Native Vessels Research Articles

Fabrication and mechanical characterization of near field electrospun bioresorbable vascular grafts with fibrous architecture mimicking the arterial extracellular matrix

Cardiovascular disease, arteriosclerosis, is characterized by the thickening of blood vessel (arteries) walls restricting blood flow and is a global health problem. One treatment option is a surgical procedure utilizing an autologous or synthetic vascular graft to bypass or replace the diseased arterial segment. The goal of this study was to fabricate and mechanically characterize near field electrospun bioresorbable vascular grafts with a fibrous architecture that mimics the arterial extracellular matrix. Polydioxanone vascular constructs with circumferential fiber alignment angles of 15°/75° and 30°/60° (0° representing circumferential fiber alignment) were fabricated using a custom built near-field electrospinning (NFES) system. The vascular construct mechanical properties were compared to the saphenous vein (SV) and internal mammary artery (IMA) through longitudinal and circumferential uniaxial mechanical testing, suture retention, and burst pressure evaluations. The results demonstrated that the 15°/75° templates were closest to mimicking the native vessel target properties as compared to the 30°/60°; however, neither of the vascular template designs achieved or exceeded all the target values. For the ultimate tensile strength, both the constructs met the SV value on the circumferential axis (2.61 MPa) and the IMA value on the longitudinal axis (4.3 MPa). In terms of suture retention, the 15°/75° template was the only construct that was in the IMA and SV targeted range of 138–200 gf. Finally, the burst pressure testing results indicated that neither of the vascular constructs achieved the level of the SV or IMA (1600–3196 mmHg), however, the 15° constructs were within the lower error of the SV. In conclusion, with further design modifications, NFES constructs have demonstrated promise as small-diameter vascular grafts by mimicking native arterial architecture and mechanical properties.

Aneurysmatic Dilation of Autovenous Conduit After Coronary Bypass Graft: Clinical Case

Considering the prevalence of cardiovascular pathology and the increase in coronary interventions, including coronary artery bypass grafting (CABG), therapeutic observation and assessment of results, as well as possible complications in this cohort of patients is an urgent problem in the clinic of internal medicine. Autovenous conduits, namely the great saphenous vein, is one of the most common conduits during coronary artery bypass grafting. The reported incidence of minor dilation of great saphenous vein grafts used for CABG varies up to 14 %, but significant dilation of the aneurysm is rare. When performing coronary angiography or multispiral computed angiography, it is possible to establish the true size of the aneurysm, but the presence of mural thrombi can distort the true picture. Complications may include compression of the native coronary vessels, distal embolization, myocardial ischemia, compression of the right atrium, or fistula formation and rupture into the right atrium. The article discusses a rare clinical case of aneurysmal dilatation of an autovenous conduit up to 7.3 cm after 23 years of coronary artery bypass grafting. Considering that the development of aneurysms and pseudoaneurysms in the field of coronary bypass surgery can occur both early and late, clinical vigilance is necessary throughout the entire period of follow-up and informing the patient. The article discusses diagnostic and treatment algorithms for identifying aneurysms and pseudoaneurysms.

Mid-term Outcomes of Image-Guided Surgical Thromboembolectomy and Routine Intraoperative Angiography for Native Vessel Acute Lower-Limb-Threatening Ischemia.

