Advertisement

Acute Phase Pilot Evaluation of Small Diameter Long iBTA Induced Vascular Graft “Biotube” in a Goat Model

Open AccessPublished:January 10, 2022DOI:https://doi.org/10.1016/j.ejvsvf.2022.01.004

      Highlights

      • Small diameter, in body tissue architecture induced tissue engineered vascular graft.
      • Potential for patients with critical limb ischaemia without useable autologous vein.
      • Biocompatible and labour non-intensive tissue engineered vascular graft.

      Objective

      There is a need for small diameter vascular substitutes in the absence of available autologous material. A small diameter, long tissue engineered vascular graft was developed using a completely autologous approach called “in body tissue architecture technology (iBTA)”. The aim of this pilot study was to evaluate “Biotubes”, iBTA induced autologous collagenous tubes, for their potential use as small diameter vascular bypass conduits.

      Methods

      Biotubes (internal diameter 4 mm, length 50 cm, wall thickness 0.85 mm) were prepared by subcutaneous embedding of plastic moulds (Biotube Maker) in three goats for approximately two months. Allogenic Biotubes (length 10 cm [n = 2], 15 cm [n = 2], 22 cm [n = 2]) were bypassed to both carotid arteries by end to side anastomosis with their ligation between the anastomoses in another three goats. Residual Biotubes were examined for their mechanical properties. After four weeks, the harvested Biotubes were evaluated histologically.

      Results

      All Biotubes had sufficient pressure resistance, approximately 3000 mmHg. Although wall thickening occurred at two proximal anastomosis sites, all six grafts were patent without luminal thrombus formation, stenosis, or aneurysm deformation throughout the implantation period. Endothelial cells covered both anastomosis sites almost completely, with partial covering in the central portion of the grafts. Furthermore, α smooth muscle actin positive cells infiltrated the middle layer along almost the entire graft length.

      Conclusion

      This preliminary study showed that small diameter, long, tissue engineered Biotubes could function properly as arterial bypass conduits in a large animal for one month without any abnormal change in vascular shape. Thus, small diameter, long Biotubes are potentially viable conduits, which are biocompatible and labour non-intensive, and therefore, suitable for clinical practice. Additionally, Biotubes can start the regeneration process in a short period of time.

      Keywords

      Small diameter (4 mm), in body tissue architecture (iBTA) induced tissue engineered vascular grafts, “Biotubes” (length 10 cm [n = 2], 15 cm [n = 2], 22 cm [n = 2]), were used to bypass both carotid arteries of three goats. All six grafts showed no abnormal changes in vascular shape over the one month study period. Long, small diameter, tissue engineered Biotubes have the potential to be used as conduits in patients with chronic limb threatening ischaemia without available veins.

      Introduction

      The quality of the autologous vein conduit is a key consideration during infrapopliteal bypass surgery because alternative conduits, such as expanded polytetrafluoroethylene (ePTFE) or polyethylene (PET) grafts, and cadaver saphenous vein, are not as readily available.
      • Conte M.S.
      • Bradbury A.W.
      • Kolh P.
      • White J.V.
      • Dick F.
      • Fitridge R.
      • et al.
      Global vascular guidelines on the management of chronic limb-threatening ischemia.
      • Almasri J.
      • Adusumalli J.
      • Asi N.
      • Lakis S.
      • Alsawas M.
      • Prokop L.J.
      • et al.
      A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia.
      • Bradbury A.W.
      • Adam D.I.
      • Bell J.
      • Forbes J.F.
      • Fowkes F.G.R.
      • Gillespie I.
      • et al.
      Bypass versus angioplasty in severe ischemia of the leg (BASIL) trial: an intention-to treat analysis of amputation-free and overall survival in patients randomized to a bypass-first or a balloon angioplasty-first revascularization strategy.
      • Bradbury A.W.
      • Adam D.I.
      • Bell J.
      • Forbes J.F.
      • Fowkes F.G.R.
      • Gillespie I.
      • et al.
      Bypass versus angioplasty in severe ischemia of the leg (BASIL) trial: analysis of amputation free and overall survival by treatment received.
      However, autologous vein conduits are limited because of coexisting diseases, such as varicose veins and narrowed veins, or a lack of useable veins after use during previous coronary and peripheral bypass procedures. Consequently, there is a considerable need for alternative materials for autologous venous tissues that could be used for vascular reconstructive procedures in lower limb bypass.
      A clinically applicable long, small diameter, tissue engineered vascular graft (TEVG) was developed using a completely autologous approach called “in body tissue architecture technology (iBTA)”.
      • Nakayama Y.
      • Furukoshi M.
      • Terazawa T.
      • Iwai R.
      Development of long in vivo tissue-engineered “Biotube” vascular graft.
      The aim of this pilot study was to evaluate the potential use of “Biotubes”, iBTA induced autologous collagenous tubes, as vascular bypass conduits in a goat model.

