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Thermo-Mechanical Stress in Cryopreservation

 

Cryopreservation success revolves around controlling ice formation—the cornerstone of cryoinjury. The current line of research focuses on suppressing crystallization in the presence of highly viscous materials, known as cryoprotective agents (CPAs), in a process known as vitrification (vitreous in Latin means glassy). While vitrification is a well-understood phenomenon, its application to biological systems comes with the potentially harmful effects of toxicity of the CPA and structural damage due to thermo-mechanical stresses.

 

The objective of this line of research is to reduce thermo-mechanical stress in large-size specimens and thereby prevent structural damage. This line of research integrates: (i) visualization of physical events associated with cryopreservation using cryomacroscopy, (ii) measurements of physical properties in cryogenic temperatures, (iii) modeling for thermo-mechanical stress in vitrification, and (iv) simulations of thermo-mechanical stress formation in cryopreservation protocols.

 

While current research efforts target the blood vessel as an investigation model, the observed phenomena and analyses are applicable to a wide variety of biomaterials and cryopreservation conditions. For example, a cryopreserved blood vessel where both crystallization and fractures are avoided—observed with a cryomacroscope [PubMed]:

 

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Recent research efforts at the BTTL focus on further suppressing ice growth by means of synthetic ice modulators (SIMs), and on decreasing thermo-mechanical stress during the rewarming phase of the cryogenic protocol by means of volumetric heating using magnetic nanoparticles in an AC magnetic field.

 

Selected publications:

       Solanki, P.K., Rabin, Y. (2017): Thermal expansion of the cryoprotective agent cocktail DP6 in combination with various synthetic ice modulators, ASME Bioengineering and Biotransport Conference, Tucson, AZ, USA (June 21-24) BTTL Depository

       Solanki, P.K., Bischof, J.C., Rabin, Y. (2017): Thermo-mechanical stress analysis of cryopreservation in cryobags and the potential benefit of nanowarming, Cryobiology, 76:129-139 PubMed, HHS Public Access, ScienceDirect

       Feig, J.S.G., Solanki, P.K., Eisenberg, D.P., Rabin, Y. (2016): Polarized light scanning cryomacroscopy, Part II: thermal modeling and analysis of experimental observations, Cryobiology, 73(2):272-281 PubMed, HHS Public Access, ScienceDirect

       Feig, J.S.G., Eisenberg, D.P., Rabin, Y. (2016): Polarized light scanning cryomacroscopy, Part I: Experimental apparatus and observations of vitrification, Crystallization, and Photoelasticity Effects, Cryobiology, 73(2):261-71 PubMed, HHS Public Access, ScienceDirect

       Eisenberg, D.P., Bischof, J.C., Rabin, Y. (2015): Thermo-mechanical stress in cryopreservation via vitrification with nanoparticle heating as a stress-moderating effect, ASME Journal of Biomechanical Engineering, 138(1), doi: 10.1115/1.4032053 PubMed, ASME Digital Collection

       Eisenberg, D.P., Rabin, Y. (2015): Stress-strain measurements in vitrified arteries permeated with synthetic ice modulators, ASME Journal of Biomechanical Engineering, 137(8):0810071-0810077, doi:10.1115/1.4030294. PubMed, HHS Public Access, ASME Digital Collection

       Eisenberg, D.P., Steif, P.S., Rabin, Y. (2014): On the effects of thermal history on the development and relaxation of thermo-mechanical stress in cryopreservation, Cryogenics, 64:86–94 PubMed, HHS Public Access

       Feig, J.S.G., Rabin, Y. (2014):  The scanning cryomacroscope with applications to cryopreservation – a device prototype, Cryogenics, 62:118–128 HHS Public Access, ScienceDirect

       Eisenberg, D.P., Taylor, M.J., Jorge L. Jimenez-Rios, Rabin, Y. (2014): Thermal expansion of vitrified blood vessels permeated with DP6 and synthetic ice modulators, Cryobiology, 68(3):318-26 PubMed, HHS Public Access, ScienceDirect

       Rabin, Y., Taylor, M.J., Feig, J.S.G., Baicu, S., Chen, Z. (2013): A new cryomacroscope device (Type III) for visualization of physical events in cryopreservation with applications to vitrification and synthetic ice modulators, Cryobiology 67(3):264-73 PubMed, HHS Public Access, ScienceDirect

       Rabin, Y., Feig, J.S.G., Williams, A.C., Lin, C.C., Thaokar, C. (2012): Cryomacroscopy in 3D: a device prototype for the study of cryopreservation. ASME 2012 Summer Bioengineering Conference - SBC 2012, Fajardo, Puerto Rico, USA (June 20-23) ASME Digital Collection, BTTL Depository

