EXPERIMENTAL AND COMPUTATIONAL STRATEGIES FOR ENHANCING MASS TRANSPORT AND CRYOPRESERVATION OF BIOLOGICAL TISSUES

1 online resource (126 pages) : PDF

2012

University of North Carolina at Charlotte

A bioreactor is a large-scale engineered in vitro device that maintains a 3D arrangement of functioning cells for use in various bioengineering applications. The current work is focused on heat and mass transfer issues related to the bioreactor's performance and applications. Firstly, for bioreactors to achieve high functional output, the cells within its 3D tissues constructs must have adequate supplies of nutrients and gases (O2, CO2 etc). Among these, O2 transport has been a major challenge since regions of hyperoxia and hypoxia can develop. Hence, in the first phase of this work, an O2 transport based computational model is proposed to help simulate the distribution of O2 through the volume of the 3D tissue constructs under various operational conditions. The advantage of such a predictive model is that it can supply preliminary data, helpful for optimizing O2 delivery to the cells. Secondly, the off the shelf availability of the cells and tissues utilized in the bioreactors is maintained mainly through cryopreservation techniques. In the case of large tissues, cryopreservation success is governed by the cryopreservation protocol used. Therefore, in the second phase of this work, a user friendly computational tool able to predict and compare the effectiveness of various cryopreservation protocols is developed. The computational tool's predictions are briefly validated against experimental results to verify its predictive accuracy. The package is designed to offer a cost effective solution for designing protocol's for cryopreserving 3D tissues and tissue equivalent. Thirdly, with specific relevance to the cryopreservation of liver cells and tissues, it was hypothesized that increased aquaporin (AQP) (integral membrane proteins which aid water transport) expressions on the cellular membrane would improve cellular water transport and thereby improve the cryopreservation efficiency. Experimental results showed increased cell viability following cryopreservation of liver tissues equivalents treated for translocation of AQPs to the cellular membrane, thus confirming the hypothesis to be true. Overall, the computational and experimental strategies proposed in the current work would help enhance heat and mass transport to biological tissues, resulting in potential improvement in the performance of bioreactors and other large scale tissue replacement systems.

doctoral dissertations

Mechanical engineering
Biomedical engineering

Ph.D.

Aquaporins
Computational Model
Cryopreservation
Hepatocytes
Oxygen Transport

Mechanical Engineering

Coger, Robin
Lee, Charles

Schrum, Laura
El-Ghannam, Ahmed
Du, Xiuxia

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2012.

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KarthikKumar_uncc_0694D_10401

http://hdl.handle.net/20.500.13093/etd:1554