      Materials and methods

      Experiments on all six goats were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (NIH Publication No. 85-23, 1996). All experiments were approved by the Tohoku University Ethics Committee (No. 2019AcA-041) and the Oita University Ethics Committee (No. 182201). The animals were raised in cages in the animal management room of Narita Animal Science (NAS) Laboratory Co., Ltd. (Chiba, Japan) at a temperature of 20–28 °C, humidity of 40–60%, and lighting time of 7 am–7 pm.

      Preparation of long Biotube

      In accordance with a previous report,
      • Nakayama Y.
      • Furukoshi M.
      • Terazawa T.
      • Iwai R.
      Development of long in vivo tissue-engineered “Biotube” vascular graft.
      long Biotubes were prepared using spiral plastic moulds (Biotube Maker, Biotube Co., Ltd., Tokyo, Japan) (Fig. 1). Four Biotube Makers per goat were embedded subcutaneously into three goats. About one month after the embedding procedure, the Makers were harvested. Biotubes (50 cm in length, 4 mm in diameter) were extracted by removing the Makers. All Biotubes were immersed in a 70% ethanol solution for 30 minutes and stored in a 10% ethanol solution. Thereafter, the Biotubes were washed with physiological saline for at least 10 minutes immediately before implantation or burst strength measurement.
      Figure thumbnail gr1
      Figure 1Preparation of Biotube by in body tissue architecture. (A) Biotube Maker as a plastic mould. (B, C) Subcutaneous embedding of a Biotube Maker in a goat. (D) Biotube Maker harvested with surrounding subcutaneous connective tissues. (E) Biotube formed around the spiral rod in the Biotube Maker. (F) Smooth luminal and protruded outer surfaces of Biotube. (G) Biotube (over 50 cm long) obtained by extraction from the spiral rod.

      Mechanical evaluations

      Storage Biotubes were cut to a width of 5 mm to obtain a total of 10 samples. Each sample was set on a uniaxial tensile tester (EZ-SX, Shimadzu, Kyoto, Japan) using two small pins (outer diameter 1.5 mm) and pulled at a speed of 10 mm/min until the sample broke.
      The breaking strength was defined as half of the maximum load (N) of the resulting load extension curve. The unit breaking force was defined as the breaking strength divided by the initial sample length. The estimated burst strength was calculated using the following formula:
      • Duprey A.
      • Khanafer K.
      • Schlicht M.
      • Avril S.
      • Williams D.
      • Berguer R.
      In vitro characterisation of physiological and maximum elastic modulus of ascending thoracic aortic aneurysms using uniaxial tensile testing.
      P=F/(L0Di)


      Di=dpin(π+2)+2Δsπ


      Δs=π(ddpin)+dpin2


      In these equations, P is the estimated internal burst pressure, F is the breaking strength, L0 is the initial longitudinal length of the ring sample, Di is the effective internal diameter, Δs is the distance between the pins, and dpin is the diameter of the pin.
      The sample thickness and width near the breaking position was measured using a 2D laser displacement sensor (LS-100CN, OPTEX FA, Kyoto, Japan). Young's modulus was calculated for the physiological pressure range according to a previously published method.
      • Duprey A.
      • Khanafer K.
      • Schlicht M.
      • Avril S.
      • Williams D.
      • Berguer R.
      In vitro characterisation of physiological and maximum elastic modulus of ascending thoracic aortic aneurysms using uniaxial tensile testing.

