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Synthetic Ice
Modulators (SIMs)*
High
cooling rates are required to suppress crystallization in cryopreservation by
vitrification. Due to the underlying principles of heat transfer, there is a
size limit above which vitrification becomes impractical at the center of the
specimen. The high cooling rates required for vitrification may give rise to thermo-mechanical
stress, driven by the physical property of thermal expansion. Due to the
underlying principles of solid mechanics, the thermo-mechanical stress also
increases with the specimen size for a given cooling rate. When the stress
exceeds the strength of the material, structural damage follows with fracture
formation as its most dramatic outcome. Synthetic
ice modulators can help alleviate cooling rate and size limitations in
vitrification. When the cryoprotective agent (CPA) is mixed with SIMs, the
cooling rates necessary to control ice formation decrease and, thereby, the
resulting stresses.
In broad terms, SIMs are compounds that
influence the formation and growth of ice nuclei and crystals by various
purported mechanisms [PubMed].
This general classification embraces several categories of molecules that
have been shown to modulate ice formation and growth. For example, molecules
such as 1,3-cyclohexanediol (1,3-CHD) that specifically attenuates the growth
of ice crystals by virtue of its chemical structure have been referred to as
synthetic ice blockers (SIBs).
Other SIMS such as 2,3-butanediol (2,3-BD) and polyethylene glycol
(PEG400) facilitate the stability of the amorphous state by virtue of their
interactions with water. As such, ice modulators make useful stabilizing
supplements to vitrification solutions to enhance their amorphous stability
and help reduce both the concentrations of other cryoprotectant solutes
necessary and the likelihood of ice formation. See also movies
on blood vessels vitrification using SIMs. *
Terminology: While the synthetic ice blocker (SIB) is a more common
term in the literature, the synthetic ice modulator (SIM) has been termed by
our research group. To a large extent, the SIM classification is a practical
one—it is derived from the outcome of adding the corresponding
compounds into the cryopreservation cocktail, rather than attributing that
outcome to a unique physical mechanism. Selected
publications: •
Ehrlich,
L.E., Gao, Z., Bischof, J.C., Rabin, Y. (2020): Thermal conductivity of
cryoprotective agents loaded with nanoparticles, with application to recovery
of preserved tissues and organs from cryogenic storage.
https://doi.org/10.1371/journal.pone.0238941 PlosONE, PubMed •
Wowk, B.G.,
Fahy, G.M, Ahmedyar, S., Taylor, M.J., Rabin, Y.
(2018): Vitrification tendency and stability of DP6 vitrification solutions
for complex tissue cryopreservation, Cryobiology, 82:70-77, PubMed,
HHS Public Access,
ScienceDirect
•
Solanki,
P.K., Rabin, Y. (2018): Analysis of polarized-light effects in
glass-promoting solutions with applications to cryopreservation and organ
banking, 13(6): e0199155, PubMed, HHS
Public Access, Plos ONE •
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 •
Ehrlich,
L.E., Malen, J.A., Fahy, G.M, Wowk, B.G., Rabin, Y. (2017): Thermal analyses of
a human kidney and a rabbit kidney during cryopreservation by vitrification,
ASME Journal of Biomechanical Engineering, doi:10.1115/1.4037406 PubMed, HHS Public
Access, ASME
Digital Collection, BTTL
Depository •
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., 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 •
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 Acknowledgements:
This
research has been supported, in part, by: • National Heart Lung and Blood Institute (NHLBI) Grant
R01HL127618 • US
Army – Defense Health Program Contract H151-013-0162 • 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 |
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