Background The disturbed flow contributes to juxta-anastomotic intimal hyperplasia (IH) in arteriovenous fistulas (AVFs). This study developed an in vitro method aiming to understand the hemodynamic impact on endothelial cells (ECs) in AVFs. Methods A tubular bifurcation AVF model was constructed, and the disturbed flow was induced near the bifurcation by pulsatile flow. Hemodynamics was simulated using computational fluid dynamics (CFD) and visualized as 2D contour plots. Human Umbilical Vein Endothelial Cells (HUVECs) were cultured on a tailored polycarbonate membrane (PCM) and placed in the model. HUVECs on the PCM allowed precise mapping to the hemodynamic plots. Results CFD identified four regions: the outer wall with high time-averaged wall shear stress (TAWSS MAX) and transverse wall shear stress (TransWSS MAX), the inner wall with low and oscillatory wall shear stress (L/O), and the pulsatile flow (PF). HUVECs in PF were aligned in the direction of flow. The cells in other regions showed more focal adhesion junctions and fewer glycocalyces. HUVECs on inner wall had the lowest expression of Krüppel-like factor 2 and endothelial nitric oxide synthase, while the outer wall showed the highest expression of platelet-derived growth factor and transforming growth factor-β. Conclusions We developed an in vitro AVF model and validated the effects of different hemodynamic profiles on ECs by matching CFD plots with cell positions on a tailored PCM. This study shows that the in vitro AVF model can be a promising tool to assess the impact of interventions aimed at improving ECs function in AVFs. Statement of Significance In Vitro Model Development : An innovative in vitro model was developed to simulate arteriovenous fistula conditions, allowing for direct assessment of endothelial cell behavior under varied hemodynamic conditions. Linking Hemodynamics to Cell Response : The research successfully correlated computational fluid dynamics results with specific endothelial cell positions, facilitating a clearer understanding of the impact of hemodynamics on cell morphology and function. Arteriovenous Fistula Failure Understanding : The study enhances the understanding of arteriovenous fistula failure mechanisms, specifically the role of intimal hyperplasia caused by disturbed flow.

Arteriovenous fistulas and arteriovenous grafts are the most commonly used vascular access for hemodialysis in patients with end-stage chronic kidney disease. However, both methods face significant challenges due to the hemodynamic disturbances induced by the arteriovenous anastomosis. This causes changes in vascular structure and blood flow velocity near the anastomosis site after the fistula/graft surgery, and introduces abnormal wall shear stress and cyclic stretch. This leads to endothelial cell dysfunction, vascular smooth muscle cell proliferation, and adverse remodeling. The resulting effects include low patency rates due to vascular stenosis caused by intimal hyperplasia and insufficient outward remodeling. Additionally, the high flow conduit has been linked to adverse cardiac remodeling. To address this, various strategies have been explored to correct these localized hemodynamic abnormalities, aiming to improve long-term patency rates. In this review, an overview is provided of the current surgical techniques, anastomosis types, anastomosis angles, external scaffolds, modified fistula designs, and types of grafts. It evaluates the impact of these approaches on local hemodynamics in the access conduit and their potential effects on patient outcomes.

Objective: Central venous catheters (CVCs) provide direct access to the central circulatory system, commonly used in hemodialysis and intensive care units for drug administration. Although uncertified for the procedure, CVCs are sometimes used for power injection of contrast medium (CM) during CT scans to avoid peripheral intravenous catheter placement. Previous studies suggest this practice is safe, but incidents are reported. This study aims to measure intraluminal pressure during CM injection through CVCs and assess its impact on the luminal surface to guide responsible clinical use. Materials and methods: An experimental in vitro test setup was developed. Four samples each of three different types of unused CVCs were used. Strain gauges were applied to the exterior walls of either the inflow or outflow lumen of the CVC. These gauges measured material deformation due to intraluminal pressure during CM injections at rates of 4.5 and 8 mL/s, each performed five times. Strain data were calibrated against known pressures in a static system. Three CVCs of each type were then pressurized until bursting, and one was subjected to microscopic analysis of the luminal surfaces. Results: Intraluminal pressures measured (97–545 kPa or 14–79 PSI) were below the burst pressure (779–1248 kPa or 113–181 PSI) in all instances. Strain regression analysis shows a statistically significant (p < 0.01) trend over 10 injections in all CVCs tested except one, indicating material fatigue. Surface microscopy revealed surface micro-cracks from repeated injections, suggesting material damage. Conclusions: The intraluminal pressures from power injections of CM are sufficiently low to prevent CVC bursting. While incidental use for CM injection appears safe, repeated use may cause material damage.

