The cannulation of blood vessels is one of the most basic and essential interventions in medical practice. A common adverse event of this procedure is miscannulation with infiltration of the second... Show moreThe cannulation of blood vessels is one of the most basic and essential interventions in medical practice. A common adverse event of this procedure is miscannulation with infiltration of the second part of the vessel wall, often resulting in a perivascular hematoma. In hemodialysis patients, surgically created arteriovenous conduits are cannulated 3-4 times per week to provide sufficient blood supply to the hemodialysis machine. However, the high blood flow and pressure in these vascular access sites increase the risk of complications upon miscannulation. A novel needle system that allows for rapid automatic retraction of the needle in response to contact with blood after positioning the cannula in the blood vessel was developed to reduce the risk of miscannulation. The device can easily be incorporated into existing needle designs. The mechanical functionality of the device was validated by testing prototypes in an ex vivo system. Optimization of the needle system was performed to enhance response time and piston shape. A final prototype design was manufactured and validated. The optimal membrane composition and piston shape were determined, which resulted in a needle response time of 40 ms upon contact with fluid at a pressure of 100 mmHg (arterial pressure). Here, we have successfully designed, mechanically validated, and tested a novel automated rapid needle retraction system that allows incorporation into existing needle systems. This device could notably decrease the difficulty of vessel cannulation and the prevalence of hematoma formation. Show less
The durability of prosthetic arteriovenous (AV) grafts for hemodialysis access is low, predominantly due to stenotic lesions in the venous outflow tract and infectious complications. Tissue... Show moreThe durability of prosthetic arteriovenous (AV) grafts for hemodialysis access is low, predominantly due to stenotic lesions in the venous outflow tract and infectious complications. Tissue engineered blood vessels (TEBVs) might offer a tailor-made autologous alternative for prosthetic grafts. We have designed a method in which TEBVs are grown in vivo, by utilizing the foreign body response to subcutaneously implanted polymeric rods in goats, resulting in the formation of an autologous fibrocellular tissue capsule (TC). One month after implantation, the polymeric rod is extracted, whereupon TCs (length 6 cm, diameter 6.8 mm) were grafted as arteriovenous conduit between the carotid artery and jugular vein of the same goats. At time of grafting, the TCs were shown to have sufficient mechanical strength in terms of bursting pressure (2382 +/- 129 mmHg), and suture retention strength (SRS: 1.97 +/- 0.49 N). The AV grafts were harvested at 1 or 2 months after grafting. In an ex vivo whole blood perfusion system, the lumen of the vascular grafts was shown to be less thrombogenic compared to the initial TCs and ePTFE grafts. At 8 weeks after grafting, the entire graft was covered with an endothelial layer and abundant elastin expression was present throughout the graft. Patency at 1 and 2 months was comparable with ePTFE AV-grafts. In conclusion, we demonstrate the remodeling capacity of cellularized in vivo engineered TEBVs, and their potential as autologous alternative for prosthetic vascular grafts. Show less
In the evaluation of tissue-engineered blood vessels (TEBVs), the utilization of the correct mechanical test to assess the burst pressure is pivotal for translation to a clinical setting. The ISO... Show moreIn the evaluation of tissue-engineered blood vessels (TEBVs), the utilization of the correct mechanical test to assess the burst pressure is pivotal for translation to a clinical setting. The ISO 7198 standard outlines various methods that may be implemented to evaluate the mechanical characteristics of vascular prosthetics. The gold standard is the direct measurement of the pressurized burst pressure. Two alternative indirect methods are the circumferential tensile strength (CTS) and the probe burst pressure. There are limited data validating the use of the indirect methods for their predictive capacity of the pressurized burst pressure in single biological vessel samples. We assess the two indirect methods compared with the direct pressurized burst pressure measurement, for their correlation within single biological samples, using methods presently used in literature and as they are proposed by the ISO 7198. The CTS, the probe burst pressure, and the pressurized burst pressure correlated very well (All R-2 > 0.89) when silicone samples were assessed, although the indirect methods resulted in a large overestimation of the burst pressure. The correlation between the three mechanical tests was poor (all R-2 <0.18) when arterial and venous samples were investigated. Freezing and subsequent thawing before testing had no impact on the mechanical properties of the vessels. Strain rates within the strain rate window provided by the ISO 7198 (50-200 mm/min), likewise, had no impact on the outcome of the tests. Neither the CTS nor the probe burst pressure is predictive of the pressurized burst pressure of the biological vascular tissue. Unless explicitly validated in a testing system on a range of biological tissues, the derived methods should not be utilized for the evaluation of the burst pressure of biological TEBVs for clinical purposes. Impact Statement Vascular tissue engineering (VTE) is a rapidly expanding field, with numerous approaches being explored both in preclinical and clinical settings. A pivotal factor in the development of VTE techniques is patient safety, notably with respect to the mechanical properties of the vessels. Of the mechanical properties, the bursting strength, representing the ability of a vessel to withstand the forces exerted on it by blood pressure, is the most important. The burst pressure is commonly assessed using one of three methods proposed by the ISO 7198. In this study, we evaluate the three burst pressure assessment methods exactly as they are presently in the field of VTE. We show that the indirect assessment methods, as they are presently used, provide inconsistent and therefore unreliable estimates of the true yield stress of a vessel. Show less
Vascular access is the lifeline for patients on hemodialysis. Arteriovenous fistulas (AVFs) are the preferred vascular access, but AVF maturation failure remains a significant clinical problem.... Show moreVascular access is the lifeline for patients on hemodialysis. Arteriovenous fistulas (AVFs) are the preferred vascular access, but AVF maturation failure remains a significant clinical problem. Currently, there are no effective therapies available to prevent or treat AVF maturation failure. AVF maturation failure frequently results from venous stenosis at the AVF anastomosis, which is secondary to poor outward vascular remodeling and excessive venous intimal hyperplasia that narrows the AVF lumen. Arteriovenous grafts (AVGs) are the next preferred vascular access when an AVF creation is not possible. AVG failure is primarily the result of venous stenosis at the vein-graft anastomosis, which originates from intimal hyperplasia development. Although there has been advancement in our knowledge of the pathophysiology of AVF maturation and AVG failure, this has not translated into effective therapies for these two important clinical problems. Further work will be required to dissect out the mechanisms of AVF maturation failure and AVG failure to develop more specific therapies. This review highlights the major recent advancements in AVF and AVG biology, reviews major clinical trials, and discusses new areas for future research. Show less
