Biology subjects

van der Laan, K. W. F.

Publications and source records attributed to van der Laan, K. W. F..

3 recordsLinked to original sources

bioRxiv2025

Linking arterial biomechanics, contractility, and microstructure: A novel platform for combined structure-function assessment in murine arteries under physiological conditions

BackgroundEx vivo characterization of arterial viscoelastic properties shows arterial stiffness and contractility to depend on both axial stretch and dynamic pressurization. While these arterial properties are the subject of extensive ex vivo research due to their relevance to vascular pathophysiology, only few experimental approaches mimic both physiological axial stretch and dynamic pressurization when characterizing arterial biomechanics, vasoreactivity, and tissue microstructure. To fill this gap, we developed a custom dynamic biaxial pressure myograph compatible with two-photon laser scanning microscopy (TPLSM). MethodsWe studied five murine carotid artery segments. Sample viscoelastic behaviour was characterized by quasi-static and dynamic pressurization experiments at and around physiological axial stretch, as well as quasi-static stretching at physiological pressures. In addition, vasoconstriction in response to 2 {micro}M phenylephrine was measured during dynamic pressurization and with axial loads that mimicked physiological conditions. Lastly, arterial collagen, elastin, and cell nuclei were imaged using TPLSM with the sample at physiological axial stretch and pressurized at 100 mmHg. ResultsThe setup enabled capture of the non-linear biaxial viscoelastic behaviour of the arterial wall as well as the viscoelastic stiffening with dynamic pressurization. Modulation of these characteristics upon stimulated smooth muscle contraction was also captured well. Moreover, the related ultrastructural properties of the collagen-elastin network as well as the transmural cell distribution, were recordable at corresponding loading conditions by TPLSM. ConclusionThe presented multi-modal characterization platform enables comprehensive ex vivo measurements under well-controlled in vivo-like loading conditions, for in-depth studies focusing on arterial stiffening. Our findings emphasize the need for controlling dynamic pressure and axial stretch conditions in investigating mechanistic and constitutive aspects of arterial stiffening.

bioengineering↗

bioRxiv2024

The MAASWERP study: An international, comparative case study on measuring biomechanics of the aged murine aorta

Arterial stiffening is a hallmark of vascular ageing, and unravelling its underlying mechanisms has become a central theme in the field of cardiovascular disease. While various techniques and experimental setups are accessible for investigating biomechanics of blood vessels both in vivo and ex vivo, comparing findings across diverse methodologies is challenging. In the present study, we aimed to compare arterial stiffness measurements of two distinct ex vivo setups for measuring aortic mechanics. First, we measured arterial stiffness in the aorta of adult (5 months) and aged (24 months) wild-type C57Bl/6J mice in vivo, after which ex vivo biomechanical evaluation was performed using the Rodent Oscillatory Tension Setup to study Arterial Compliance (ROTSAC; University of Antwerp, Belgium) and the DynamX setup (Maastricht University, The Netherlands). Measurements in both setups were conducted in parallel with matched protocols and identical buffers and chemicals. Overall, both methods revealed age-related increased stiffness, although parameters of aortic mechanics showed different numerical values, suggesting that results are not directly interchangeable between methods. Surprisingly, smooth muscle cell contraction had opposing effects between the setups. Indeed, smooth muscle cell contraction increased arterial stiffness in the ROTSAC but decreased stiffness in the DynamX. These opposing effects could be attributed to how the two setups differentially load the collagen fibres in the arterial wall, ex vivo. In conclusion, the observed differences between the two ex vivo setups highlight the necessity to report findings on (altered) aortic mechanics in the context of the used methodology.

bioengineering↗

bioRxiv2023

Evaluating flash freezing for preservation of rat abdominal aorta for delayed biomechanical characterization

Most studies investigating arterial stiffening use animal rather than human arteries. This is because human tissue becomes available in small amounts and at irregular times, which complicates planning of experimental work. Suitable tissue preservation methods for delayed biomechanical testing prevents the need for testing fresh tissue and alleviates some of the logistical challenges of human ex vivo studies. Therefore, the present study aimed to investigate whether the existing method of flash freezing and subsequent cryostorage provides is suitable for delaying the characterization of arterial biomechanics. Fresh and flash frozen abdominal aortas (n=16 and 14, respectively) were quasi- statically and dynamically tested using a biaxial testing set-up with dynamic pressurization capabilities. The acquired biomechanical data was modeled using a constituent-based quasi-linear viscoelastic modeling framework, deriving directional stiffness parameters, individual constituent biomechanical contributions, and viscoelastic stiffening under dynamic pressurization conditions. Flash freezing reduced arterial wall thickness, increased circumferential stiffness, as well as reduced viscoelastic stiffening at higher pressures. These findings reflected those in the modeled contribution of collagen to arterial biomechanics, showing increased collagen load bearing at higher pressures. However, despite the above mentioned detectable changes, flash freezing did not alter the mechanical relation between elastin and collagen, maintaining a non-linear response to pressurization and stretch. Flash freezing may thus be suitable for studies requiring delayed characterization of passive arterial biomechanics, assuming care is taken to ascert that the impact of flash freezing on study groups can be approached as a systematic error.

bioengineering↗