about 1 :8, about 1:7, about 1 :6, about 1 :5, about 1 :4, about 1 :3, about 1:2, or about 1 : 1, or at most about 99: 1, at most about 9: 1, about 8: 1, about 7: 1, about 6: 1, about 5: 1, about 4: 1, about 3:1, about 2: 1, or about 1 : 1, including, for each stated ratio, all integer weight ratio values and ranges therebetween.

[0096] In various examples, at least one polymer comprises a cured (e g., thermally cured, electromagnetic radiation cured, accelerated particle cured, or the like, or any combination thereof) polymer, or the like, or any combination thereof. In various examples, at least one polymer does not comprise a cured (e.g., thermally cured, electromagnetic radiation cured, accelerated particle cured, or the like, or any combination thereof) polymer, or the like, or any combination thereof. In various examples, at least a portion of or all of an AAV graft or portion or end thereof (e.g., first AAV graft portion 12 or end, second AAV graft portion 14 or end, or third AAV graft portion 16 or end, or the like, or any combination thereof) or a layer or layers, or a portion thereof, of an AAV graft or a portion or end thereof is crosslinked.

[0097] An AAV graft or one or more portion(s) thereof may be crosslinked (e.g., the polymer(s) of the AAV graft or portion(s) thereof are crosslinked. In various examples, at least one polymer or more comprises a crosslinked (e.g., thermally crosslinked, electromagnetic radiation crosslinked, accelerated particle crosslinked, or the like, or any combination thereof) polymer, hydrogel, or the like, or any combination thereof. In various examples, the at least one polymer does not comprise a crosslinked (e.g., thermally crosslinked, electromagnetic radiation crosslinked, accelerated particle crosslinked, or the like, or any combination thereof) polymer, hydrogel, or the like, or any combination thereof.

[0098] In various examples, about 2% to about 100%, including all 0.1% values and ranges therebetween (e.g., about 2% to about 40% or about 75 to about 100%), of an AAV graft or a portion or end or zone or the like is crosslinked. In various examples, about 10 to about 25% of afirst portion or end (e.g., an arterial portion or end) is crosslinked and / or about 5 to about 15% of a second portion or end (e.g., a venous portion or end) is crosslinked. In various examples, a first portion or end (e.g., an arterial portion or end) comprises a crosslinking density (the percentage of crosslinked polymer repeat units (based on the total number of polymer repeat units)) of about 0.1% to about 50%, including all 0.1% values and ranges therebetween (e.g., about 10% to about 40%) and / or a second portion or end (e.g., a venous portion or end) comprises a crosslinking density of about 0.001% to about 30%, including all 0.1% values and ranges therebetween (e.g., about 0.1% to about 20%) and / or a transition portion (e.g., a tapered transition portion or the like, a transition zone, such as, for example, a tapered transition zone, o the third portion, or the like) comprises a crosslinking density of about 0.001% to about 50%, including all 0.1% values and ranges therebetween (e.g., about 1% to about 40%). Without intending to be bound by any particular theory, it is considered that crosslinking density can be varied (e.g., or the length of an AAV graft or a portion or end thereof) to achieve a desired compliance.

[0099] In various examples, an AAV graft or a portion or end thereof (e.g., first AAV graft portion 12 or end, second AAV graft portion 14 or end, or third AAV graft portion 16 or end, or the like, or any combination thereof) comprises at least one biocompatible polymer (such as, for example, a biocompatible and / or biodegradable elastomer or the like) and / or biodegradable polymer or all the polymer(s) in the AAV graft are biocompatible polymer(s) and / or biodegradable polymers) (such as, for example, biocompatible and / or biodegradable elastomer(s) or the like).

[0100] In various examples, one or more of the polymer(s) is / are biocompatible polymer(s), biodegradable polymer(s), or the like, or any combination thereof. In various examples, an AAV graft or a portion or end thereof comprises at least two biodegradable polymers. In various examples, a first biodegradable polymer has a degradation rate of at least 50% of the polymer degraded in less than about one year, less than about 9 months, less than about 6 months, less than about 3 months in a physiological environment or a biological environment; and a second biodegradable polymer has a degradation rate of at most about 50% of the polymer degraded in more than about one year, more than about 1.5 years, more than about 2 years, more than about 2.5 years, or more than about 3 years in a physiological environment or a biological environment.

[0101] An AAV graft or at least a portion or an end thereof may be at least partially, substantially, or completely biocompatible and / or biodegradable. In various examples, at least a portion or substantially all (e.g., all) of an AAV graft or a portion or end thereof is biocompatible and / or biodegradable. In various examples, at least a portion or substantially all (e.g., all) of the AAV graft is biodegradable. In various examples, at least about 95 % of the AAV graft degrades within about 90 days (e.g., within about 90 days of implantation). In various examples, a AAV graft comprises one or more first polymer(s) (such as, for example, biocompatible and / or biodegradable polymer(s)) independently exhibiting a degradation rate of at least 50% of the polymer degraded in less than one year, less than 9 months, less than 6 months, less than 3 months in a physiological environment or a biological environment and / or one or more second polymer(s) (such as, for example, biocompatible and / or non-biodegradable polymer(s)) independently exhibiting a degradation rate of at most 50% of the polymer degraded in more than one year, more than 1.5 years, more than 2 years, more than 2.5 years, or more than 3 years in a physiological environment or a biological environment.

[0102] In various examples, an AAV graft or a portion or end thereof is biodegradable and / or biocompatible. In various examples, an AAV graft comprises PGS and / or one or more of the following polymers: polylactides (PL As), poly(lactide-co-glycolides) (PLGAs), poly(dioxanone), polyphosphazenes, polyphosphoesters (such as, poly [1,4- bis(hydroxyethyl)terephthalate-alt-ethyloxyphosphate]; poly[l,4-bis(hydroxyethyl)terephthalate- alt-ethyloxyphosphate]-co-l,4-bis(hydroxyethyl)terephthalate-co-terephthalate; poly[(lactide-co- ethylene glycol)-co-ethyloxyphosphate]); polycaprolactone; poly(urethanes), polyglycolides (PGA) polyanhydrides, and polyorthoesters or any other similar synthetic polymers that may be developed that are biologically compatible.

