Establishment of a Modular Hemodynamic Simulator for Accurate In Vitro Simulation of Physiological and Pathological Pressure Waveforms in Native and Bioartificial Blood Vessels

Abstract

Purpose In vitro stimulation of native and bioartificial vessels in perfusable systems simulating natural mechanical environments of the human vasculature represents an emerging approach in cardiovascular research. Promising results have been achieved for applications in both regenerative medicine and etiopathogenetic investigations. However, accurate and reliable simulation of the wide variety of physiological and pathological pressure environments observed in different vessels still remains an unmet challenge. Methods We established a modular hemodynamic simulator (MHS) with interchangeable and modifiable components suitable for the perfusion of native porcine—(i.e. the aorta, brachial and radial arteries and the inferior vena cava) and bioartificial fibrin-based vessels with anatomical site specific pressure curves. Additionally, different pathological pressure waveforms associated with cardiovascular diseases including hyper- and hypotension, tachy- and bradycardia, aortic valve stenosis and insufficiency, heart failure, obstructive cardiomyopathy and arterial stiffening were simulated. Pressure curves, cyclic distension and shear stress were measured for each vessel and compared to ideal clinical pressure waveforms. Results The pressure waveforms obtained in the MHS showed high similarity to the ideal anatomical site specific pressure curves of different vessel types. Moreover, the system facilitated accurate emulation of physiological and different pathological pressure conditions in small diameter fibrin-based vessels. Conclusion The MHS serves as a variable in vitro platform for accurate emulation of physiological and pathological pressure environments in biological probes. Potential applications of the system include bioartificial vessel maturation in cardiovascular tissue engineering approaches as well as etiopathogenetic investigations of various cardiovascular pathologies.

An encapsulated fibrin‐based bioartificial tissue construct with integrated macrovessels, microchannels, and capillary tubes

“…These free‐standing segments are needed to enable easy and quick vascular anastomoses in the potential target organism. Therefore, fibrin grafts have been shown to be of sufficient mechanical strength to withstand physiological and supraphysiological pressures even without structural support of surrounding tissue (Helms, Haverich, et al, 2021; Helms, Lau, et al, 2021).…”

“…With the integration of the desired cell types (i.e., pancreatic β‐cells, smooth muscle cells, and hepatocytes), the matrix can be useful in various fields of organ engineering. Nonetheless, future studies are needed to verify seeding capacity for different cell types, generate a hierarchically organized interconnection between microchannels and capillary‐like tubes and to assess the performance of the patch after implantation in vivo (Helms, Haverich, et al, 2021).…”

3D Tissue-Engineered Vascular Drug Screening Platforms: Promise and Considerations

“…The pulsatile circulation was controlled with a left ventricular model, and the system allowed the control of dynamic flow, pressure waveforms, heart rate, and systolic fraction to match the physiological conditions of fetal or adult arteries or veins (220). Helms et al developed a modular hemodynamic simulator which allowed the exposure of fibrin blood vessels to site specific pressure curves, and allowed the simulation of physiological and pathological pressure conditions for small caliber vessels (213).…”

“…This demonstrated that the elimination of the anesthesia step, which is essential in animal studies, allows for a more accurate hemodynamically-equivalent model. Modular hemodynamic simulator which allowed the exposure of fibrin blood vessels to site specific pressure curves, and allowed the simulation of physiological and pathological pressure conditions for small caliber vessels (213) (191). The endothelium layer was stimulated with TNF-α or LDL and monocytes were then perfused into the system.…”

“…(B)hemodynamically-equivalent model. Modular hemodynamic simulator which allowed the exposure of fibrin blood vessels to site specific pressure curves, and allowed the simulation of physiological and pathological pressure conditions for small caliber vessels(213).Figure adapted from Helms et al (213) [Copyright © 2021, The Author(s), licensed under Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/]. (C) Drug testing.…”