Standard balloon-catheter thromboembolectomy (TE) is an established effective treatment for acute lower-limb ischemia (ALI) with recognized limitations when there is an underlying arterial lesion or thromboembolism of the infrapopliteal arteries. The aim of this study was to evaluate the efficacy and safety of image-guided surgical TE combined with routine intraoperative completion angiography in the treatment of ALI patients. Between September 2020 and August 2022, this prospective study included all consecutive adult patients presenting to a tertiary center with unilateral ALI of Rutherford class II due to thromboembolic occlusion of native arteries who underwent image-guided surgical TE and routine completion intraoperative angiography. Adjunctive endovascular techniques (hybrid revascularization) including plain balloon angioplasty (PTA)±stenting or on-table lysis were used if underlying arterial lesions or residual thrombosis were detected on the intraoperative angiography, respectively. The primary outcome measures included technical success and 30-day major amputation rate. Perioperative complications, 1-year primary and secondary patency, limb salvage, mortality, and amputation-free survival rates were endorsed as secondary outcome measures. Image-guided surgical thrombectomy was done for 109 ALI patients (109 limbs), provisionally diagnosed as embolic (57 patients, 52.3%) or thrombotic (52 patients, 47.7%) arterial occlusion. Thromboembolectomy without adjunctive endovascular treatment was done in 38 patients (34.86%), whereas 71 patients (65.14%) required adjunctive PTA±stenting of underlying arterial lesions (60, 55.05%) or on-table lysis±PTA of residual thrombosis (11, 10.09%). The overall technical success rate was 92.66%. At 30 days, amputation and mortality rates were 3.67% and 5.5%, respectively. None of the patients had thrombectomy-induced arterial injuries. One-year follow-up data were available for 81 patients (74.3%). The Kaplan-Meier estimate of the 12-month primary and secondary patency, limb salvage, and amputation-free survival rates was 76.5%±0.04, 91.5%±0.03, 90.6±0.03, and 91.4±0.03%, respectively. Image-guided TE combined with routine intraoperative angiography is a safe and effective technique for surgical TE in acute lower-limb ischemia patients with the advantage of immediate identification and treatment of underlying arterial lesions or residual thrombosis for optimal revascularization. The present study has confirmed the safety and effectiveness of image-guided thromboembolectomy combined with routine use of intraoperative angiography during surgical treatment of acute lower limb ischemia in terms of immediate identification and treatment of underlying arterial lesions or residual thrombosis for optimal revascularization. This technique also facilitates selective passage of Fogarty balloon catheter into infrapopliteal arteries from the femoral approach which is traditionally done by exploration of the popliteal trifurcation or tibial arteries under regional or general anesthesia. Using this technique can guide the operating surgeon for adequate balloon manipulation and inflation to avoid iatrogenic vessel injury.

Tuning Recombinant Perlecan Domain V to Regulate Angiogenic Growth Factors and Enhance Endothelialization of Electrospun Silk Vascular Grafts.

Synthetic vascular grafts are used to bypass significant arterial blockage when native blood vessels are unsuitable, yet their propensity to fail due to poor blood compatibility and progressive graft stenosis remains an intractable challenge. Perlecan is the major heparan sulfate (HS) proteoglycan in the blood vessel wall with an inherent ability to regulate vascular cell activities associated with these major graft failure modes. Here the ability of the engineered form of perlecan domain V (rDV) to bind angiogenic growth factors is tuned and endothelial cell proliferation via the composition of its glycosaminoglycan (GAG) chain is supported. It is shown that the HS on rDV supports angiogenic growth factor signaling, including fibroblast growth factor (FGF) 2 and vascular endothelial growth factor (VEGF)165, while both HS and chondroitin sulfate on rDV are involved in VEGF189 signaling. It is also shown that physisorption of rDV on emerging electrospun silk fibroin vascular grafts promotes endothelialization and patency in a murine arterial interposition model, compared to the silk grafts alone. Together, this study demonstrates the potential of rDV as a tunable, angiogenic biomaterial coating that both potentiates growth factors and regulates endothelial cells.