[0103] The term “biologically compatible, synthetic polymers” includes, but is not limited to, homopolymers, copolymers, and blends, and any other combinations of the forgoing either together or with other polymers generally. The use of these polymers will depend on given applications and specifications required. A more detailed discussion of these polymers and types of polymers is set forth in Brannon-Peppas, Lisa, “Polymers in Controlled Drug Delivery,” Medical Plastics and Biomaterials, November 1997, the disclosure of which with regard to biologically compatible and / or synthetic polymers is incorporated herein by reference.

[0104] An AAV graft or at least a portion or end thereof may further comprise one or more additive(s). In various examples, one or more or all of the additive(s) is / are uniformly distributed (e.g., uniformly distributed in at least one fiber or the like) and / or encapsulated by an AAV graft or portion or end thereof (or the fibers / fiber material or the polymer(s) of a AAV graft or a portion or end thereof). In various examples, an additive is (or each of the additives is independently) uniformly distributed in an AAV graft or a portion or end thereof (e.g., in at least one fiber and / or encapsulated by or attached to the polymer(s) in at least one fiber or the like). Non-limiting examples of additives include one or more additive(s) chosen from therapeutic agents, drugs, dyes, indicator agents, conductive agents, and the like, and any combination thereof. In various examples, a conductive agent is chosen from salts, conductive polymers, and the like, and any combination thereof. In various examples, the additive(s) is / are a therapeutic agent, a dye, an indicator agent, a drug, and the like, and any combination thereof. In various examples, the additive is a therapeutic agent or a drug, configured to gradually deliver to a physiological environment after implanting an AAV graft into the physiological environment.

[0105] In various examples, an AAV graft or a portion or end thereof is configured to gradually deliver (e.g., gradually deliver or the like) one or more additive(s) (such as, therapeutic agent(s), drug(s), and any combination thereof) to a physiological environment (e.g., after introducing (such as, for example, implanting or the like) an AAV graft in the physiological environment (such as, for example, the physiological environment of an individual or the like)). In various examples, at least a portion or all of the additive(s) are thromboresistant agent(s) or the like. In various examples, at least a portion or all of the additive(s) is / are disposed on at least a portion of an exterior surface of a AAV graft wall.

[0106] In various examples, an AAV graft or a portion or end thereof comprises one or more non-porous and / or non-permeable layer(s) that (individually or in total) comprises about 0.1 to about 5% of the total thickness of the AAV graft. The individual non-porous and / or non- permeable inner layer(s) can be disposed anywhere within the AAV graft or a portion or end thereof from the lumen (the innermost surface (or wall) of the AAV graft or portion thereof, which may be defined by the innermost layer of the AAV graft or portion thereof) to the ablumen (the outermost surface (or wall) of the AAV graft or portion thereof, which may be defined by the outermost layer of the AAV graft or portion thereof). In various examples, a non- porous and / or non-permeable layer or layers is / are independently the lumen of the AAV graft orany portion thereof (e.g., the innermost layer of the AAV graft that forms the lumen of the AAV graft or portion thereof), disposed in the wall of the AAV graft or a portion or end thereof, the ablumen (e.g., the outermost layer of the AAV graft or portion thereof). Without intending to be bound by any particular theory, an AAV graft or portion thereof with a non-porous and / or non- permeable layer or layers, is considered leak-proof. In various examples, non-permeability is achieved by one or more independent mean(s) (such as, for example, hydrophobicity, small pore size, or the like, or any combination thereof). In various examples, a layer exhibits hydrophobicity and comprises small pore size or is nonporous.

[0107] In various examples, an AAV graft or a portion or end thereof is coated with a biocompatible and / or biodegradable material. In various examples, a layer (which may be a layer defining an inner volume of the AAV graft or portion thereof or an inner luminal surface of an AAV graft is coated with a biocompatible and / or biodegradable material. In various examples, the coating may be complete or partial. In various examples, the inner luminal surface of an AAV graft is coated completely with a thromboresistant agent, such as, for example, heparin and / or other compounds known to one of skill in the art to have similar anti-coagulant properties as heparin, to prevent, inhibit or reduce clotting within the inner lumen of an AAV graft.

[0108] In various examples, an AAV graft or a portion or end thereof comprises an electrospun biodegradable polyester core and an electrospun biodegradable polyester electrospun outer sheath surrounding the biodegradable polyester core with or without a thromboresistant agent coating the biodegradable AAV graft (which may be used to facilitate tissue regeneration in vivo by providing a structural frame for which tissue regeneration can occur).

[0109] In various examples, a first AAV graft portion 12 or end is (or comprises an end (or terminal) portion that is) compliant or the like with an artery in an individual. In various examples, a second AAV graft portion 14 or end is (or comprises an end (or terminal) portion that is) compliant or the like with a vein in or of an individual.

[0110] An AAV graft or a portion or end thereof may exhibit a desired compliance (such as, for example, axial compliance and / or radial compliance) and / or suture retention. In various examples, compliance is the ability of an AAV graft or a portion or end thereof, to change its dimension or diameter in the case of a tube, in response to the pressure it is subjected to (such as, for example, the blood pressure in an individual or the like). Without intending to be bound by any particular theory, it is considered an AAV graft may be a compliant AAV graft. In variousexamples, at least a portion, substantially all, or all of an AAV graft exhibits a radial compliance of about 1 to about 80% / 100 mmHg, including all 0.1 % / 100 mmHg values and ranges therebetween (e.g., 5 % / 100 mmHg, 10 % / 100 mmHg, 15% / 100 mmHg, 20% / 100 mmHg, 25% / 100 mmHg, 30% / 100 mmHg, 35% / l 00 mmHg, 40 % / 100 mmHg, 45% / l 00 mmHg, 50% / 100 mmHg, 55% / 100 mmHg, 60% / 100 mmHg, 65% / l 00 mmHg, 70% / 100 mmHg, 75% / 100 mmHg, or 80% / 100 mmHg). In various examples, a first portion (e.g., an arterial portion or the like) of an AAV graft or a portion or end thereof exhibits radial compliance (such as, for example, arterial radial compliance or the like) of about 3 to about 15% / 100mmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., about 5 to about 15% / lOOmmHg) and / or a second portion (e.g., a venous portion or the like) of an AAV graft exhibits radial compliance (such as, for example, venous compliance) of about 45 to about 60% / 100mmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., 50 to about 60% / 100mmHg). In various examples, an arteriovenous graft (e.g., at least a portion of an arteriovenous graft comprising a second end (which may be an arterial end)) exhibits arterial radial compliance (such as, for example, arterial radial compliance) of about 3 to about 15% / lOOmmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., about 5 to about 15% / lOOmmHg) and / or an arteriovenous graft (e.g., at least a portion of an arteriovenous graft comprising a first end (which may be a venous end)) exhibits venous radial compliance (such as, for example, venous compliance) of about 45 to about 60% / 100mmHg, including all 0.1% / lOOmmHg values and ranges therebetween (e.g., 50 to about 60% / 100mmHg). In various examples, a transition portion (such as, for example, a tapered transition portion, transition zone (e.g., a tapered transition zone or the like), a third AAV graft portion 16 or end, or the like) exhibits increasing compliance (or compliance defined by a gradient) from the end of (or a position proximate to an end of) the transition portion disposed on a first portion or end of AAV graft to the end of (or a position proximate to an end of) the transition portion disposed on a second portion or end of AAV graft. In various examples, a gradient is (or is defined by an increasing function (e.g., taper or the like). In various examples, an increasing function is a smooth function or the like. In various examples, the increasing function is a linear function (such as, for example, a decreasing smooth linear function or the like) or the like.

