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. 2018 Mar 1:69:26-33.
doi: 10.1016/j.jbiomech.2018.01.014. Epub 2018 Jan 16.

Original article submission: Platelet stress accumulation analysis to predict thrombogenicity of an artificial kidney

Amanda K W Buck  1 , Steven G Goebel  2 , Mark S Goodin  2 , Nathan J Wright  3 , Joseph J Groszek  4 , Jarrett Moyer  5 , Sukhveer Singh  5 , Danny Bluestein  6 , William H Fissell  4 , Shuvo Roy  7
Affiliations

Original article submission: Platelet stress accumulation analysis to predict thrombogenicity of an artificial kidney

Amanda K W Buck et al. J Biomech. .

Abstract

An implantable artificial kidney using a hemofilter constructed from an array of silicon membranes to provide ultrafiltration requires a suitable blood flow path to ensure stable operation in vivo. Two types of flow paths distributing blood to the array of membranes were evaluated: parallel and serpentine. Computational fluid dynamics (CFD) simulations were used to guide the development of the blood flow paths. Pressure data from animal tests were used to obtain pulsatile flow conditions imposed in the transient simulations. A key consideration for stable operation in vivo is limiting platelet stress accumulation to avoid platelet activation and thrombus formation. Platelet stress exposure was evaluated by CFD particle tracking methods through the devices to provide distributions of platelet stress accumulation. The distributions of stress accumulation over the duration of a platelet lifetime for each device revealed that stress accumulation for the serpentine flow path exceeded levels expected to cause platelet activation while the accumulated stress for the parallel flow path was below expected activation levels.

Keywords: Artificial kidney; Hemodynamics; Platelet stress accumulation; Thrombogenicity.

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Conflict of interest statement

Conflict of Interest Statement: Drs. Fissell and Roy have ownership in Silicon Kidney. Co-authors Buck, Goebel, Goodin, Wright, Groszek, Fissell and Roy have patent applications on this work pending.

Figures

Figure 1
Figure 1
(A) Conceptual drawing of implantable artificial kidney (IAK) in situ. (Figure modified from Kim et al., 2015 ((Kim et al., 2015), with permission from Frontiers in Bioscience.) The two candidate designs, parallel (B) and serpentine (C), are shown from two angles. Both devices have 20 channels to house nano-pore filters. The channels are arranged in parallel for the parallel device and in series for the serpentine device. (D) Photograph of experimental set up for in vivo determination of pressure boundary conditions. Arrows indicate flow direction.
Figure 2
Figure 2
Graphs of in vivo-measured pressures (mmHg) and numerically simulated flow (ml/min) over time for the parallel device (top panel) and serpentine device (bottom panel).
Figure 3
Figure 3
Low wall shear stress (WSS< 1 Pa) regions and design feature improvements at steady flow. Top row demonstrates (A) initial and (B) revised parallel plate manifold features. Bottom row demonstrates (C) initial and (D) revised serpentine turn features. The span of low WSS regions was reduced using CFD to guide design iterations.
Figure 4
Figure 4
Histograms illustrating the distribution of strain rates for the parallel design at minimum (A) and maximum (B) flow rates and for the serpentine design at minimum (C) and maximum (D) flow rates.
Figure 5
Figure 5
Velocity distributions are shown for the parallel device at maximum (1750 ml/min; A) and minimum (1170 ml/min; B) flow rates and for the serpentine device at maximum (1100 ml/min; C) and minimum (640 ml/min; D) flow rates.
Figure 6
Figure 6
Platelet activation limit summarized by Hellums et al. (Hellums et al., 1987) and values of average shear stress and residence times for the parallel (square) and serpentine (triangle) devices.
Figure 7
Figure 7
Top panel shows the linear, single-pass probability density functions (PDFs) of stress accumulation (Pa-s) for the parallel device (orange line) and serpentine device (blue line). Bottom panel shows details on the “tails” at the higher range (20–200 Pa-s) of stress accumulation.
Figure 8
Figure 8
The power law probability density functions (PDFs) for normalized lifetime stress accumulation using a power law model for the parallel (orange line) and serpentine (blue line) devices. The vertical line at a normalized stress accumulation of 1 indicates the activation limit described in Hellums, et al. (Hellums et al., 1987).
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