Cryopreservation mechanisms in blood vessels using ice modulators

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 DESCRIPTION: The importance of cryopreservation for tissue banking and transplant medicine is indisputable, being the only practical alternative for long-term storage of high quality biomaterials. While successful techniques for cryopreservation have been developed over the past five decades, they are generally related to small specimens, in the scale-range of cell clusters to small-organized tissues (µm to mm range), with stem cells and corneas as examples. Cryopreservation of larger-size specimens (cm and above) has been accomplished only in cases where the mechanical functionality has a higher priority need than the recovery of biological functionality, with heart valves as an example. Nevertheless, the science and technology of cryopreservation have dramatically advanced in recent years, and the successful application of cryopreservation to large tissue structures and organs is closer than ever before. Cryopreservation success revolves essentially around controlling ice formation-the cornerstone of cryoinjury. The current research focuses on suppressing crystallization by the presence of highly viscous materials, known as cryoprotective agents (CPAs), in a process known as verification (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. In fact, these effects represent competing needs important for selecting CPAs and their concentrations, and represent a significant barrier to the development of cryopreservation technology. The current project seeks to alleviate this coupling by combining synthetic ice-modulators (SIMs) with the CPA cocktail, which influence the formation and growth of ice crystals. This project represents a holistic approach to the study of cryopreservation. The research team brings together expertise from the disparate fields of biology, chemistry, physics, thermal engineering, and solid mechanics, while combining modeling tools with experimental investigation. Substantial data has been presented recently on cryopreservation by vitrification with a selected set of SIMs, as they pertain to small blood vessel segments and rings. The current project targets scale-up cryopreservation of blood vessels as key building blocks for cryopreservation applications in bulky tissues, organs, and engineered tissue constructs. The relating technology is translational and the applied scientific and engineering tools are essentially the same, which signifies the potential impact of this study. Specific aims for this project are: (i) to measure key physical properties of the biomaterials, (ii) to perform cryomacroscopic investigation of relevant physical events such as crystallization and fracturing, (iii) to investigate the mechanical behavior of the materials, (iv) to evaluate viability and functional recovery of the specimen post cryopreservation, and (v) to model cryopreservation by vitrification while integrating the knowledge developed in the other specific aims. This modeling is deemed an essential tool for future technology developments and process optimization.