[0111] In various examples, an AAV graft or a portion or end thereof exhibits varying compliance along a longest linear axis (such, as, for example, a longitudinal axis or the like) ofthe AAV graft or the portion or end thereof. In various examples, compliance varies linearly or non-linearly and / or continuously or discontinuously along a longest linear axis (such, as, for example, a longitudinal axis or the like) of the AAV graft or the portion or end thereof. In various examples, compliance is greater at a second portion or end or proximate to a second portion or end of an AAV graft (such as, for example, a venous portion or end of an AAV graft or the like) relative to the compliance at or proximate to a first portion or end of the AAV graft (such as, for example, an arterial portion or end of the AAV graft or the like). In various examples, compliance is at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times greater or about 4 times to about 8 times, including all 0.1 times values and ranges therebetween, greater at a second portion or end or proximate to a second portion or end (which may be a venous portion or end) of an AAV graft relative to the compliance at or proximate to a first portion or end (which may be an arterial portion or end) of the AAV graft. In various examples, compliance is about 45 to about 60% / 100mmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., about 50 to about 60% / 100mmHg) at a second portion or end or proximate to a second portion or end of an AAV graft (such as, for example, a venous portion or end of an AAV graft or the like) and / or about 3 to about 15% / lOOmmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., about 5 to about % / 100mmHg) at a first portion or end or proximate to a first portion or end of an AAV graft (such as, for example, an arterial portion or end of the AAV graft or the like).

[0112] In various examples, an AAV graft (which may be a compliant AAV graft) comprises one or more layer(s) of fibers such as, for example, layer(s) independently comprising electrowritten fibers (which may be an outer layer, a sheath, or the like). In various examples, the electrowritten fibers of an individual layer comprise one or more polymer(s) (e.g., as described herein), a winding angle (e.g., as described herein), degree of fiber fusion (e.g., as described herein), or the like, or any combination thereof. In various examples, an AAV graft (which may be a compliant AAV graft) exhibits a compliance as described herein.

[0113] Without intending to be bound by any particular theory, it is considered that by selecting the material composition and / or one or more structural feature(s) of one or more or all the individual layers of an AAV graft or a portion or end thereof (e.g., in the case of electrowritten layers, changing fiber composition (e.g., as described herein), winding angle (e.g., as described herein), average frequency of fusion points (e.g., as described herein), one or moresystem configurations(s) (such as, for example, altering the electric potential(s) applied to the nozzle(s), if applied, altering spinneret translation, altering speed of collector rotation, or the like, or any combination thereof), or the like, or any combination thereof) the compliance of an AAV graft or a portion or end thereof can be tuned (e.g., to a compliance of about 1 to about 80% / 100 mmHg, including all 0.1 % / 100 mmHg values and ranges therebetween (e.g., about 5 % / 100 mmHg, about 10 % / 100 mmHg, about 15% / 100 mmHg, about 20% / 100 mmHg, about 25% / 100 mmHg, about 30% / 100 mmHg, about 35% / l 00 mmHg, about 40 % / l 00 mmHg, about 45% / 100 mmHg, about 50% / 100 mmHg, about 55% / l 00 mmHg, about 60% / 100 mmHg, about 65% / l 00 mmHg, about 70% / 100 mmHg, about 75% / l 00 mmHg, about 80% / l 00 mmHg, or about 1 to about 20% / 100 mmHg). In various examples, a method provides a compliant product as described herein.

[0114] An AAV graft can have various lengths. The length of an AAV graft is not particularly limited. In various examples, the length is selected for a particular use and / or individual. In various examples, an AAV graft comprises a length of about 5 cm to about 150 cm, including all 0.1 cm values and ranges therebetween (e.g., about 10 to about 100 cm or about 30 cm to about 50 cm). In various examples, an AAV graft comprises a length of at least about 12 inches.

[0115] In various examples, an AAV graft or a portion or end thereof is configured for use in dialysis or hemodialysis method. In various examples, an AAV graft is a shunt (such as, for example, an arteriovenous shunt) connecting a tubular structure of thicker wall (e g., artery) with a tubular structure of a thinner wall (e.g., vein) of an individual. In various examples, an AAV graft or a portion or end thereof is cannulatable. In various examples, an AAV graft or a portion or end thereof can withstand cannulation at its first AAV graft potion or first end (e.g., with a thicker wall and most of the transition zone except close to the thinner walled portion (portion 2, which will be the venous end of an arteriovenous shunt).

[0116] In various examples, an AAV graft or a portion or end thereof provides (or is configured to result in) a gradual pressure drop (which may be a substantially a linear pressure drop or a linear pressure drop) between the first AAV graft portion 12 or first end and the second AAV graft portion 14 or second end. In various examples, the shear pressure experienced by the AAV graft decreases gradually (which may be substantially a linear decrease or a linear decrease) as the inner diameter of the AAV graft increases.

[0117] In various examples, the first AAV graft portion 12 or end and the second AAV graft portion 14 or end do experience the same flow rates, but different shear stress and different pressure. In various examples, the pressure of an AAV graft or a portion or end thereof changes from about a typical systolic pressure (e.g., about 100 mmHg or higher) at a first AAV graft portion 12 or end to about 10 mmHg or lower at a second AAV graft portion 14 or end.