      Carotid artery bypass surgery

      Biotubes with an internal diameter of 4 mm (except one which was tapering to 3 mm at one end) and three different lengths (10 cm [n = 2], 15 cm [n = 2], and 22 cm [n = 2]) were implanted into both the left and the right carotid arteries of three goats (weights: 37.5, 41.0, and 44.9 kg) in an allogenic fashion (Fig. 2). Longitudinal incisions (10 cm for a 10 cm graft or 5 cm each in the proximal and distal neck for 15 and 22 cm grafts) were made, and the carotid arteries were exposed. Grafts of 15 and 22 cm were buried under subcutaneous tunnels. Thereafter, three minutes after intravenous administration of heparin sodium (200 IU/kg), the carotid artery was cross clamped. One end of the Biotube was anastomosed side to end to the proximal carotid artery with a continuous 7-0 polypropylene suture. The other end of the Biotube was similarly anastomosed to the carotid artery distally. The carotid artery was ligated between the proximal and the distal anastomotic sites. After implantation, the animals received antiplatelet drugs (clopidogrel 75 mg/head, PO, SID) for one month. One month after implantation, patency, form, and blood flow were observed using 2D, pulsed wave Doppler echography (Viamo PLT-1204ST, Canon Medical System, Tokyo, Japan). Subsequently, the Biotubes, including the carotid artery anastomoses, were harvested. Finally, the goats were euthanised.
      Figure thumbnail gr2
      Figure 2Bypass surgery. (A, B) Just after proximal anastomosis, neither bleeding nor leakage were seen. (C) Bypass surgery was completed with a 22 cm long Biotube. (D) One month post-operatively, no aneurysm formation was seen. (E) Colour Doppler ultrasound shows smooth blood flow. (F) 2D ultrasound shows neither stenosis nor thrombus formation. (G) Blood flow velocity was measured to be about 0.8–1.0 m/s using pulsed wave Doppler ultrasound.

      Histological examinations

      Biotubes were fixed in 4% paraformaldehyde saline solution (FUJIFILM Wako Pure Chemical Co., Osaka, Japan) and embedded in paraffin before 5 μm sections were obtained. For histochemical analysis, the sections were stained with haematoxylin and eosin (HE). For immunohistochemical analysis, sections were deparaffinised and incubated with anti-α-smooth muscle actin (α SMA) mouse monoclonal antibodies (1:200; ab7817, Abcam, Cambridge, UK) and CD31 rabbit polyclonal antibodies (1:100; ab28364, Abcam) overnight at 4°C. Thereafter, sections were incubated at room temperature for one hour with rabbit secondary antibodies to mouse IgG (Alexa Fluor 594) (1:1000; ab150128) and goat secondary antibodies to rabbit IgG (Alexa Fluor 488) (1:1000; ab150077), respectively. DAPI (ProLong Gold Antifade Mountant with DAPI, Thermo Fisher Scientific, Inc., MA, USA) was used as a nuclear counterstain. The sections were analysed using fluorescence microscopy (ECLIPSE-Ti, Nikon Corporation, Tokyo, Japan).

      Results

      Preparation of long tissue engineered Biotubes

      Long tissue engineered Biotubes were prepared using spiral plastic Biotube Makers that were embedded subcutaneously in goats for about one month. The adhesion between the Maker and surrounding tissue was mild and they could be pulled apart easily. After removing the connective tissues covering the Maker and subsequently removing its shell, Biotubes were found to form around the spiral mandrel (Fig. 1E). Twelve Biotubes were obtained from 12 moulds (four Makers per goat). However, two Biotubes had walls that were thinner on one side, while 10 Biotubes were formed over the entire length without defects and had a smooth luminal surface (Fig. 1F and G). The minimum estimated burst pressure was 1891 mmHg, the maximum was 4582 mmHg, and the average and standard deviation were 3355 ± 930 mmHg. Young's modulus of the Biotubes in the physiological pressure range was 3.70 ± 0.95 MPa, which was between that of goat carotid arteries (1.67 ± 0.52 MPa) and ePTFE grafts (5.69 ± 1.40 MPa).