       Eisenberg, D.P., Taylor, M.J., Rabin, Y. (2012): Thermal expansion of DP6 combined with synthetic ice blockers in presence and absence of biological tissues. Cryobiology, 65(2):117-125 PubMed, HHS Public Access, ScienceDirect

       Eisenberg, D.P., Rabin, Y. (2011): The effect of synthetic ice blockers on thermal expansion of the cryoprotective cocktail DP6. ASME 2011 Summer Bioengineering Conference - SBC 2011, Farmington, PA, USA (June 22-25) ASME Digital Collection

       Noday, D.A., Steif, P.S., Rabin, Y. (2009): Viscosity of cryoprotective agents near glass transition: a new device, technique, and data on DMSO, DP6, and VS55. Journal of Experimental Mechanics, 49(5):663-672 PubMed, HHS Public Access, BTTL Depository

       Steif, P.S., Noday, D.A., Rabin, Y. (2009): Can thermal expansion differences between cryopreserved tissue and cryoprotective agents alone cause cracking? CryoLetters 30(6):414-421 PubMed, HHS Public Access, BTTL Depository

       Baicu, S., Taylor, M.J., Chen, Z., Rabin, Y. (2008): Cryopreservation of carotid artery segments via vitrification subject to marginal thermal conditions: Correlation of freezing visualization with functional recovery. Cryobiology, 57(1):1-8 PubMed, HHS Public Access, ScienceDirect, BTTL Depository

       Steif, P.S., Palastro, M.C, Rabin, Y. (2008): Continuum mechanics analysis of fracture progression in the vitrified cryoprotective agent DP6. ASME Biomechanical Engineering, 130(2):021006 PubMed, HHS Public Access, ASME Digital Collection

       Jimenez Rios, J.L., and Rabin, Y. (2007): A new device for mechanical testing of blood vessels at cryogenic temperatures. Journal of Experimental Mechanics 47:337–346 (Special issue on: Mechanics of Organic, Implant, and Bioinspired Materials) PubMed, HHS Public Access, BTTL Depository

       Steif, P.S., Palastro, M.C, Rabin, Y. (2007): The effect of temperature gradients on stress development during cryopreservation via vitrification. Cell Preservation Technology 5(2):104-115 PubMed, HHS Public Access, BTTL Depository

       Jimenez Rios, J.L., Paul S. Steif, and Rabin, Y. (2007): Stress-strain measurements and viscoelastic response of blood vessels cryopreserved by vitrification. Annals of Biomedical Engineering 35(12):2077-2086 PubMed, HHS Public Access, Springer Link, BTTL Depository

       Jimenez Rios, J.L., Rabin, Y. (2006): Thermal expansion of blood vessels in low cryogenic temperatures, Part I: A new experimental device. Cryobiology, 52(2):269-283 PubMed, HHS Public Access, ScienceDirect, BTTL Depository

       Jimenez Rios, J.L., and Rabin, Y. (2006): Thermal expansion of blood vessels in low cryogenic temperatures, Part II: Measurements of blood vessels vitrified with VS55, DP6, and 7.05M DMSO. Cryobiology, 52(2):284-294 PubMed, HHS Public Access, ScienceDirect, BTTL Depository

       Rabin, Y., Steif, P.S., Hess, K.C., Jimenez-Rios, J.L., Palastro, M.C. (2006): Fracture formation in vitrified thin films of cryoprotectants. Cryobiology, 53:75-95 PubMed, HHS Public Access, ScienceDirect, BTTL Depository

       Baicu, S., Taylor, M.J., Chen, Z., Rabin, Y. (2006): Vitrification of carotid artery segments: An integrated study of thermophysical events and functional recovery towards scale-up for clinical applications. Cell Preservation Technology, 4(4):236-244 PubMed, HHS Public Access, BTTL Depository

       Steif, P.S., Palastro, M.C, Rabin, Y. (2006): Analysis of the effect of partial vitrification on stress development in cryopreserved blood vessels. Medical Engineering & Physics, 29(6):661-670 PubMed, HHS Public Access, ScienceDirect, BTTL Depository

       Rabin, Y., Steif, P.S. (2006): Solid mechanics aspect of cryobiology, In: Advances in Biopreservation (Baust, J.G., and Baust J.M., Eds.), CRC Taylor & Francis, Chap. 13, pp. 359-382

       Rabin, Y., Plitz, J. (2005): Thermal expansion of blood vessels and muscle specimens permeated with DMSO, DP6, and VS55 in cryogenic temperatures. Annals of Biomedical Engineering, 33(9):1213 – 1228 PubMed, Springer Link, BTTL Depository