Design and fabrication of dual-layer PCL nanofibrous scaffolds with inductive influence on vascular cell responses

Confronted with the profound threat of cardiovascular diseases to health, vascular tissue engineering presents potential beyond the limitations of autologous and allogeneic grafts, offering a promising solution. This study undertakes an initial exploration into the impact of a natural active protein, elastin, on vascular cell behavior, by incorporating with polycaprolactone to prepare fibrous tissue engineering scaffold. The results reveal that elastin serves to foster endothelial cell adhesion and proliferation, suppress smooth muscle cell proliferation, and induce macrophage polarization. Furthermore, the incorporation of elastin contributes to heightened scaffold strength, compliance, and elongation, concomitantly lowering the elastic modulus. Subsequently, a bilayer oriented polycaprolactone (PCL) scaffold infused with elastin is proposed. This design draws inspiration from the cellular arrangement of native blood vessels, leveraging oriented fibers to guide cell orientation. The resulting fiber scaffold exhibits commendable mechanical properties and cell infiltration capacity, imparting valuable insights for the rapid endothelialization of vascular scaffolds.

Small diameter vascular grafts: progress on electrospinning matrix/stem cell blending approach.

The exploration of the next-generation small diameter vascular grafts (SDVGs) will never stop until they possess high biocompatibility and patency comparable to autologous native blood vessels. Integrating biocompatible electrospinning (ES) matrices with highly bioactive stem cells (SCs) provides a rational and promising solution. ES is a simple, fast, flexible and universal technology to prepare extracellular matrix-like fibrous scaffolds in large scale, while SCs are valuable, multifunctional and favorable seed cells with special characteristics for the emerging field of cell therapy and regenerative medicine. Both ES matrices and SCs are advanced resources with medical application prospects, and the combination may share their advantages to drive the overcoming of the long-lasting hurdles in SDVG field. In this review, the advances on SDVGs based on ES matrices and SCs (including pluripotent SCs, multipotent SCs, and unipotent SCs) are sorted out, and current challenges and future prospects are discussed.

A Comparison of Three-Layer and Single-Layer Small Vascular Grafts Manufactured via the Roto-Evaporation Method.

This study used the roto-evaporation technique to engineer a 6 mm three-layer polyurethane vascular graft (TVG) that mimics the architecture of human coronary artery native vessels. Two segmented polyurethanes were synthesized using lysine (SPUUK) and ascorbic acid (SPUAA), and the resulting materials were used to create the intima and adventitia layers, respectively. In contrast, the media layer of the TVG was composed of a commercially available polyurethane, Pearlbond 703 EXP. For comparison purposes, single-layer vascular grafts (SVGs) from individual polyurethanes and a polyurethane blend (MVG) were made and tested similarly and evaluated according to the ISO 7198 standard. The TVG exhibited the highest circumferential tensile strength and longitudinal forces compared to single-layer vascular grafts of lower thicknesses made from the same polyurethanes. The TVG also showed higher suture and burst strength values than native vessels. The TVG withstood up to 2087 ± 139 mmHg and exhibited a compliance of 0.15 ± 0.1%/100 mmHg, while SPUUK SVGs showed a compliance of 5.21 ± 1.29%/100 mmHg, akin to coronary arteries but superior to the saphenous vein. An indirect cytocompatibility test using the MDA-MB-231 cell line showed 90 to 100% viability for all polyurethanes, surpassing the minimum 70% threshold needed for biomaterials deemed cytocompatibility. Despite the non-cytotoxic nature of the polyurethane extracts when grown directly on the surface, they displayed poor fibroblast adhesion, except for SPUUK. All vascular grafts showed hemolysis values under the permissible limit of 5% and longer coagulation times.

The Edifice of Vasculature-On-Chips: A Focused Review on the Key Elements and Assembly of Angiogenesis Models.

The conception of vascularized organ-on-a-chip models provides researchers with the ability to supply controlled biological and physical cues that simulate the in vivo dynamic microphysiological environment of native blood vessels. The intention of this niche research area is to improve our understanding of the role of the vasculature in health or disease progression in vitro by allowing researchers to monitor angiogenic responses and cell-cell or cell-matrix interactions in real time. This review offers a comprehensive overview of the essential elements, including cells, biomaterials, microenvironmental factors, microfluidic chip design, and standard validation procedures that currently govern angiogenesis-on-a-chip assemblies. In addition, we emphasize the importance of incorporating a microvasculature component into organ-on-chip devices in critical biomedical research areas, such as tissue engineering, drug discovery, and disease modeling. Ultimately, advances in this area of research could provide innovative solutions and a personalized approach to ongoing medical challenges.

