Background: Although tunneled dialysis catheters (TDC) are far from ideal, they still represent the main form of vascular access for most patients beginning dialysis. Catheters are easy to place and allow patients instant access to dialysis, but regardless of these benefits, catheters are associated with a high incidence of significant complications like bloodstream infections, central venous stenosis, thrombosis, and dysfunction. In the present study, we aim to describe and characterize a swine model of catheter dysfunction and bloodstream infection, that recreates the clinical scenario, to help to serve as a platform to develop therapeutic innovations for this important clinical problem. Methods: Six Yorkshire cross pigs were used in this study. Non-coated commercial catheters were implanted in the external jugular recreating the main features of common clinical practice. Catheters were aseptically accessed twice a week for a mock dialysis procedure (flushing in and out) to assess for and identify catheter dysfunction. Animals were monitored daily for infections; once detected, blood samples were collected for bacterial culture and antibiograms. Study animals were euthanized when nonresponsive to treatment. Tissue samples were collected in a standardized fashion for macroscopic inspection and histological analysis. Results: The data analysis revealed an early onset of infection with a median time to infection of 9 days, 40% of the isolates were polymicrobial, and the average time to euthanasia was 20.16 ± 7.3 days. Median time to catheter dysfunction onset was 6 days post-implantation. Postmortem dissection revealed external fibrin sheath and internal thrombosis as the main causes of catheter dysfunction. There was also evidence of central venous stenosis with positive cells for αSMA, CD68, Ki67, Smoothelin, and Vimentin within the venous neointima. Conclusions: The described model represents a reliable and reproducible large animal model of catheter dysfunction and bloodstream infection, which recreates all the main complications of TDC’s and so could be used as a validated large animal model to develop new therapies for TDC related infection, thrombosis/dysfunction and central venous stenosis.

Advancements in laboratory animal training increasingly incorporate technological innovations aiming to better align training standards with the 3Rs (Replacement, Reduction, and Refinement). This trend is shifting away from traditional reliance on live animals and cadavers toward simulation-based methods. This study introduces and assesses the validity of a novel 3D-printed rodent surgical simulator designed for the practice and training of basic rodent surgical skills. To evaluate its potential to partially replace animal use, refine rodent surgical training, and reduce the number of animals needed, a multicenter validation study across 5 European and US research academic centers was conducted. The study assessed the simulator’s face, content, and construct validity, involving participants inexperienced and experts in rodent surgery. The construct validity was evaluated through task completion times and blinded quality assessments across multiple training iterations. The results revealed that inexperienced participants demonstrated significant improvements in both speed and quality of surgical tasks with repeated simulator use, eventually reaching performance levels comparable to experts’ initial attempts. Expert participants consistently outperformed the inexperienced group. Face and content validity were supported by postuse surveys, with high ratings from both groups regarding the simulator’s anatomic realism and its perceived usefulness for the acquisition and development of fundamental surgical skills. Overall, the findings of this study support that this 3D-printed rodent surgical simulator offers a realistic, effective, and ethically sound alternative for basic rodent surgical skills training and competency assessment.

The arteriovenous fistula (AVF) is the preferred method of vascular access for hemodialysis; however, 30–50% of AVFs undergo primary maturation failure and are unsuitable for clinical use. As disturbed hemodynamics initiate endothelial injury and intimal hyperplasia, we designed an endovascular flow-conditioning anastomotic device (FCAD) to directly improve AVF hemodynamics and protect the anastomotic region. Using computational fluid dynamics, we characterized the flow field and wall shear stress (WSS) profiles in idealized AVF models with and without the FCAD. Incorporation of the FCAD into a brachiocephalic AVF model reduced regions of oscillatory WSS and generated a symmetrical flow profile in the draining vein compared to a reference AVF. Parametric studies identified an FCAD geometry with a tab angle, height, and aspect ratio of 30°, 0.1 diameters, and 1.0 that increased time-averaged WSS along the inner venous wall and achieved a physiological WSS (1–3 Pa) without inducing regions of oscillatory flow throughout the cardiac cycle. Similar findings were observed with an in vitro model using particle image velocimetry. This study demonstrates the feasibility of the FCAD to normalize venous flow and WSS while imposing minimal resistance to blood flow. Restoring physiological WSS levels on the venous wall may help preserve endothelial function and improve AVF maturation.

The arteriovenous fistula (AVF) is the preferred method of vascular access for hemodialysis; however, 30-50% of AVFs undergo primary failure and are unsuitable for clinical use. As disturbed hemodynamics initiate endothelial injury and intimal hyperplasia, we designed an endovascular flow-conditioning anastomotic device (FCAD) to directly improve AVF hemodynamics and protect the anastomotic region. Using computational fluid dynamics, we characterized the flow field and wall shear stress (WSS) profiles in idealized AVF models with and without the FCAD. Incorporation of the FCAD into a brachiocephalic AVF model reduced regions of oscillatory WSS and generated a symmetrical flow profile in the draining vein compared to a reference AVF. Parametric studies also identified an FCAD geometry with a tab angle of 30 degrees, a height of 0.1 diameters, and an aspect ratio of 1.0 that restored time-averaged WSS along the inner venous wall, achieving a physiological level without inducing regions of oscillatory flow throughout the cardiac cycle. Similar findings were observed with an in vitro model using particle imaging velocimetry. This study demonstrates the feasibility of the FCAD to normalize venous flow and WSS while imposing minimal resistance to blood flow. Restoring physiological WSS levels on the venous wall is expected to preserve endothelial function and improve AVF maturation.