      Carotid artery bypass surgery

      The Biotubes were very smooth, during the bypass procedure resembling a saphenous vein, and there was neither bleeding from the needle holes at the anastomosis site nor any haemorrhage from the Biotubes (Fig. 2A–C). All six grafts were palpated, and patency was retained during the one month study period. No dilation or rupture of the grafts was observed (Fig. 2D). Ultrasound showed that all grafts had a smooth blood flow pattern without mosaic flow (Fig. 2E), and there was no stenosis or thrombus formation in the graft (Fig. 2F). The blood flow velocity was maintained at about 0.8–1.0 m/s during the observation period (Fig. 2G). The estimated blood flow was approximately 460 mL/min.

      Histological examination

      At harvest, the Biotubes could be easily peeled off with little adhesion to the surrounding subcutaneous tissue and showed a native vascular like appearance (Fig. 3A). All Biotubes were patent without any abnormal changes in the vascular shape. Slight wall thickening occurred around the proximal anastomotic site of the 22 cm Biotubes (Fig. 3B), but the other anastomotic sites were white, very smooth, and continuously integrated with the end of the native carotid artery (Fig. 3B1, 2). At the proximal anastomotic site, there was little inflammation around the implanted Biotubes, and they were covered with native tissues (Fig. 3C). The walls of the Biotubes became thinner than 100 μm with increasing distance from the anastomotic site, indicating their degradation. Vascular tissues derived from the native artery extended gradually on the luminal surface of the Biotube wall. Native tissues also adhered to the outside of the Biotube wall, and the total thickness of the implant was 1 mm, not significantly different from that of the original Biotube.
      Figure thumbnail gr3
      Figure 3Macroscopic and microscopic histological evaluation. (A) Biotube was peeled off with little adhesion and showed native vascular like appearance. (B) Typical examples of the inside appearance of the anastomotic site: B1; one graft's proximal site, B2; distal site of the same graft, B3; another graft's proximal site. (C) Microscopic findings of one of the proximal anastomotic sites. The Biotube was left inside the red dotted line. C1, C2, C3; the Biotube became thinner than 100 μm as the distance from the anastomosis increased.
      To investigate the condition of the entire length of the implant region, tissues near the site of anastomosis (∗1 and ∗3 in Fig. 3A) and around the centre of the Biotube (∗2 in Fig. 3A) were observed (Fig. 4). Although all three implants had almost the same thickness (approximately 1 mm) and smooth, white luminal surfaces with no remarkable macroscopic change (Fig. 4A and B), fibrinoid derived blood components that thinly covered almost all luminal surfaces of the central part were observed on histological examination (Fig. 4C2). As shown in Fig. 3, the luminal surfaces of the Biotubes near both anastomotic regions were completely covered with an endothelial lining, similar to that of the anastomotic regions themselves (Fig. 4D1 and D3). On the other hand, there seemed to be no endothelial coverage in the central parts (Fig. 4D2). However, further magnification of the centre part of the Biotubes revealed round, CD31 positive, endothelial like cells lightly deposited on the surface of the fibrinoid layer (Fig. 5A1, B1 ). In addition, a CD31 positive endothelial layer was partially observed in the central part without a fibrinoid layer (Fig. 5A2, B2). The wall of the implant region occupied the α SMA positive smooth muscle cell layer (Fig. 4E1 – E3).
      Figure thumbnail gr4
      Figure 4Histological evaluation of cross section of the bilateral anastomotic sites (∗1 proximal, ∗3 distal parts in A Biotube) and at the central parts (∗2 in A Biotube). A1 – 3, B1 – 3: White and smooth luminal surfaces were observed in all three parts. C1, 3 and D1, 3: Luminal surface near both anastomotic sites was covered with endothelial lining. C2: A fibrinoid layer derived from blood components covered the luminal surface of the central parts. D2: There seemed to be no endothelial coverage on the centre parts. E1 – 3: α SMA positive smooth muscle cell layer occupied all parts of the Biotubes.
      Figure thumbnail gr5
      Figure 5Further magnified histological evaluation of the central part of the Biotube. A1 and B1: Round, CD31 positive endothelial like cells (arrows) were slightly deposited on the surface of the fibrinoid layer. A2 and B2: Partial CD31 positive endothelial layer was seen in the central part without a fibrinoid layer.

