Research Papers

Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification

[+] Author and Article Information
Lili E. Ehrlich, Jonathan A. Malen

Department of Mechanical Engineering,
Carnegie Mellon University,
Pittsburgh, PA 15213

Gregory M. Fahy, Brian G. Wowk

21st Century Medicine, Inc.,
Fontana, CA 92336

Yoed Rabin

Department of Mechanical Engineering,
Carnegie Mellon University,
Pittsburgh, PA 15213
e-mail: rabin@cmu.edu

1Corresponding author.

Manuscript received April 14, 2017; final manuscript received July 7, 2017; published online October 26, 2017. Assoc. Editor: Ram Devireddy.

J Biomech Eng 140(1), 011005 (Oct 26, 2017) (8 pages) Paper No: BIO-17-1153; doi: 10.1115/1.4037406 History: Received April 14, 2017; Revised July 07, 2017

This study focuses on thermal analysis of the problem of scaling up from the vitrification of rabbit kidneys to the vitrification of human kidneys, where vitrification is the preservation of biological material in the glassy state. The basis for this study is a successful cryopreservation protocol for a rabbit kidney model, based on using a proprietary vitrification solution known as M22. Using the finite element analysis (FEA) commercial code ANSYS, heat transfer simulations suggest that indeed the rabbit kidney unquestionably cools rapidly enough to be vitrified based on known intrarenal concentrations of M22. Scaling up 21-fold, computer simulations suggest less favorable conditions for human kidney vitrification. In this case, cooling rates below −100 °C are sometimes slower than 1 °C/min, a rate that provides a clear-cut margin of safety at all temperatures based on the stability of rabbit kidneys in past studies. Nevertheless, it is concluded in this study that vitrifying human kidneys is possible without significant ice damage, assuming that human kidneys can be perfused with M22 as effectively as rabbit kidneys. The thermal analysis suggests that cooling rates can be further increased by a careful design of the cryogenic protocol and by tailoring the container to the shape of the kidney, in contrast to the present cylindrical container. This study demonstrates the critical need for the thermal analysis of experimental cryopreservation and highlights the unmet need for measuring the thermophysical properties of cryoprotective solutions under conditions relevant to realistic thermal histories.

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Grahic Jump Location
Fig. 1

Illustrations of system analyzed in this study: (a) a kidney in a cylindrical container filled with CPA; (b) schematic view of the four subdomains of the system, each characterized by unique thermal properties; heat transfer processes and material properties of the constituents; and (c) a cross section of the system showing the FEA mesh and virtual thermal sensors

Grahic Jump Location
Fig. 2

Thermal history in the kidney model for (a) a vitrified system with CPA properties, (b) the same system at the early stage of cooling, and (c) a vitrified system but with ice properties, where So is the outer surface of the cortex, Si is the medulla–cortex interface, Tc is the temperature of the cooling chamber, and T0 is the temperature at the center of the kidney (Fig. 1(c))

Grahic Jump Location
Fig. 3

Cooling-rate history in the vitrified kidney model, where So is the outer surface of the cortex, Si is the medulla–cortex interface (Fig. 1(c)), and CCRmed is the CCR for 87.5% M22 in the medulla (1 °C/min)

Grahic Jump Location
Fig. 4

Thermal history of sensor 9 (the closest point in the medulla to center of system) for the cases of a vitrified human kidney and a vitrified rabbit kidney. The colored areas refer to the human kidney simulation, where green (left highlighted area) corresponds to the time range in which the sensor indicates temperatures below Tm and the cooling rate is above the CCR of 87.5% M22, while red (right highlighted area) corresponds to the time range in which the sensor indicates temperatures above Tg and the cooling rate is below CCR of 87.5% M22; colored areas interface at −103 °C (between the left and right highlighted areas).

Grahic Jump Location
Fig. 5

Temperature fields when the sensor 9 indicates (a) −30 °C, (b) −60 °C, (c) −90 °C, and (d) −120 °C



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