[0118] An AAV graft or a portion or end thereof can be made by various methods. Suitable methods are known in the art. In various examples, an AAV graft or a portion or end thereof is made by particulate leaching, salt fusion and leaching, electroaerosoling, electroprocessing (such as, for example, electrowriting (such as, for example, solution electrowriting, melt electrowriting, near-field solvent electrospinning, or the like), electrospinning, and the like, or any combination thereof), particulate leaching, extrusion, injection molding, 3-D printing, or the like, or any combination thereof. In various examples, an AAV graft or a portion or end thereof is a porous extruded graft. In various examples, a porous extruded graft comprises a porosity as described herein.

[0119] In various examples, a method of making a graft comprises a method disclosed in International Application No.: PCT / US2021 / 032740 (title “Functionalized Poly(Glycerol Sebacate)s and Uses Thereof’; filed May 17, 2021); International Application No.: PCT / US2021 / 056351 (title “Solution Electrowriting”; filed October 22, 2021); International Application No.: PCT / US2021 / 044230 (title “Chelation Crosslinked Polymers, Methods of Making Same, and Uses Thereof’; filed August 2, 2021); U.S. Pat. No. 10,582,996 (title “Biodegradable vascular grafts”; issued March 10, 2020); U.S. Pat. No. 9,938,373 (title “Methods of electrospinning and compositions made therefrom”; issued April 10, 2018); International Application No.: PCT / US2015 / 019146 (title “Electrospinning with sacrificial template for patterning fibrous constructs”; filed March 6, 2015), the disclosures of which relevant to grafts and / or methods of making grafts are incorporated herein by reference.

[0120] In an aspect, the present disclosure provides uses of asymmetric arteriovenous (AAV) grafts of the present disclosure. Non-limiting examples of uses of the AAV grafts are described herein.

[0121] An AAV graft can be used in a dialysis method, such as, for example, a hemodialysis method or the like, or the like. In various examples, a hemodialysis method comprises implanting an AAV graft in an individual and subsequently carrying out hemodialysis on theindividual. In various examples, a dialysis method comprises implantation of AAV graft (which is an arteriovenous shunt) or cannulation at the first AAV graft potion or first end of the AAV graft, or both. In various examples, there is reduction in observable narrowing and / or inflammation after the method is complete. Narrowing and / or inflammation can be observed by methods known in the art. In various examples, the presence and / or absence of narrowing and / or inflammation is observed by ultrasound, MRI, fluoroscopy, computerized tomography (CT) scan, or the like, or any combination thereof.

[0122] In various examples, an AAV graft is used as an arteriovenous shunt for dialysis access where “maturation” of about 2 to about 3 months is typical. In various examples, the implanting comprises fluidly connecting (e.g., by suturing or the like) a first orifice (e.g., venous orifice) to a vein of an individual and / or fluidly connecting (e.g., by suturing or the like) a second orifice (e.g., arterial orifice) to an artery of the individual. In various examples, the implanting comprises cannulation or the like.

[0123] At least a portion or all of an AAV graft may degrade after implantation in an individual. In various examples, at least 50%, such as, for example, about 55% to about 70%, about 80% to about 90%, about 90% to about 98%, including about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.5%, or about 99.99% of an AAV graft or a portion or end thereof degrades within about one year, such as, for example, within about 1 to about 10 months, including, but not limited to, within about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, or about 12 months of implantation.

[0124] In various examples, after implantation at least a portion or all of an AAV graft exhibits remodeling and / or an autologous structure. Remodeling is shown in FIG. 1. In various examples, within about 1 to about 10 months, including, but not limited to, within about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about7 months, about 8 months, about 9 months, about 10 months, about 11 months, or about 12 months of implantation least a portion or all of an AAV graft exhibits remodeling and / or an autologous structure.

[0125] An individual may be a human or non-human mammal or other animal. Non-limiting examples of non-human animals or mammals include cows, pigs, goats, mice, rats, rabbits, cats, dogs, or other agricultural mammals, pet, or service animals, and the like.

[0126] In an aspect, the present disclosure provides kits. Non-limiting examples of kits are provided herein.

[0127] In various examples, a kit comprises one or more asymmetric arteriovenous (AAV) graft(s) of the present disclosure. In various examples, a kit includes a closed or sealed package that comprises the AAV graft or AAV grafts. In various examples, the package comprises one or more closed or sealed vials, bottles, blister (bubble) packs, or any other suitable packaging for the sale, distribution, or use of the AAV graft(s). The printed material may include printed information. The printed information may be provided on a label, on a paper insert, printed on a packaging material, or the like. The printed information may include information that identifies the AAV grafts(s) and / or and instructions for use of AAV graft(s). The instructions may include information, such as, for example, information directed to a doctor and / or another health care provider. In various examples, the kit includes a label describing the contents of the kit and providing instructions regarding use of the contents of the kit to treat an individual.

