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
Hadavi, E.; Leijten, J.; Engelse, M.; Koning, E. de; Jonkheijm, P.; Karperien, M.; Apeldoorn, A. van 2019
Intrahepatic islet transplantation is a promising therapy for treatment of type 1 diabetes. During islet isolation, collagenase is used to extract islets from the pancreas, leading to loss of... Show moreIntrahepatic islet transplantation is a promising therapy for treatment of type 1 diabetes. During islet isolation, collagenase is used to extract islets from the pancreas, leading to loss of important cell-matrix interactions. Loss of the native pancreatic microenvironment is associated with apoptosis of islet cells, early graft failure, and poor islet function. The islet extracellular matrix (ECM) is composed of a specific combination of collagen (Col), laminin (LN), and fibronectin (FN) molecules. Reintroducing these molecules has been shown to boost the function, viability, morphology, and proliferation of beta-cells. In this research, the effect of combinatorial ECM on islet function and survival was investigated. Specifically, thin-film microwell array scaffolds made from two distinct biomaterials were coated with FN, collagen type IV (Col4), LN111, LN332, or a combination thereof. We found that coatings containing a single type of ECM molecule, for example, FN or Col, can improve short-term islet function. However, these single proteins do not prevent loss of morphology and subsequent loss of islet function afterward. In contrast, combining Col4 with LN111 at a ratio of 8:2 not only improved short-term islet function but also preserved islet structure and islet function on a longer term. This effect was reproducibly shown on poly(ester-urethane) and poly(ethylene-glycol-terephthalate-poly(butylene-terephthalate) microwell islet delivery devices as well as tissue culture polystyrene. We concluded that biofunctionalization of inert biomaterials regardless of their molecular composition with a specific combination of islet ECM molecules can support and improve islet function over longer time periods. Our data suggested that creating a biomimetic islet niche by biofunctionalization of biomaterials can significantly improve the endocrine function of beta-cells. The creation of islet mimicking niches in islet delivery devices leads to an improvement of islet function by restoring part of the islet's ECM in these devices. Impact Statement This research deals with finding a proper bioengineering strategy to improve the outcome of islets transplantation for treatment of type 1 diabetes. It is focused on the mimicking of islet extracellular matrix niche in microwell islet delivery devices to improve their endocrine function. Show less
