A microfabricated 3D tissue engineered "Liver on a Chip" : information content assays for in vitro drug metabolism studies

(cont.) approaches to improving hepatocyte function in culture have been described, not all of the important functions--specifically the biotransformation functions of the liver--can as yet be replicated at desired in ivo levels, especially in culture formats amenable to routine use in drug development. The in vivo microenvironment of hepatocytes in the liver capillary bed includes signaling mechanisms mediated by cell-cell and cell-matrix interactions, soluble factors, and mechanical forces. This thesis focuses on the design, fabrication, modeling and characterization of a microfabricated bioreactor system that attempts to mimic the in vivo microenvironment by allowing for the three dimensional morphogenesis of liver tissue under continuous perfusion conditions. A key feature of the bioreactor that was designed is the distribution of cells into many tiny ([approximately]0.001 cm³) tissue units that are uniformly perfused with culture medium. The total mass of tissue in the system is readily adjusted for applications requiring only a few thousand cells to those requiring over a million cells by keeping the microenvironment the same and scaling the total number of tissue units in the reactor. Using a computational fluid dynamic model in ADINA® and a species conservation mass transfer model in FEMLAB®, the design of the bioreactor and the fluidic circuit was optimized to mimic physiological shear stress rates ...

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Sivaraman, Anand, 1977-

Advisor dc:contributor.advisor

• Linda G. Griffith.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/28661

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/28661