High-precision 3D printing of multi-branch vascular scaffold with plasticized PLCL thermoplastic elastomer

Three-dimensional (3D) printing has emerged as a transformative technology for tissue engineering, enabling the production of structures that closely emulate the intricate architecture and mechanical properties of native biological tissues. However, the fabrication of complex microstructures with high accuracy using biocompatible, degradable thermoplastic elastomers poses significant technical obstacles. This is primarily due to the inherent soft-matter nature of such materials, which complicates real-time control of micro-squeezing, resulting in low fidelity or even failure. In this study, we employ Poly (L-lactide-co-ϵ-caprolactone) (PLCL) as a model material and introduce a novel framework for high-precision 3D printing based on the material plasticization process. This approach significantly enhances the dynamic responsiveness of the start-stop transition during printing, thereby reducing harmful errors by up to 93%. Leveraging this enhanced material, we have efficiently fabricated arrays of multi-branched vascular scaffolds that exhibit exceptional morphological fidelity and possess elastic moduli that faithfully approximate the physiological modulus spectrum of native blood vessels, ranging from 2.5 to 45 MPa. The methodology we propose for the compatibilization and modification of elastomeric materials addresses the challenge of real-time precision control, representing a significant advancement in the domain of melt polymer 3D printing. This innovation holds considerable promise for the creation of detailed multi-branch vascular scaffolds and other sophisticated organotypic structures critical to advancing tissue engineering and regenerative medicine.

Quantifying Inferior Vena Cava Compliance and Distensibility in an In Vivo Ovine Model Using 3D Angiography.

Synthetic vascular grafts overcome some challenges of allografts, autografts, and xenografts but are often more rigid and less compliant than the native vessel into which they are implanted. Compliance matching with the native vessel is emerging as a key property for graft success. The current gold standard for assessing vessel compliance involves the vessel's excision and ex vivo biaxial mechanical testing. We developed an in vivo method to assess venous compliance and distensibility that better reflects natural physiology and takes into consideration the impact of a pressure change caused by flowing blood and by any morphologic changes present. This method is designed as a survival procedure, facilitating longitudinal studies while potentially reducing the need for animal use. Our method involves injecting a 20 mL/kg saline bolus into the venous vasculature, followed by the acquisition of pre and post bolus 3D angiograms to observe alterations induced by the bolus, concurrently with intravascular pressure measurements in target regions. We are then able to measure the circumference and the cross-sectional area of the vessel pre and post bolus. With these data and the intravascular pressure, we are able to calculate the compliance and distensibility with specific equations. This method was used to compare the inferior vena cava's compliance and distensibility in native unoperated sheep to the conduit of sheep implanted with a long-term expanded polytetrafluorethylene (PTFE) graft. The native vessel was found to be more compliant and distensible than the PTFE graft at all measured locations. We conclude that this method safely provides in vivo measurements of vein compliance and distensibility.