[0128] The following Statements describe various examples of AAV grafts and uses thereof of the present disclosure and are not intended to be in any way limiting:Statement 1. A asymmetric arteriovenous (AAV) graft comprising a first end (e.g., an arterial end) comprising a first orifice, a second end (e.g., a venous end) comprising a second orifice, and a transition zone (e.g., a tapered transition end or the like) disposed between (e.g., in contact with or the like) the first end of the AAV graft and the second end of the AAV graft, where, for example, the transition zone begins at about a position at about 20 to about 80% (e.g., about 30 to about 80%) of the total length of the AAV graft from the terminus of the first end of the AAV graft, including all 0.1% values and ranges therebetween (e.g., about 40 to about 70%, or about 50 to about 60%) and / or the transition zone ends at about a position at about 90 to about 99% (e.g., about 95 to about 99%) of the total length of the AAV graft from the terminus of the first end of the AAV graft, including all 0.1% values and ranges therebetween (e.g., about 95%, about96%, about 97%, about 98%, or about 99%) OR An asymmetric (AAV) arteriovenous graft comprising a first AAV graft portion 12 (e.g., arterial anastomosis portion or arterial anastomosis portion end) comprising about 5 to about 80% (e.g., about 30 to about 80%) of the total length of the AAV graft and a first orifice, a second AAV graft portion 14 (e.g., a venous anastomosis portion or a venous anastomosis end) comprising about 1 to about 20% (e.g., about 1 to about 5 or about 1 to about 10%) of the total length of the AAV graft and a second orifice, a third AAV graft portion 16 (e.g., a transition portion, such as, for example, a tapered transition portion or the like or a transition zone, such as, for example, a tapered transition zone or the like) comprising about 15 to about 90% (e.g., about 15 to about 69%) of the total length of the AAV graft, where the third AAV graft portion 16 is disposed between the first AAV graft portion 12 and second AAV graft portion 14.Statement 2. An AAV graft according to Statement 1, where at least one cross-sectional dimension of a wall (e.g., wall thickness or the like) of the third AAV graft portion 16 disposed on (or proximate to or in contact with) the wall of the first AAV graft portion 12 is independently about ± 5% of (e.g., about the same as) a cross-sectional dimension of a wall (e.g., wall thickness or the like) of the first AAV graft portion 12 and / or at least one cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of the third AAV graft portion 16 is independently about ± 5% (e.g., ± 4%, ± 3%, ± 2%, ± 1%) of (e.g., about the same as) a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of the first AAV graft portion 12.Statement 3. An AAV graft according to Statement 1 or 2, where at least one cross-sectional dimension of a wall (e.g., wall thickness or the like) of the third AAV graft portion 16 disposed on (or proximate to or in contact with) the wall of the second AAV graft portion 14 is independently about ± 5% of (e.g., about the same as) a cross-sectional dimension of a wall (e.g., wall thickness or the like) of the first AAV graft portion 12 and / or at least one cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of the third AAV graft portion 16 is independently about ± 5% (e.g., ± 4%, ± 3%, ± 2%, ± 1%) of (e.g., about the same as) a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of the second AAV graft portion 14.Statement 4. An AAV graft according to any one of the preceding Statements, where the third AAV graft portion 16 comprises a first end portion disposed on (or proximate to or in contact with) the first AAV graft portion 12 and the first end portion comprises a first cross-sectional dimension (e.g., wall thickness or the like), and the third AAV graft portion 16 comprises a second end portion disposed on (or proximate to or in contact with) the second AAV graft portion 14 and the second end portion comprises a second cross-sectional dimension (e.g., wall thickness or the like), where the first cross-sectional dimension of the first end portion of the third AAV graft portion 16 is greater than the second cross-sectional dimension of the second end portion of the third AAV graft portion 16.Statement 5. An AAV graft according to any one of the preceding Statements, where the first AAV graft portion 12 or first end comprises a cross-sectional dimension (e.g., wall thickness) of about 0.4 mm to about 2 mm, including all 0.05 mm values and ranges therebetween (e.g., about 0.5 mm to about 1.8 mm, about 0.7 mm to about 1.2 mm).Statement 6. An AAV graft according to any one of the preceding Statements, where the first AAV graft portion 12 or first end comprises a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of about 3 mm to about 10 mm, including all 0.1 mm values and ranges therebetween (e.g., about 4 mm to about 8 mm, about 5 mm to about 7 mm).Statement 7. An AAV graft according to any one of the preceding Statements, where the second AAV graft portion 14 or second end comprises a cross-sectional dimension (e.g., wall thickness) of about 0.1 mm to about 1 mm, including all 0.05 mm values and ranges therebetween (e.g., about 0.2 mm to about 0.8 mm, about 0.2 mm to about 0.4 mm).Statement 8. An AAV graft according to any one of the preceding Statements, where the second AAV graft portion 14 or second end comprises a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft (such as, for example, an inner diameter or the like) of about 4 mm to about 12 mm, including all 0.1 mm values and ranges therebetween (e.g., about 5 mm to about 10 mm, about 6 mm to about 9 mm).Statement 9. An AAV graft according to any one of the preceding Statements, where at least a portion of a wall or all of the wall(s) comprise a plurality of pores, holes, cavities, or the like, or any combination thereof.Statement 10. An AAV graft according to Statement 9, where the porosity of the AAV graft is about 40 to about 99% (based on the total volume of the AAV graft wall), including all 0.1 porosity% values and ranges therebetween (e.g., about 50 to about 90% or about 50 to about 90%).Statement 11. An AAV graft according to Statement 9 or 10, where the pores of the AAV graft independently (or on average) comprise a cross-sectional dimension (e.g., a diameter or the like) of about 10 microns to about 200 microns, including all 0.1 micron values and ranges therebetween (e.g., about 20 microns to about 100 microns or about 25 to about 75 microns). Statement 12. An AAV graft according to any one of Statements 9-11, where the first AAV graft portion 12 comprises a first porosity and the second AAV graft portion 14 comprises a second porosity and the first porosity is greater than the second porosity.Statement 13. An AAV graft according to any one of the preceding Statements, where at least a portion of or all of the AAV graft (e.g., first AAV graft portion 12, second AAV graft portion 14, or third AAV graft portion 16, or the like, or any combination thereof) comprises one or more polymer(s) (such as, for example, one or more elastomer(s) or the like) or the like.Statement 14. An AAV graft according to any one of the preceding Statements, where at least a portion or all of the AAV graft (e.g., first AAV graft portion 12, second AAV graft portion 14, or third AAV graft portion 16, or the like, or any combination thereof) comprises a single layer structure or a multilayer structure, or the like.Statement 15. An AAV graft according to any one of the preceding Statements, where the AAV graft comprises at least one biocompatible polymer (such as, for example, a biocompatible elastomer or the like) or all the polymer(s) in the AAV graft are biocompatible polymer(s) (such as, for example, biocompatible elastomer(s) or the like).Statement 16. An AAV graft according to any one of the preceding Statements, where the AAV graft comprises at least one biodegradable polymer (such as, for example, a biodegradable elastomer or the like) or all the polymer(s) in the AAV graft are biodegradable polymer(s) (such as, for example, biodegradable