      Discussion

      This preliminary study has confirmed that “Biotubes”, iBTA induced small diameter long collagenous tubes, worked well as bypass graft conduits over the short term. Although vascular replacement with an autogenous vein offers the best mid and long term patency and limb salvage outcomes, particularly for patients with below knee arterial lesions and chronic limb threatening ischaemia, they are limited as mentioned above. Therefore, the development of innovative technologies targeting the fabrication of small calibre grafts instead of veins is essential. Such ideal grafts may be achieved by developing a TEVG; however, it is very challenging to achieve immune acceptance, the requisite tissue mechanics, low thrombogenicity, and immediate availability. Numerous approaches for the development of TEVGs have been described and reviewed extensively.
      • Pashneh-Tara S.
      • MacNeil S.
      • Claeyssens F.
      The tissue-engineered vascular graft-past, present, and future.
      Most techniques tend to involve scaffold based methods, using decellularised natural matrices, or tissue engineering by self assembly. These approaches need complex in vitro preparation steps, including cell culture, decellularised constructs, or the incorporation of synthetic materials.
      Previously, autologous prosthetic tissues were developed using the iBTA technique.
      • Nakayama Y.
      • Furukoshi M.
      • Terazawa T.
      • Iwai R.
      Development of long in vivo tissue-engineered “Biotube” vascular graft.
      ,
      • Nakayama Y.
      • Higashita R.
      • Shiraishi Y.
      • Umeno T.
      • Tajikawa T.
      • Yamada A.
      • et al.
      iBTA-induced Biotube blood vessels: 2020 update.
      iBTA is a cell free tissue engineering technology that can be used to produce autologous implantable tissues with the desired shape by simple subcutaneous embedding of a specially designed mould. The iBTA technique does not require complex steps or large scale plants, because the body itself works as a bioreactor.
      Fundamentally, TEVGs should satisfy the criteria for serving as a conduit to support blood flow; therefore, they must withstand the pressures exerted by the blood flow without bursting or permanently deforming through aneurysm formation. Biotubes in this in vitro study showed pressure resistance of approximately 3000 (1891–4582) mmHg comparable with the previously reported burst pressure (approximately 1700 mmHg) of the human saphenous vein.
      • Quint C.
      • Kondo Y.
      • Manson R.J.
      • Lawson J.H.
      • Dardik A.
      • Niklason L.E.
      Decellularized tissue-engineered blood vessel as an arterial conduit.
      Additionally, in this in vivo study, one month after being implanted as arterial bypass grafts, none of the Biotubes experienced bursting or bleeding events. Macroscopically and microscopically, no arterial deformation was observed in any graft over four weeks, which may be because the Young's modulus of Biotubes was close to that of carotid arteries.
      For over four decades, almost all in vitro TEVGs have been developed only to lengths of <10 cm; however, longer vascular grafts are needed for clinical use. This study examined the in vivo performance of long Biotubes (10–22 cm) in animal implantation experiments, using 50 cm Biotubes. The performance of the Biotubes during the operation was excellent, as evidenced by smooth handling and their short term durability without bleeding, dilatation, or thrombotic occlusion over one month. Histological examination of the Biotubes one month after implantation as arterial bypass grafts showed that their luminal surfaces were macroscopically very smooth, and there were no thrombi attached to the tissues at all. Previous histopathological evaluation of explanted vascular grafts demonstrated that the host cellular inflammatory response causes mechanical degradation because of inappropriate remodelling.
      • Keane T.J.
      • Badylak S.F.
      The host response to allogeneic and xenogeneic biological scaffold materials.
      • Randal-Vazquez M.E.
      • San Luis Veres A.
      • Pombo Otero J.
      • Segura Iglesias R.
      • Domenech Garcia N.
      • Andion Nunez C.
      Anatomopathological and immunohistochemical study of explanted cryopreserved arteries.
      • Kingston G.T.
      • Darby C.R.
      • Roerts I.S.
      The pathology of depopulated bovine ureter xenografts utilized for vascular access in haemodialysis patients.
      In addition, in the absence of autologous veins, biological grafts can also be used in infected fields, or in patients with a high risk of infection.
      • Chakfé N.
      • Diener H.
      • Lejay A.
      • Assadian O.
      • Berard X.
      • Caillon J.
      • et al.
      Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
      Recently, Lawson's group reported in their study of haemodialysis conduits in patients with end stage renal failure that most infiltrating host cells appeared to be non-immune and non-inflammatory in the fluorescence immunostaining of their explanted bioengineered vessels.
      • Gutowski P.
      • Gage S.M.
      • Guziewicz M.
      • Ilzecki M.
      • Kazimierczak A.
      • Kirkton R.D.
      • et al.
      Arterial reconstruction with human bioengineered acellular blood vessels in patients with peripheral arterial disease.
      ,
      • Kirkton R.D.
      • Santiago-Maysonet M.
      • Lowson J.H.
      • Tente W.E.
      • Dahl S.L.M.
      • Niklason L.E.
      • et al.
      Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation.
      Compared with the in vitro tissue engineered grafts reported by Lawson's group, Biotubes have about 1/3 of the production time, the same usage, less than 1/10 of the cost, and the same qualities. In addition, Biotubes are apparently labour non-intensive and have an advantage in terms of safety, as they are autologous tissues. When iBTA induced short vascular grafts were used as vascular access grafts in haemodialysis patients, completely autogenetic Biotubes were biocompatible, eliciting no immune or inflammatory response.
      • Nakayama Y.
      • Kaneko Y.
      • Okumura N.
      • Terazawa T.
      Initial 3-year results of first human use of an in-body tissue-engineered autologous “Biotube” vascular graft for hemodialysis.
      Even though Biotubes were heterogeneously implanted in this study, no inflammatory reactions were observed. In addition to the α SMA positive cells that infiltrated the middle layer of almost the entire length of the grafts, endothelial cell coverage was observed not only at both anastomotic sites, but also at the centre of the grafts. This was indicative of vascular wall reconstruction.