Biomimetic approach to the design of artificial small‑diameter blood vessels

Objective: To create 2-mm diameter multilayer porous tubular scaffolds (PTS) with characteristics that resemble small-diameter native blood vessels in terms of characteristics.Materials and methods. PTS made of polycaprolactone (PCL, MM 80000) with a PCL-made sealing coat/layer with gelatin addition (PCL-gelatin) with a diameter of 2 mm were created by electrospinning (NANON-01A). Bioactive coating was applied to the PTS surface by sequential incubation in solutions of bovine serum albumin, heparin (Hp), and platelet lysate (PL). Cytotoxicity was investigated under conditions of direct contact of PTS with a monolayer of NIH/3T3 mouse fibroblasts. Viability of human umbilical vein endothelial cells (EA.hy926) was evaluated using Live/Dead® Viability/Cytotoxicity Kit. Permeability and blood flow parameters of the PTS implanted in the infrarenal section of the rat aorta were recorded using Doppler imaging.Results. A three-layer PTS construct with an inner diameter of 2 mm was developed. Its inner and outer layers were formed from 0.2 mL of PCL solution, and the middle sealing coat/layer was from 0.5 mL of PCL with addition of 30% (by weight of polymer) gelatin. Introduction of the sealing coat/layer reduced surgical porosity (SP) from 56.2 ± 8.7 mL/(cm2·min) for a single-layer PTS made of pure PCL to 8.9 ± 2.6 mL/(cm2·min) for a three-layer PTS. The resulting PTS demonstrated physicomechanical characteristics similar to those of native blood vessels; it also showed no cytotoxicity. Application of a bioactive coating of Hp and PL allowed for increased in vitro adhesion and proliferation of endothelial cells. The technique of implantation of 10 mm long fragments of three-layer PTS into the infrarenal section of a rat aorta was corrected, thus minimizing blood loss and narrowing the anastomosis site. In an acute experiment, it was proven that the prostheses were patent and that blood flow parameters (systolic and diastolic velocity, resistivity index) were close to the corresponding indicators of native rat aorta.Conclusion. The developed three-layer PTS constructs have low SP and physicomechanical properties close to those of native blood vessels. Bioactive coating improves the in vitro matrix properties of PTS relative to human endothelial cells. At short-term implantation into the aorta of experimental animals, PTS showed no early thrombosis, while blood flow parameters were close to those of native rat aorta. Thus, three-layer PTS with bioactive coating can be used as a scaffold for creation of in situ tissue-engineered construct of a small-diameter blood vessel.

Measurement System for Compliance in Tubular Structures

Tubular structures such as blood vessels, intestines, and the trachea are common in various life forms. This paper describes a measurement system to test the mechanical compliance of tubular structures. The novelty of the system lies in its hardware and software. Here we use vascular graft as an example to demonstrate the utility of the system. A fully synthetic vascular graft would ideally mimic the mechanical and architectural properties of a native blood vessel. Therefore, mechanical testing of the graft material under physiological pressure is crucial to characterizing its potential in vivo performance. The device operates through a low-cost Arduino-based control system that simulates and measures cyclic fluid pressure changes over time and a laser micrometer that measures diameter changes with pressure. This system is low-cost, assuming one already has access to a laser micrometer. In contrast to previous methods, this system offers a simple, low-cost, and customizable option to measure compliance and is equipped with data acquisition/analysis programs. These programs include a MATLAB application that processes and synchronizes Arduino Uno pressure signals and LabChart Pro diameter readings. Lastly, this paper explains the hardware and software of the measurement system. The system is beneficial for testing the pressure-diameter relationship of tubular structures of varying sizes and materials. KEYWORDS: Tubular Structures; Compliance; Data Acquisition System; Physiological Pressure; Diameter Change; Arduino Uno; LabChart Pro; MATLAB

Native coronary artery or bypass graft percutaneous coronary intervention in patients after previous coronary artery bypass surgery: A large nationwide analysis from the Netherlands Heart Registration

