PMID- 28717801
OWN - NLM
STAT- MEDLINE
DCOM- 20180806
LR  - 20220129
IS  - 1473-0189 (Electronic)
IS  - 1473-0189 (Linking)
VI  - 17
IP  - 16
DP  - 2017 Aug 8
TI  - Mimicking arterial thrombosis in a 3D-printed microfluidic in vitro vascular 
      model based on computed tomography angiography data.
PG  - 2785-2792
LID - 10.1039/c7lc00202e [doi]
AB  - Arterial thrombosis is the main instigating factor of heart attacks and strokes, 
      which result in over 14 million deaths worldwide every year. The mechanism of 
      thrombosis involves factors from the blood and the vessel wall, and it also 
      relies strongly on 3D vessel geometry and local blood flow patterns. Microfluidic 
      chip-based vascular models allow controlled in vitro studies of the interaction 
      between vessel wall and blood in thrombosis, but until now, they could not fully 
      recapitulate the 3D geometry and blood flow patterns of real-life healthy or 
      diseased arteries. Here we present a method for fabricating microfluidic chips 
      containing miniaturized vascular structures that closely mimic architectures 
      found in both healthy and stenotic blood vessels. By applying stereolithography 
      (SLA) 3D printing of computed tomography angiography (CTA) data, 3D vessel 
      constructs were produced with diameters of 400 mum, and resolution as low as 25 
      mum. The 3D-printed templates in turn were used as moulds for polydimethylsiloxane 
      (PDMS)-based soft lithography to create microfluidic chips containing 
      miniaturized replicates of in vivo vessel geometries. By applying computational 
      fluid dynamics (CFD) modeling a correlation in terms of flow fields and local 
      wall shear rate was found between the original and miniaturized artery. The walls 
      of the microfluidic chips were coated with human umbilical vein endothelial cells 
      (HUVECs) which formed a confluent monolayer as confirmed by confocal fluorescence 
      microscopy. The endothelialised microfluidic devices, with healthy and stenotic 
      geometries, were perfused with human whole blood with fluorescently labeled 
      platelets at physiologically relevant shear rates. After 15 minutes of perfusion 
      the healthy geometries showed no sign of thrombosis, while the stenotic 
      geometries did induce thrombosis at and downstream of the stenotic area. Overall, 
      the novel methodology reported here, overcomes important design limitations found 
      in typical 2D wafer-based soft lithography microfabrication techniques and shows 
      great potential for controlled studies of the role of 3D vessel geometries and 
      blood flow patterns in arterial thrombosis.
FAU - Costa, Pedro F
AU  - Costa PF
AD  - Utrecht Biofabrication Facility, Utrecht University, Uppsalalaan 8, 3584 CT 
      Utrecht, The Netherlands.
FAU - Albers, Hugo J
AU  - Albers HJ
FAU - Linssen, John E A
AU  - Linssen JEA
FAU - Middelkamp, Heleen H T
AU  - Middelkamp HHT
FAU - van der Hout, Linda
AU  - van der Hout L
FAU - Passier, Robert
AU  - Passier R
FAU - van den Berg, Albert
AU  - van den Berg A
FAU - Malda, Jos
AU  - Malda J
FAU - van der Meer, Andries D
AU  - van der Meer AD
LA  - eng
GR  - 647426/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Lab Chip
JT  - Lab on a chip
JID - 101128948
SB  - IM
MH  - Cell Culture Techniques
MH  - Cell Line
MH  - *Computed Tomography Angiography
MH  - Equipment Design
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - *Lab-On-A-Chip Devices
MH  - *Models, Cardiovascular
MH  - Printing, Three-Dimensional
MH  - *Thrombosis
EDAT- 2017/07/19 06:00
MHDA- 2018/08/07 06:00
CRDT- 2017/07/19 06:00
PHST- 2017/07/19 06:00 [pubmed]
PHST- 2018/08/07 06:00 [medline]
PHST- 2017/07/19 06:00 [entrez]
AID - 10.1039/c7lc00202e [doi]
PST - ppublish
SO  - Lab Chip. 2017 Aug 8;17(16):2785-2792. doi: 10.1039/c7lc00202e.