elastomer(s) or the like).Statement 17. An AAV graft according to any one of the preceding Statements, where at least a portion or substantially all (e.g., all) of the AAV graft is biodegradable.Statement 18. An AAV graft according to any one of the preceding Statements, where the AAV graft comprises one or more additive(s).Statement 19. An AAV graft according to any one of the preceding Statements, where at least a portion or all of the AAV graft is made by electrospinning, electrowriting (such as, for example, solution electrowriting, melt electrowriting, near-field solvent electrospinning, or the like), particulate leaching, extrusion, injection molding, 3-D printing, or the like, or any combination thereof.Statement 20. A dialysis method comprising use of an AAV graft of any of the preceding Statements.Statement 21. An asymmetric (AAV) arteriovenous graft comprising a first AAV graft portion 12 comprising about 1 to about 66 percent (%) of a total length of the AAV graft, a second AAV graft portion 14 comprising about 1 to about 33% of a total length of the AAV graft, a third AAV graft portion 16 comprising about 1 to about 98% of the total length of the AAV graft, where the third AAV graft portion 16 is disposed between the first AAV graft portion 12 and second AAV graft portion 14, and where a wall thickness of the third AAV graft portion 16 decreases along at least a portion, substantially all, or all of a length of the third AAV graft portion 16 and / or an inner diameter of the third AAV graft portion 16 increases along at least a portion, substantially all, or all of a length of the third AAV graft portion 16.Statement 22. An AAV graft according to Statement 21, where the third AAV graft portion 16 comprises a decreasing gradient of a cross-sectional wall dimension (e.g., wall thickness or the like) and / or an increasing gradient of a cross-sectional dimension of an inner volume defined by a wall of the AAV graft (e g., inner diameter or the like) portion along at least a portion, substantially all, or all of a length of the third AAV graft portion 16 (or from the first AAV graft portion 12 to the second AAV graft portion 14).Statement 23. An AAV graft according to Statement 22, where the gradient is defined by a linear function or a step function.Statement 24. An AAV graft according to Statement 22 or 23, where the first AAV graft portion 12 exhibits a radial compliance of about 3 to about 15% / 100mmHg, including all % / 100mmHg values and ranges therebetween, and / or the second AAV graft portion 14 exhibits a radial compliance of about 45 to about 60% / 100mmHg, including all % / lOOmmHg values and ranges therebetween.Statement 25. An AAV graft according to any one of Statements 21-24, where at least one cross- sectional dimension of a wall of the third AAV graft portion 16 is independently about ± 5% of a(substantially the same or the same as) cross-sectional dimension of a wall of the first AAV graft portion 12 and / or at least one cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft of the third AAV graft portion 16 is independently about ± 5% of a (substantially the same or the same as) cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the first AAV graft portion 12.Statement 26. An AAV graft according to any one of Statements 21-25, where at least one cross- sectional dimension of a wall of the third AAV graft portion 16 is about ± 5% of a (substantially the same or the same as) cross-sectional dimension of a wall of the first AAV graft portion 12 and / or at least one cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft of the third AAV graft portion 16 is independently about ± 5% of a (substantially the same or the same as) cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft of the second AAV graft portion 14.Statement 27. An AAV graft according to any one of Statements 21-26, where the third AAV graft portion 16 comprises a first end portion disposed on the first AAV graft portion 12 and the first end portion comprises a first cross-sectional dimension, and the third AAV graft portion 16 comprises a second end portion disposed on the second AAV graft portion 14 and the second end portion comprises a second cross-sectional dimension, where the first cross-sectional dimension of the first end portion of the third AAV graft portion 16 is greater than the second cross-sectional dimension of the second end portion of the third AAV graft portion 16.Statement 28. An AAV graft according to any one of Statements 21-27, where the first AAV graft portion 12 comprises a cross-sectional dimension of about 0.4 mm to about 2 mm, including all 0.1 mm values and ranges therebetween.Statement 29. An AAV graft according to any one of Statements 21-28, where the first AAV graft portion 12 comprises a cross-sectional dimension of an inner volume defined by a wall of the first AAV graft portion of about 3 mm to about 10 mm, including all 0.1 mm values and ranges therebetween.Statement 30. An AAV graft according to any one of Statements 21-29, where the second AAV graft portion 14 comprises a cross-sectional dimension of about 0.1 mm to about 1 mm, including all 0.1 mm values and ranges therebetween.Statement 31 . An AAV graft according to any one of Statements 21-30, where the second AAV graft portion 14 comprises a cross-sectional dimension of an inner volume defined by a wall of the second AAV graft portion of about 4 mm to about 12 mm, including all 0.1 mm values and ranges therebetween.Statement 32. An AAV graft according to any one of Statements 21-31, where at least a portion of a wall or all of the wall(s) of the AAV graft comprise(s) a plurality of pores, holes, cavities, or any combination thereof.Statement 33. An AAV graft according to Statement 32, where the porosity of the AAV graft is about 40 to about 99% (based on the total volume of the AAV graft wall), including all 0.1% values and ranges therebetween.Statement 34. The AAV graft according to Statement 32 or 33, where the pores of the AAV graft independently comprise a cross-sectional dimension of about 10 microns to about 200 microns, including all 0.1 micron values and ranges therebetween.Statement 35. An AAV graft according to any one of Statements 32-34, where the first AAV graft portion 12 comprises a first porosity and the second AAV graft portion 14 comprises a second porosity and the first porosity is greater than the second porosity.Statement 36. An AAV graft according to any one of Statements 21-35, where at least a portion of or all of the AAV graft comprises one or more polymer(s).Statement 37. An AAV graft according to Statement 36, where one or more or all of the polymer(s) is / are elastomer(s).Statement 38. An AAV of Statement 36 or 37, where one or more or all of the polymer(s) is / are cross-linked polymer(s).Statement 39. An AAV graft according to any one of Statements 21-38, where at least a portion or substantially or all of the AAV graft comprises a single layer structure or a multilayer structure.Statement 40. An AAV graft according to any one of Statements 21-38, where the AAV graft comprises one or more polymer(s) and at least one or more or all the polymers is / are a biocompatible polymer or biocompatible polymers.Statement 41. An AAV graft according to any one of Statements 21-40, where at least a portion or substantially all or all of the AAV graft is biodegradable.Statement 42. An AAV graft according to any one of Statements 21-41, where the AAV graft comprises one or more additive(s).Statement 43. An AAV graft according to any one of Statements 21-42, where at least a portion or all of the AAV graft is made by electrospinning, electrowriting, particulate leaching, extrusion, injection molding, 3-D printing, or any combination thereof.Statement 44. A dialysis (such as, for example, hemodialysis or the like) method comprising implantation of the AAV graft of one of Statements 21-43.Statement 45. A dialysis method of Statement 44, the method further comprising, after implantation of the AAV graft, cannulation at the first AAV graft potion of the AAV graft. Statement 46. A dialysis method according to Statement 44 or 45, where the AAV graft is an arteriovenous shunt.