Disturbed flow is one of the pathological initiators of endothelial dysfunction in intimal hyperplasia (IH) which is commonly seen in vascular bypass grafts, and arteriovenous fistulas. Various in vitro disease models have been designed to simulate the hemodynamic conditions found in the vasculature. Nonetheless, prior investigations have encountered challenges in establishing a robust disturbed flow model, primarily attributed to the complex bifurcated geometries and distinctive flow dynamics. In the present study, we aim to address this gap by introducing an in vitro bypass flow model capable of inducing disturbed flow and other hemodynamics patterns through a pulsatile flow in the same model. To assess the model's validity, we employed computational fluid dynamics (CFD) to simulate hemodynamics and compared the morphology and functions of human umbilical venous endothelial cells (HUVECs) under disturbed flow conditions to those in physiological flow or stagnant conditions. CFD analysis revealed the generation of disturbed flow within the model, pinpointing the specific location in the channel where the effects of disturbed flow were observed. High-content screening, a single-cell morphological profile assessment, demonstrated that HUVECs in the disturbed flow area exhibited random orientation, and morphological features were significantly distinct compared to cells in the physiological flow or stagnant condition after a two days of flow exposure. Furthermore, HUVECs exposed to disturbed flow underwent extensive remodeling of the adherens junctions and expressed higher levels of endothelial cell activation markers compared to other hemodynamic conditions. In conclusion, our in vitro bypass flow model provides a robust platform for investigating the associations between disturbed flow pattern and vascular diseases.

Objective: Hemodialysis patients usually receive an arteriovenous fistula (AVF) in the arm as vascular access conduit to allow dialysis 2-3 times a week. This AVF introduces the high flow necessary for dialysis, but over time the ever-present supraphysiological flow is the leading cause of complications. This study aims to develop an implantable device able to non-invasively remove the high flow outside dialysis sessions. Methods: The developed prototype features a magnetic ring allowing external coupling and torque transmission to non-invasively control an AVF valve. Mock-up devices were implanted into arm and sheep cadavers to test sizes and locations. The transmission torque, output force, and valve closure are measured for different representative skin thicknesses. Results: The prototype was placed successfully into arm and sheep cadavers. In the prototype, a maximum output force of 78.9 ± 4.2 N, 46.7 ± 1.9 N, 25.6 ± 0.7 N, 13.5 ± 0.6 N and 6.3 ± 0.4 N could be achieved non-invasively through skin thicknesses of 1-5 mm respectively. The fistula was fully collapsible in every measurement through skin thickness up to the required 4 mm. Conclusion: The prototype satisfies the design requirements. It is fully implantable and allows closure and control of an AVF through non-invasive torque transmission. In vivo studies are pivotal in assessing functionality and understanding systemic effects. Significance: A method is introduced to transfer large amounts of energy to a medical implant for actuation of a mechanical valve trough a closed surface. This system allows non-invasive control of an AVF to reduce complications related to the permanent high flow in conventional AVFs.

Introduction: The recent introduction of the European Medical Device Regulation poses stricter legislation for manufacturers developing medical devices in the EU. Many devices have been placed into a higher risk category, thus requiring more data before market approval, and a much larger focus has been placed on safety. For implantable and Class III devices, the highest risk class, clinical evidence is a necessity. However, the requirements of clinical study design and developmental outcomes are only described in general terms due to the diversity of devices. Methods: A structured approach to determining the requirements for the clinical development of high-risk medical devices is introduced, utilizing the question-based development framework, which is already used for pharmaceutical drug development. An example of a novel implantable device for haemodialysis demonstrates how to set up a relevant target product profile defining the device requirements and criteria. The framework can be used in the medical device design phase to define specific questions to be answered during the ensuing clinical development, based upon five general questions, specified by the question-based framework. Results: The result is a clear and evaluable overview of requirements and methodologies to verify and track these requirements in the clinical development phase. Development organizations will be guided to the optimal route, also to abandon projects destined for failure early on to minimize development risks. Conclusion: The framework could facilitate communication with funding agencies, regulators and clinicians, while highlighting remaining ‘known unknowns’ that require answering in the post-market phase after sufficient benefit is established relative to the risks.