Cryopreservation technologies represent a potential long term and minimally damaging method to preserve both native and engineered tissues. Conventional cryopreservation of allogeneic veins involving freezing is currently being used clinically, but in vivo studies using these grafts in both animal models and patients have demonstrated poor long-term patency rates. An alternative approach to cryopreservation involving vitrification that avoids the hazards of ice formation leads to a markedly improved vascular product in terms of both structure and function. Vitrification (vitreous means glassy in Latin) is essentially the solidification of a supercooled liquid by adjusting the chemical composition and cooling rate such that the crystal phase is avoided. This new preservation technology is now being scaled up for application to clinical specimens and ultimately engineered blood vessels. Nevertheless, additional hazards related to thermo-mechanical stresses in bulk vitrified specimens must be avoided for successful cryopreservation of tissues. Our long term goal is to reduce the destructive mechanical stresses induced during cryopreservation of tissues in general, and of blood vessels in particular. The purpose of this research is to develop engineering tools and to characterize the level of thermo-mechanical stresses in bulky cryopreserved tissues and thereby devise techniques to reduce, or circumvent, these stresses and develop improved methods of long term storage of both native and engineered vascular grafts.
The specific aims are to undertake a systematic study of thermo-mechanical stresses in cryopreserved blood vessels by measuring thermal expansion and stress-strain relationships. The measured parameters with appropriate mathematical modeling and computers simulations, will provide guidelines for minimizing the thermo-mechanical stresses and reduce the potential of fracture formation during cryopreservation. Although the experimental work in this study is targeted to blood vessels, the results of this study could be expanded and become useful for a wide variety of cryopreserved natural tissues and engineered constructs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL069944-04
Application #
7119997
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Lundberg, Martha
Project Start
2003-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2006
Total Cost
$313,233
Indirect Cost
Name
Carnegie-Mellon University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Noday, Daniel A; Steif, Paul S; Rabin, Yoed (2009) Viscosity of cryoprotective agents near glass transition: a new device, technique, and data on DMSO, DP6, and VS55. Exp Mech 49:663-672
Steif, Paul S; Noday, Daniel A; Rabin, Yoed (2009) Can thermal expansion differences between cryopreserved tissue and cryoprotective agents alone cause cracking? Cryo Letters 30:414-21
Steif, Paul S; Palastro, Matthew C; Rabin, Yoed (2008) Continuum mechanics analysis of fracture progression in the vitrified cryoprotective agent DP6. J Biomech Eng 130:021006
Steif, Paul S; Palastro, Matthew C; Rabin, Yoed (2007) Analysis of the effect of partial vitrification on stress development in cryopreserved blood vessels. Med Eng Phys 29:661-70
Jimenez Rios, Jorge L; Steif, Paul S; Rabin, Yoed (2007) Stress-strain measurements and viscoelastic response of blood vessels cryopreserved by vitrification. Ann Biomed Eng 35:2077-86
Jimenez Rios, Jorge L; Rabin, Yoed (2007) A New Device for Mechanical Testing of Blood Vessels at Cryogenic Temperatures. Exp Mech 47:1741-2765
Steif, Paul S; Palastro, Matthew C; Rabin, Yoed (2007) The Effect of Temperature Gradients on Stress Development During Cryopreservation via Vitrification. Cell Preserv Technol 5:104-115
Baicu, S; Taylor, M J; Chen, Z et al. (2006) Vitrification of Carotid Artery Segments: An Integrated Study of Thermophysical Events and Functional Recovery Toward Scale-Up for Clinical Applications. Cell Preserv Technol 4:236-244
Rios, Jorge L Jimenez; Rabin, Yoed (2006) Thermal expansion of blood vessels in low cryogenic temperatures, Part II: Vitrification with VS55, DP6, and 7.05 M DMSO. Cryobiology 52:284-94
Jimenez Rios, Jorge L; Rabin, Yoed (2006) Thermal expansion of blood vessels in low cryogenic temperatures Part I: A new experimental device. Cryobiology 52:269-83

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