[0129] The steps of the methods described in the various examples disclosed herein are sufficient to carry out the methods of the present disclosure. Thus, in various examples, a method consists essentially of a combination of the steps of the methods disclosed herein. In various other examples, a method consists of such steps.

[0130] The following Examples are presented to illustrate the present disclosure. They are not intended to be limiting in any manner.EXAMPLE 1

[0131] This example provides examples of AAV grafts of the present disclosure, and methods of making and using same.

[0132] The goal was to demonstrate control of fiber orientation by solution electro-writing. A PCL graft was made with solution electro- writing, a semi-automated fabrication process. Electro-writing allows precision control of fiber diameter, spacing and winding angle (FIG. 3A). These 3 parameters are controlled in each layer through software on a computer-controlled graft fabrication device. For example, a dense fibrous layer can be placed anywhere in the graft to limit mass transfer. Polymer type can be switched when desired. The manufacturing process can be scaled up by using a multi-needle spinneret (FIG. 3).

[0133] The goal was to develop an example of an AV graft with portions having different geometries linked by a transition zone. Solution electrowriting was used to create a graft using PCL as an example polymer (FIG. 4B). By programing how fibers are deposited along a mandrelwith a gradual increase in diameter, one end of the graft has a smaller diameter and thicker wall (FIG. 4A, 1stcolumn from left, and FIG. 4C) where the other end has a larger diameter and thinner wall (FIG 4A, 4thcolumn from left, and FIG. 4C). The transition zone in the middle of the two ends allows a gradual change of diameter and wall thickness (FIG 4A, 2ndand 3rdcolumns from left, and FIG. 4C). The graft was cut into 4 segments to show the change in geometry.EXAMPLE 2

[0134] This example provides examples of AAV grafts of the present disclosure, and methods of making and using same.

[0135] FIGS. 10 and 11 are images of a tapered graft formed by extrusion featuring the 3 portion design, each portion having differing diameter and thickness. The material is bio-durable and the graft wall is non-porous. FIG. 10 shows one end (a first end) has an inner diameter of 3.4 mm and the opposite end (a second end) inner diameter is 5.0 mm.EXAMPLE 3

[0136] This example provides examples of AAV grafts of the present disclosure, and methods of making and using same.

[0137] The goal was to develop a vascular graft that transforms from a synthetic tube to an autologous vascular conduit with a graft where the geometry is a simple straight tube. Our expectation is that the host remodeling will be the same regardless of the geometry being a straight tube or a tube with varying diameter and thickness, as long as the graft is strong enough to handle the mechanical demand of the host circulation. The grafts were made of a biodegradable elastomeric poly (glycerol sebacate) (PGS) inner tube surrounded by a very think electrospun polycaprolactone (PCL) outer layer. The graft degraded over time. This transformation will benefit the whole body as it avoids chronic exposure of host cells to foreign materials. This transformation was demonstrated in animal models using an elastic and degradable synthetic graft. The host-remodeled the graft to be a nearly 100% autologous tissue with an endothelialized lumen and a vessel wall made of vascular extracellular matrix and mural cells. Consequently, we expect a higher patency rate because of the reduction of stenosis, matching compliance, and increased hemocompatibility. This technology combines the benefitsof fistula and graft while overcoming their limitations. Such a product will significantly reduce patients’ pain and healthcare cost associated with revisions and repeated procedures. Furthermore, the grafts were made of elastic fibers that bring two benefits: no kink upon bending and immediate cannulation. Needles push the elastic fibers apart, which recoil and seal the hole upon needle withdrawal.

[0138] After implantation, PGS begins to degrade into small molecules of glycerol and sebacate. Glycerol is a molecule that the body uses readily to build lipid membranes. Sebacate has been investigated as a carbon source to produce ATP for bed ridden patients. PCL has a long clinical history and is known to be safe and slow degrading. PCL was incorporated into the graft as a ‘safety net’ ensuring the graft will not rupture in cases of slower tissue regeneration rate. As the scaffold breaks down gradually, the patient’s own cells produce an autologous extracellular matrix and build up a new vascular conduit in its place.

[0139] The PGS-PCL graft degrades as host tissues replace and transform the graft into an autologous vascular conduit. This avoids long-term exposure to foreign materials. The autologous endothelium is expected to greatly improve hemocompatibility. The autologous nature of the remodeled graft will enable immune surveillance and greatly reduce infection.

[0140] The graft was made of highly elastic biodegradable polymers based on poly(glycerol sebacate) (PGS). The modulus of the polymer is in the range of human blood vessels, approximately lOOOx softer than PTFE. Fine control over the mechanical properties of the elastomer is shown by adjusting monomer ratio, polymerization parameters and substitution with palmitate. This allows the graft to closely match the biomechanical properties of the blood vessel. The elasticity of the graft promotes elastic fiber formation. In an adult patient, elastin synthesis is limited. However, it is believed that the capability of the graft to change dimensions under physiological blood pressure will still allow the host cells to produce undulating collagen fibers, as observed in animal studies. This is expected to enable their recruitment under mechanical loads (as seen in FIG. 7, as observed in a PGS-PCL graft transformed in a rat carotid interposition model), transforming the graft into a compliant vascular conduit than what would otherwise be a stiff conduit resulting from inflammation driven collagen deposition.

[0141] Host remodeling of PGS grafts into autologous conduits was demonstrated in a rat abdominal aorta model. The remodeled graft resembled the composition and mechanical properties of native aorta (FIG. 5A and B). Next a rat carotid artery model was used, a moredemanding environment for thrombosis. When compared head-to-head with autologous vein grafting, inflammation in the PGS-PCL composite graft resolved more rapidly and induced less smooth muscle cell proliferation than vein grafts (FIG. 6A-F and FIG. 7), indicating less likelihood of developing stenosis later.

[0142] Host remodeling was also tested in a sheep carotid model. PGS-PCL grafts were successfully implanted in sheep (FIG. 8A-C). Interposition implantation in sheep carotid artery demonstrated good handling and suturability. Duplex ultrasound examination at 2 weeks showed a patent graft. Histological examination showed host cell infiltration and endothelialization at anastomoses.