       Rabin, Y., Taylor, M.J., Walsh, J.R., Baicu, S., Steif, P.S. (2005): Cryomacroscopy of vitrification, Part I: A prototype and experimental observations on the cocktails VS55 and DP6. Cell Preservation Technology, 3(3):169-183 PubMed, HHS Public Access, BTTL Depository

       Steif, P.S., Palastro, M., Wen, C.R., Baicu, S., Taylor, M.J., Rabin, Y. (2005): Cryomacroscopy of vitrification, Part II: Experimental observations and analysis of fracture formation in vitrified VS55 and DP6. Cell Preservation Technology, 3(3):184-200 PubMed, HHS Public Access, BTTL Depository

       Rabin, Y., Steif, P.S. (2005): Letter-to-the-Editor: Analysis of thermo-mechanical stress in cryopreservation. CryoLetters, 26(6):409-411 PubMed, HHS Public Access, BTTL Depository

       Plitz, J., Rabin, Y., Walsh, J., (2004): The effect of thermal expansion of ingredients on the cocktails VS55 and DP6. Cell Preservation Technology, 2(3):215-226 Mary Ann Liebert, BTTL Depository

       Rabin, Y., Bell, E. (2003): Thermal expansion measurements of cryoprotective agents. Part I: A new experimental apparatus. Cryobiology, 46(3):254-263 PubMed, ScienceDirect, BTTL Depository

       Rabin, Y., Bell, E., (2003): Thermal expansion measurements of cryoprotective agents. Part II: Measurements of DP6 and VS55, and comparison with DMSO. Cryobiology, 46(3):264-270 PubMed, ScienceDirect, BTTL Depository

       Rabin, Y., Steif, P.S. (2000): Thermal stress modeling in cryosurgery. International Journal of Solids and Structures 37:2363-2375 ScienceDirect, BTTL Depository

       Rabin, Y., Rittel, D. (2000): Infrared temperature sensing of mechanically loaded specimens: thermal analysis. Experimental Mechanics, 40(2):197-202 Springer Link, BTTL Depository

       Dennis, B.H., Dulikravich, G.S., Rabin, Y. (2000): Optimization of organ freezing protocols with specified allowable thermal stress levels. International Mechanical Engineering Congress and Exposition 2000, Orlando, FL, November 5-10, HTD-Vol. 368/BED-Vol. 47, pp. 33-48 BTTL Depository

       Rabin, Y., Steif, P.S. (1999): Thermal stress modeling of freezing biological tissues. In: Advances in Heat and Mass Transfer in Biotechnology, International Mechanical Engineering Congress and Exposition 1999, Nashville, Tennessee. HTD-Vol. 363, BED-Vol. 44, pp. 183-188 BTTL Depository

       Rabin, Y., Taylor, M.J., Wolmark, N. (1998): Thermal expansion measurements of frozen biological tissues at cryogenic temperatures. ASME Journal of Biomechanical Engineering, 120(2):259-266 PubMed, ASME Digital Collection, BTTL Depository

       Rabin, Y., Steif, P.S. (1998): Thermal stresses in a freezing sphere and its application to cryobiology. ASME Journal of Applied Mechanics, 65(2):328-333 ASME Digital Collection, BTTL Depository

       Rabin, Y., Olson, P., Taylor, M.J., Steif, P.S., Julian, T.B., Wolmark, N. (1997): Gross damage accumulation in frozen rabbit liver due to mechanical stress at cryogenic temperatures. Cryobiology, 34:394-405 PubMed, ScienceDirect, BTTL Depository

       Rabin, Y., Steif, P.S. (1996): Analysis of thermal stresses around a cryosurgical probe. Cryobiology, 33:276-290 PubMed, ScienceDirect, BTTL Depository

       Rabin, Y., Steif, P.S., Taylor, M.J., Julian, T.B., Wolmark, N. (1996): An experimental study of the mechanical response of frozen biological tissues at cryogenic temperatures. Cryobiology, 33:472-482 PubMed, ScienceDirect, BTTL Depository

 

Acknowledgements:

This research has been supported, in part, by the

       National Heart Lung and Blood Institute (NHLBI) Grant R01HL069944

       National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant R21EB011751

       National Center for Research Resources (NCRR) Grant R21RR026210

       National Institute of General Medical Sciences (NIGMS) Grant R21GM103407

       National Heart Lung and Blood Institute (NHLBI) Grant R01HL127618

        US Army – Defense Health Program Contract H151-013-0162

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