      Limitation and future studies

      In this study, the implanted period was short and the number of grafts was limited. Currently, longer term physicochemical and biological safety studies are also being conducted in parallel.
      • Nakayama Y.
      • Higashita R.
      • Shiraishi Y.
      • Umeno T.
      • Tajikawa T.
      • Yamada A.
      • et al.
      iBTA-induced Biotube blood vessels: 2020 update.
      Because autologous iBTA induced TEVG basically is an issue for emergency use, limited patients with chronic limb threatening ischaemia may be available; however, it could be desirable for patients without available autologous veins. Biotubes, used heterogeneously in this study, could be stored for several months. This means that patients at the pre-critical stage of peripheral artery disease may be candidates for revascularisation with Biotubes.

      Conclusion

      The results of this study indicate that long, small diameter, tissue engineered Biotubes are potentially viable conduits as they are biocompatible and labour non-intensive, and do not require in vitro cell processing, therefore, they can be used in clinical practice.

      Acknowledgements

      We would like to thank Yumiko Nakashima of Oita University and all the staff of NAS Laboratory for their kind management of the animals.

      Conflict of interest

      Yasuhide Nakayama, Ryuji Higashita, and Tomonori Oie are directors and stockholders of Biotube Co., Ltd. The other authors declare no conflicts of interest.

      Funding

      This research was supported by Biotube Co., Ltd. and grants from the Japan Agency for Medical Research and Development (AMED) .