[0143] The designed AVG grafts are expected to transform into a patient’s own vascular conduit with matching compliance and endothelialized lumen. Causes of synthetic graft failure are the prolonged presence of foreign materials and compliance mismatch. The latter is true even for allograft and fistula because veins are far more compliant than arteries. Based on this, the new graft design with varying diameter and wall thickness (FIG. 2) will feature: 1. Fully biodegradable synthetic polymers with established biocompatibility. 2. An arterial-like segment that anastomoses with the patient’s artery; the compliance will be slightly higher than that of the native artery. 3. A transition zone with gradually increasing diameter accompanied by reduction in wall thickness, and 4. A venous zone matching the compliance of the vein that reduces the mechanical overload of the vein. The gradual increase in diameter should reduce blood pressure and is expected to reduce turbulence in the outflow vein. No previous product offers these features. It is expected that the portion of the graft with over 0.5 mm-thick wall can be cannulated. Allocating 1 cm of the arterial zone for suturing, the bulk of the graft will be a tough ‘canulation zone’.

[0144] To match the venous compliance, the venous zone will have a thin wall. On the other hand, a thicker wall of the arterial zone will reduce the compliance to approach that of the artery. The asymmetric design of the graft increases compliance matching of the shunt to its two distinct anastomoses from the very beginning (FIG. 2). It is expected that this design can increase the long-term patency of the graft.

[0145] Although the present disclosure has been described with respect to one or more particular example(s), it will be understood that other examples of the present disclosure may be made without departing from the scope of the present disclosure.

Claims

CLAIMS:

1. An asymmetric (AAV) arteriovenous graft comprising a first AAV graft portion comprising about 1 to about 66 percent (%) of a total length of the AAV graft, a second AAV graft portion comprising about 1 to about 33% of a total length of the AAV graft, a third AAV graft portion comprising about 1 to about 98% of the total length of the AAV graft, wherein the third AAV graft portion is disposed between the first AAV graft portion and second AAV graft portion, and wherein a wall thickness of the third AAV graft portion decreases along at least a portion, substantially all, or all of a length of the third AAV graft portion and / or an inner diameter of the third AAV graft portion increases along at least a portion, substantially all, or all of a length of the third AAV graft portion.

2. The AAV graft of claim 1, wherein the third AAV graft portion comprises a decreasing gradient of a cross-sectional wall dimension and / or an increasing gradient of a cross-sectional dimension of an inner volume defined by a wall of the AAV graft portion along at least a portion, substantially all, or all of a length of the third AAV graft portion.

3. The AAV graft of claim 2, wherein the gradient is defined by a linear function or a step function.

4. The AAV graft of claim 1, wherein the first AAV graft portion exhibits a radial compliance of about 3 to about 15% / lOOmmHg and / or the second AAV graft portion exhibits a radial compliance of about 45 to about 60% / 100mmHg.

5. The AAV graft of claim 1, wherein at least one cross-sectional dimension of a wall of the third AAV graft portion is independently about ± 5% of a cross-sectional dimension of a wall of the first AAV graft portion and / or at least one cross-sectional dimension of an inner volume ofthe AAV graft defined by the wall of the AAV graft of the third AAV graft portion is independently about ± 5% of a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the first AAV graft portion.

6. The AAV graft of claim 1, wherein at least one cross-sectional dimension of a wall of the third AAV graft portion is about ± 5% of a cross-sectional dimension of a wall of the first AAV graft portion and / or at least one cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft of the third AAV graft portion is independently about ± 5% of a cross-sectional dimension of an inner volume of the AAV graft defined by the wall of the AAV graft of the second AAV graft portion.

7. The AAV graft according to claim 1, wherein the third AAV graft portion comprises a first end portion disposed on the first AAV graft portion and the first end portion comprises a first cross-sectional dimension, and the third AAV graft portion comprises a second end portion disposed on the second AAV graft portion and the second end portion comprises a second cross-sectional dimension, wherein the first cross-sectional dimension of the first end portion of the third AAV graft portion is greater than the second cross-sectional dimension of the second end portion of the third AAV graft portion.

8. The AAV graft of claim 1, wherein the first AAV graft portion comprises a cross-sectional dimension of about 0.4 mm to about 2 mm.

9. The AAV graft of claim 1, wherein the first AAV graft portion comprises a cross-sectional dimension of an inner volume defined by a wall of the first AAV graft portion of about 3 mm to about 10 mm.

10. The AAV graft of claim 1, wherein the second AAV graft portion comprises a cross- sectional dimension of about 0.1 mm to about 1 mm.11 . The AAV graft of claim 1, wherein the second AAV graft portion comprises a cross- sectional dimension of an inner volume defined by a wall of the second AAV graft portion of about 4 mm to about 12 mm.

12. The AAV graft of claim 1, wherein at least a portion of a wall or all of the wall(s) of the AAV graft comprise(s) a plurality of pores, holes, cavities, or any combination thereof.

13. The AAV graft of claim 12, wherein the porosity of the AAV graft is about 40 to about 99% (based on the total volume of the AAV graft wall).

14. The AAV graft of claim 12, wherein the pores of the AAV graft independently comprise a cross-sectional dimension of about 10 microns to about 200 microns.

15. The AAV graft of claim 12, wherein the first AAV graft portion comprises a first porosity and the second AAV graft portion comprises a second porosity and the first porosity is greater than the second porosity.

16. The AAV graft of claim 1, wherein at least a portion of or all of the AAV graft comprises one or more polymer(s).

17. The AAV graft of claim 16, wherein one or more or all of the polymer(s) is / are elastomer(s).

18. The AAV graft of claim 16, wherein one or more or all of the polymer(s) is / are cross-linked polymer(s).

19. The AAV graft of claim 1, wherein at least a portion or all of the AAV graft comprises a single layer structure or a multilayer structure.

20. The AAV graft of claim 1, wherein the AAV graft comprises one or more polymer(s) and at least one or more or all the polymers is / are a biocompatible polymer or biocompatible polymers.21 . The AAV graft of claim 1, wherein at least a portion or substantially all or all of the AAV graft is biodegradable.

22. The AAV graft of claim 1, wherein the AAV graft comprises one or more additive(s).

23. The AAV graft of claim 1, wherein at least a portion or all of the AAV graft is made by electrospinning, electrowriting, particulate leaching, extrusion, injection molding, 3-D printing, or any combination thereof.

24. A hemodialysis method comprising implantation of the AAV graft of claim 1.

25. The hemodialysis method of claim 24, the method further comprising, after implantation of the AAV graft, cannulation at the first AAV graft potion of the AAV graft.

26. The hemodialysis method of claim 24, wherein the AAV graft is an arteriovenous shunt.

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