BackgroundPatients with previous coronary artery bypass surgery (CABG) who require repeat revascularization frequently undergo percutaneous coronary intervention (PCI). We sought to identify factors associated with the decision to intervene on the native vessel versus a bypass graft and investigate their outcomes in a large nationwide prospective registry. MethodsWe identified patients who underwent PCI with a history of prior CABG from the Netherlands Heart Registration between 2017 and 2021 and stratified them by isolated native vessel PCI versus PCI including at least one venous- or arterial graft. The primary endpoint of major adverse cardiac events (MACE) was a composite of all-cause death and target vessel revascularization (TVR) at one-year post PCI. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), and TVR at 30 days. ResultsOut of 154,146 patients who underwent PCI, 12,822 (8.3%) had a prior CABG. Isolated native vessel PCI was most frequently performed (75.2%), while an acute coronary syndrome (ACS) presentation was most strongly associated with graft interventions. The primary outcome of MACE at one-year post PCI occurred more frequently in interventions including grafts compared with native vessels alone (19.7% vs. 14.3%; adjOR 1.267; 95% CI 1.101–1.457); p < 0.001) driven by TVR. There was however no difference in mortality or the key secondary endpoint between the two groups. ConclusionIn this nationwide prospective registry, ACS presentation was strongly associated with bypass graft PCI. At one year after PCI, interventions including bypass grafts had a higher composite of MACE compared with isolated native vessel interventions.

Engineering pre-vascularized 3D tissue and rapid vascular integration with host blood vessels via co-cultured spheroids-laden hydrogel

Recent advances in regenerative medicine and tissue engineering have enabled the biofabrication of three-dimensional (3D) tissue analogues with the potential for use in transplants and disease modeling. However, the practical use of these biomimetic tissues has been hindered by the challenge posed by reconstructing anatomical-scale micro-vasculature tissues. In this study, we suggest that co-cultured spheroids within hydrogels hold promise for regenerating highly vascularized and innervated tissues, both in vitro and in vivo. Human adipose-derived stem cells (hADSCs) and human umbilical vein cells (HUVECs) were prepared as spheroids, which were encapsulated in gelatin methacryloyl hydrogels to fabricate a 3D pre-vascularized tissue. The vasculogenic responses, extracellular matrix production, and remodeling depending on parameters like co-culture ratio, hydrogel strength, and pre-vascularization time for in vivo integration with native vessels were then delicately characterized. The co-cultured spheroids with 3:1 ratio (hADSCs/HUVECs) within the hydrogel and with a pliable storage modulus showed the greatest vasculogenic potential, and ultimately formed in vitro arteriole-scale vasculature with a longitudinal lumen structure and a complex vascular network after long-term culturing. Importantly, the pre-vascularized tissue also showed anastomotic vascular integration with host blood vessels after transplantation, and successful vascularization that was positive for both CD31 and alpha-smooth muscle actin covering 18.6 ± 3.6 μm2 of the luminal area. The described co-cultured spheroids-laden hydrogel can therefore serve as effective platform for engineering 3D vascularized complex tissues.

Morphologic features of prostate cancer-encased native vessels: An image analysis study

BackgroundVasculature plays a crucial role in the progression of prostate cancer (PC). Changes to the prostatic native vessels have not been studied since 2000 when Garcia et al. demonstrated marked media hypercellularity and increased artery thickness in prostatic native arteries within PC. We aim to further evaluate and characterize prostatic native vessels with a more accurate method with the use of virtual slides and digital analysis. DesignPathologist-annotated whole-mount digital slides from 96 entirely submitted prostatectomies were annotated for PC (color-coded by Gleason) using Omero platform. A subset of 44 cases met criteria for further analysis of media thickness, cellularity, and wall thickness to lumen ratio. Cases were included based on containing ≥5 native arteries (≥100 µm diameter) encased on at least 3 sides by PC, with vessels (≥100 µm diameter) designated as controls if they were ≥ 1000 µm away from PC. Annotated vessels were segmented and processed using Matlab 2023b. Mean media thickness (corrected for oblique sections), media: lumen ratio (based on numbers of pixels), and media cellularity (nuclei count) were studied by analysis with SPSS by linear mixed model with nested random effects for subject and slide to account for repeated measures. ResultsVessels encased by PC showed greater media thickness (p=0.02), cellularity (p=0.02) and wall thickness/lumen ratio (p= <0.001) compared to vessels away from PC. These values showed an increasing trend according to stage in cellularity (p=0.14), media thickness (p=0.12) and wall thickness/ lumen ratio (p= 0.33) with higher stage (pT3). A Gleason group comparison showed a borderline-significant gradewise trend when analyzing wall thickness/lumen ratio (p=0.06). Grade 5 emerged as significantly different (p=0.02) from grades 3 or 4 non-cribriform. ConclusionsSimilar to the 2000 study, increased media thickness and hypercellularity of vessels encased by PC were evident compared to controls. Borderline grade-dependent increased vessel cellularity changes were seen, suggesting a possible role in PC progression; the predictive value of these changes for outcome is uncertain. Whether the etiology of changes reflects locally increased intravascular pressure of vessels within tumor should be investigated.

