Investigating 3D Printed Biomodels in Experimental Blood Flow Studies

Investigating 3D Printed Biomodels in Experimental Blood Flow Studies

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There are many applications for 3D printing in the biomedical research community, such as lab-on-a-chip tools, surgical planning, and drug delivery. Yet another is 3D biomodels, which is the focus of a study, titled “Low Cost 3D printed biomodels for biofluid mechanics applications,” published by a group of Portuguese researchers from the University of Minho and the Polytechnic Institute of Bragança. Carlos L. Faria, Diana Pinho, Jorge Santos, Luís M. Gonçalves, and Rui Lima discussed the fabrication of 3D biomodels for use in hemodynamic (relating to the flow of blood within the body’s organs and tissues) experimental flow studies.

The abstract states, “This paper shows the ability of the desktop 3D printers (also known as low cost 3D printers) to produce 3D biomodels able to be used on hemodynamic experimental flow studies. Overall, this paper shows that Fused Deposition Modelling (FDM) process combined with polydimethylsiloxane (PDMS) replication molding is a promising way to produce affordable biomedical devices to perform hemodynamic studies at both macro and micro scale levels.”

Biomodels are devices – physical or virtual – that replicate the form or geometry of a biological structure, like an artery. They can be used to perform in vitro and numerical experiments, and for their paper, the researchers presented an overview of successful polydimethylsiloxane (PDMS) biomodels made on desktop 3D printers, combined with PDMS replication molding, in order to complete in vitro blood flow studies at the microscale  and macroscale levels.

Fig. 1 3D printers used to make macro models: (a) Zprinter 310 Plus (b) Big Builder and (c) Cube 3D

The team tested three different 3D printers to perform micro and macro flow studies. Macro models of human carotid arteries were initially built on the Zprinter 310 Plus, but the team later switched to the extrusion-based systems of the Big Builder and Cube 3D.

“The intracranial aneurysm model and the 3D models of the micro devices were fabricated by depositing the thermoplastic material acrylonitrile butadiene styrene (ABS) on a stage layer-by-layer trough an extrusion nozzle,” the researchers wrote. “The advantages of this method are the low cost, the speed, and the ability to apply different kinds of thermoplastic materials, such as the ABS, polylactic acid (PLA), and nylon.”

CT (TC) scans were used to 3D print (TDP) the human carotid artery geometry for the PDMS models in the macro flow studies. Scan IP software was used to segment the TC images, and the file was converted to an STL. The 3D printed models were then put inside a molding box, and the biocompatible PDMS was poured over the master mold and cured. After it cooled, the model was removed from the mold box “where the inlet and outlet tubes were connected.”

“For the case of the PDMS microfluidic devices (dimensions from 5 mm down to 0.3 mm) to perform flow studies at micro scale level, the 3D models were obtained by the FDM process combined by PDMS replication molding,” the team explained. “The PDMS (Sylgard® 186, Dow Corning) was prepared also by mixing the prepolymer with the curing agent at 10:1 ratio and poured onto the printed models placed in the bottom of a petri dish and cured in an oven at 80 °C for 20 minutes. In parallel, another mixture of PDMS (20:1 ratio) was spin coated at 5000 rpm for 2 minutes (VTC-100 Vacuum Spin Coater) over a glass slide and cured in an oven at 80 °C for 20 minutes. By using a blade, the micro channels were cut off and the inlet/outlet holes of the fluid were done by using a fluid-dispensing tip. Finally, the channels were sealed by using the coated glass slide. Note that, to achieve a strong adhesion of the materials, the device was placed inside the oven at 80 °C for 24 h.”

Fig. 2 3D printed models and PDMS transparent flow channels

The team then presented an overview of work by other researchers focused on using PDMS 3D models for macro flow studies, such as 3D printed carotid artery models with and without aneurysms and a wall expansion assessment of an FDM 3D printed intracranial aneurysm model.

“The PDMS transparent models obtained from the 3D models fabricated by the TDP technique have shown to be a promising way to perform in vitro blood flow studies through anatomically realistic replica of a human carotid artery with and without aneurisms,” they explained about the former study.

“A promising approach to understand the mechanical behavior of aneurysms is by measuring the deformability of the walls by means of optical techniques,” they continued about the latter study.

“Pinho et al. [16] have developed a methodology able to measure experimentally the displacement field of an in vitro intracranial aneurysm model. This method is a combination of aneurysm in vitro models fabricated in PDMS…and the use of an Electronic Speckle Pattern Interferometry (ESPI) technique.”

This second study showed that wall thickness is important in terms of initiating aneurysm growth and later rupture, and that 3D printing can help validate numerical simulations of aneurysms, and find more details about what causes ruptures.

Fig. 5 (a) Model drawn in the Solidworks CAD software and dimensions tested in this study, and (b) microdevice master models 3D printed in the Big Builder and Cube 3D printers

The researchers also discussed several experimental in vitro micro blood flow studies, using 3D printed microdevices, that have taken place to provide a better understanding of the blood flow phenomena in microvessels and biomedical microdevices. They noted that a soft lithography method with expensive equipment is the most common way to make microfluidic devices, which is why it’s “important to explore low cost fabrication techniques.”

“The desktop 3D printers have shown potential to fabricate channels around 1mm, however few works have explored the ability of the low cost 3D printers to fabricate microfluidic devices,” they wrote. “In the present work we have tested the fabrication of several microchannels down to 0.3 mm by using two different desktop printers based on the FDM process.”

They 3D printed several ABS master models of microchannels to perform in vitro blood flow studies, and also made PDMS flow devices from the 3D printed master molds to investigate the cell-free layer (CFL) blood flow phenomenon that occurs during micro circulation.

“From the results obtained from all the tested PDMS flow devices we have only observed a clear CFL at the PDMS devices fabricated by the Cube 3D printer with a height of 0.1 mm. Fig.6 shows clearly that at a height of 0.1 mm there is a tendency to generate a cell depleted region around the wall of the microchannel,” the researchers wrote. “In contrast, this tendency was not observed for the heights of 0.5 and 1 mm. Although, these results have demonstrated that is possible to have the formation of a CFL within the microchannels produced by the Cube 3D printer, the width of the flow channels need to be further reduced in order to obtain a cross section with a geometry more close to real microvessels.”

Fig. 6 In vitro blood flow visualizations at PDMS microfluidic devices fabricated by the Cube 3D printer

The team is pleased with the “extremely encouraging” results they got from the 3D printed devices combined with PDMS molds.

“We believe that this combination is a promising technique to perform more realistic in vitro blood studies through anatomical models and consequently improve our current understanding of the origin and development of cardiovascular diseases,” they concluded.

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September 3, 2019 at 02:51AM