      References

        • Conte M.S.
        • Bradbury A.W.
        • Kolh P.
        • White J.V.
        • Dick F.
        • Fitridge R.
        • et al.
        Global vascular guidelines on the management of chronic limb-threatening ischemia.
        Eur J Vasc Endovasc Surg. 2019; 58: S1-S109
        • Almasri J.
        • Adusumalli J.
        • Asi N.
        • Lakis S.
        • Alsawas M.
        • Prokop L.J.
        • et al.
        A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia.
        J Vasc Surg. 2018; 68: 624-633
        • Bradbury A.W.
        • Adam D.I.
        • Bell J.
        • Forbes J.F.
        • Fowkes F.G.R.
        • Gillespie I.
        • et al.
        Bypass versus angioplasty in severe ischemia of the leg (BASIL) trial: an intention-to treat analysis of amputation-free and overall survival in patients randomized to a bypass-first or a balloon angioplasty-first revascularization strategy.
        J Vasc Surg. 2010; 51: 5S-17S
        • Bradbury A.W.
        • Adam D.I.
        • Bell J.
        • Forbes J.F.
        • Fowkes F.G.R.
        • Gillespie I.
        • et al.
        Bypass versus angioplasty in severe ischemia of the leg (BASIL) trial: analysis of amputation free and overall survival by treatment received.
        J Vasc Surg. 2010; 51: 18S-31S
        • Nakayama Y.
        • Furukoshi M.
        • Terazawa T.
        • Iwai R.
        Development of long in vivo tissue-engineered “Biotube” vascular graft.
        Biomaterials. 2018; 185: 232-239
        • Duprey A.
        • Khanafer K.
        • Schlicht M.
        • Avril S.
        • Williams D.
        • Berguer R.
        In vitro characterisation of physiological and maximum elastic modulus of ascending thoracic aortic aneurysms using uniaxial tensile testing.
        Eur J Vasc Endovasc Surg. 2010; 39: 700-707
        • Pashneh-Tara S.
        • MacNeil S.
        • Claeyssens F.
        The tissue-engineered vascular graft-past, present, and future.
        Tissue Eng B Rev. 2016; 22: 68-100
        • Nakayama Y.
        • Higashita R.
        • Shiraishi Y.
        • Umeno T.
        • Tajikawa T.
        • Yamada A.
        • et al.
        iBTA-induced Biotube blood vessels: 2020 update.
        Kidney Dial. 2021; 1: 3-13
        • Quint C.
        • Kondo Y.
        • Manson R.J.
        • Lawson J.H.
        • Dardik A.
        • Niklason L.E.
        Decellularized tissue-engineered blood vessel as an arterial conduit.
        Proc Natl Acad Sci USA. 2011; 108: 9214-9219
        • Keane T.J.
        • Badylak S.F.
        The host response to allogeneic and xenogeneic biological scaffold materials.
        J Tissue Eng Regen. 2015; 9: 504-511
        • Randal-Vazquez M.E.
        • San Luis Veres A.
        • Pombo Otero J.
        • Segura Iglesias R.
        • Domenech Garcia N.
        • Andion Nunez C.
        Anatomopathological and immunohistochemical study of explanted cryopreserved arteries.
        Ann Vasc Surg. 2012; 26: 720-728
        • Kingston G.T.
        • Darby C.R.
        • Roerts I.S.
        The pathology of depopulated bovine ureter xenografts utilized for vascular access in haemodialysis patients.
        Histopathology. 2009; 55: 154-160
        • Chakfé N.
        • Diener H.
        • Lejay A.
        • Assadian O.
        • Berard X.
        • Caillon J.
        • et al.
        Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
        Eur J Vasc Endovasc Surg. 2020; 59: 339-384
        • Gutowski P.
        • Gage S.M.
        • Guziewicz M.
        • Ilzecki M.
        • Kazimierczak A.
        • Kirkton R.D.
        • et al.
        Arterial reconstruction with human bioengineered acellular blood vessels in patients with peripheral arterial disease.
        J Vasc Surg. 2020; 72: 1247-1258
        • Kirkton R.D.
        • Santiago-Maysonet M.
        • Lowson J.H.
        • Tente W.E.
        • Dahl S.L.M.
        • Niklason L.E.
        • et al.
        Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation.
        Sci Transl Med. 2019; 11eaau6934
        • Nakayama Y.
        • Kaneko Y.
        • Okumura N.
        • Terazawa T.
        Initial 3-year results of first human use of an in-body tissue-engineered autologous “Biotube” vascular graft for hemodialysis.
        J Vasc Access. 2020; 21: 110-115

      Comments

      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.