A novel bioengineering platform using functionalized self-assembly peptides to enhance CYP3A2 activity in modified rat hepatocyte sandwich cultures

Isolated hepatocytes removed from their microenvironment soon lose their hepatospecific functions when cultured. Highly oxygen-demanding hepatocytes are commonly maintained under oxygen-deficient culture conditions, limited by culture medium thickness as well scaffold thickness. Thus, the cells are forced into anaerobic metabolic states that degenerate liver specific functions. Furthermore, cells separated from their extracellular matrix and disconnected from the synergistic interactions between other hepatic cells types further exacerbate hepatocellular function. This study aims to improve hepatospecific activity, especially CYP3A2 - a biomarker that is notoriously known to quickly lose expression in primary cultures, by creating a platform based on collagen sandwich cultures. The modified sandwich cultures are substituted with self-assembling peptide, RAD16-I, combined with integrin-binding sequence RGD or laminin receptor binding sequence YIGSR functional peptide motifs to create a cell-instructive peptide scaffold. To facilitate oxygen and nutrient diffusion and exchange, plasma modification technology is employed to control peptide layer dimension. We have successfully shown that plasma engineering can be used to optimize peptide thickness.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Wu, Jonathan (Jonathan G.)

Advisor dc:contributor.advisor

• Carlos E. Semino and Roger D. Kamm.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

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

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/39918

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39918