Use of Flow-through Free Flaps in Head and Neck Reconstruction.

Reconstructive obstacles in composite head and neck defects are compounded in reoperated, traumatized, irradiated, and vessel-depleted surgical fields. In cases that require multiple free flaps, recipient vessel accessibility and inset logistics become challenging. Strategic flow-through flap configurations mitigate these issues by supplying arterial inflow and venous outflow to a second flap in a contiguous fashion. This approach (1) permits the use of a singular native recipient vessel, (2) increases the reach of the vascular pedicle, avoiding the need for arteriovenous grafting, and (3) allows for a greater three-dimensional flexibility in configuring soft tissue and bony flap inset. To demonstrate this technique, we conducted a retrospective review of all head and neck reconstruction patients presenting to us from March 2019 to April 2021. We present seven oncological and two traumatic patients (N = 9) who received flow-through free flaps for head and neck reconstruction. The most common flap used as the flow-through flap was the anterolateral thigh flap (N = 7), followed by the fibula flap (N = 2). Mean follow-up time was 507 days. No flap failures occurred. In head and neck reconstruction, the use of the flow-through principle enables uninterrupted vascular flow for two distinct free flaps in single-stage reconstruction for patients with vessel-depleted, irradiated, and/or reoperated fields. We demonstrate that flow-through flaps in the head and neck may be used successfully for a variety of cases and flaps.

Carotid Artery Bypass Surgery of In-Body Tissue Architecture-Induced Small-Diameter Biotube in a Goat Model: A Pilot Study.

Biotubes are autologous tubular tissues developed within a patient's body through in-body tissue architecture, and they demonstrate high potential for early clinical application as a vascular replacement. In this pilot study, we used large animals to perform implantation experiments in preparation for preclinical testing of Biotube. The biological response after Biotube implantation was histologically evaluated. The designed Biotubes (length: 50 cm, internal diameter: 4 mm, and wall thickness: 0.85 mm) were obtained by embedding molds on the backs of six goats for a predetermined period (1-5 months). The same goats underwent bypass surgery on the carotid arteries using Biotubes (average length: 12 cm). After implantation, echocardiography was used to periodically monitor patency and blood flow velocity. The maximum observation period was 6 months, and tissue analysis was conducted after graft removal, including the anastomosis. All molds generated Biotubes that exceeded the tensile strength of normal goat carotid arteries, and eight randomly selected Biotubes were implanted. Thrombotic occlusion occurred immediately postoperatively (1 tube) if anticoagulation was insufficient, and two tubes, with insufficient Biotube strength (<5 N), were ruptured within a week. Five tubes maintained patency for >2 months without aneurysm formation. The spots far from the anastomosis became stenosed within 3 months (3 tubes) when Biotubes had a wide intensity distribution, but the shape of the remaining two tubes remained unchanged for 6 months. The entire length of the bypass region was walled with an αSMA-positive cell layer, and an endothelial cell layer covered most of the lumen at 2 months. Complete endothelial laying of the luminal surface was obtained at 3 months after implantation, and a vascular wall structure similar to that of native blood vessels was formed, which was maintained even at 6 months. The stenosis was indicated to be caused by fibrin adhesion on the luminal surface, migration of repair macrophages, and granulation formation due to the overproliferation of αSMA-positive fibroblasts. We revealed the importance of Biotubes that are homogeneous, demonstrate a tensile strength > 5 N, and are implanted under appropriate antithrombotic conditions to achieve long-term patency of Biotube. Further, we clarified the Biotube regeneration process and the mechanism of stenosis. Finally, we obtained the necessary conditions for a confirmatory implant study planned shortly.

Hybrid Co‐Spinning and Melt Electrowriting Approach Enables Fabrication of Heterotypic Tubular Scaffolds Resembling the Non‐Linear Mechanical Properties of Human Blood Vessels

AbstractThe current barrier to clinical translation of small‐caliber tissue‐engineered vascular grafts (TEVGs) is the long‐term patency upon implantation in vivo. Key contributors are thrombosis and stenosis caused by inadequate mechanical graft properties and mismatch of hemodynamic conditions. Herein, the authors report on an approach for the fabrication of a mechanically tunable bilayered composite TEVGs. Using a combination of solution electrospinning (SES) and melt electrowriting (MEW), it is shown that the mechanical properties can be tailored and the natural J‐shape of the stress–strain relationship can be recapitulated. Upon cell seeding, the luminal surface of the composite SES layers permits the formation of a confluent mature endothelium. MEW fibers provide structural support to promote stacking and orientation of MSCs in a near‐circumferential native vessel like direction. By adjusting the ratios of poly(ε‐caprolactone) and poly(ester‐urethane) during the SES process, TEVGs with a range of tunable mechanical properties can be manufactured. Notably, this hybrid approach permits modulation of the radial tensile properties of TEVGs to approximate different native vessels. Overall, a strategy for the fabrication of TEVGs with mechanical properties resembling those of native vessels which can help to accommodate long‐term patency of TEVGs at various treatment sites in future applications is demonstrated.

Late In-Stent Restenosis of a Saphenous Vein Graft Treated with High-Pressure Balloon Dilatation and Drug Eluting Balloon Dilatation: Case Report

In the modern interventional treatment of degenerated saphenous vein grafts, the use of both bare metal and drug eluting stents have been described so far. Drug eluting balloons have been increasingly used in cases of in-stent restenosis and to some extent de novo stenosis of native coronary vessels. Based on pure logic approach, the use of drug eluting balloons in in-stent restenosis of the saphenous vein graft may be of great interest. Still, few high-quality data on this subject exist and no general recommendations can be made. This paper illustrates a typical case of a symptomatic late in-stent restenosis of a saphenous vein graft occurred 15 months after a percutaneous coronary intervention with implantation of two drug eluting stents. Intravascular ultrasound revealed a mixture of stent underexpansion and severe neointima. This was treated safely with a prolonged high pressure balloon dilatation followed by dilatation with a drug eluting balloon. The primary result was very good. During the intervention the patient remained asymptomatic and was discharged the next day on dual anti-platelet therapy. During the 10-month follow-up the patient remained asymptomatic. This case demonstrates the usefulness and clinical safety of drug eluting balloons in treating in-stent restenosis in the saphenous vein grafts.

Acute Aortic Stent Graft Thrombosis in Patient with Recent COVID-19 Infection

Although COVID-19 primarily affects the respiratory system, it can have various effects on other organs, including the cardiovascular system. COVID-19 can lead to a prothrombotic status, promoting blood clotting, which can potentially affect native vessels and implanted devices. The exact mechanisms through which it leads to increased clotting are not yet fully understood but may involve inflammation, endothelial dysfunction, and a hyperactive immune response. In the present report, we describe a case of acute aortic stent graft thrombosis four days after the resolution of SARS-CoV-2 infection. The patient required emergent explantation of the stent graft after the failure of endovascular bailout procedures.