The Microsystems Series has as its goal the creation of an outstanding set of textbooks, references, and monographs on subjects that span the broad field of microsystems. Exceptional PhD dissertations provide a good starting point for such a series, because, unlike monographs by more senior authors, which must compete with other professional duties for attention, the dissertation becomes the sole focus of the author until it is completed. Conversion to book form is then a streamlined process, with final editing and book production completed within a few months. Thus we are able to bring important and timely material into book form at a pace which tracks this rapidly developing field. Our first four books in the series were drawn from the more physics-oriented side of the microsystems field, including such diverse subjects as computer-aided design, atomic-force microscopy, and ultrasonic motion detection. Now, with Sangeeta Bhatia's work, we enter the realm of biology. Her use of artifically structured substrates to encourage the liver cells to form orderly assemblies is a fine example of how microfabrication technology can contribute to cell biology and medicine. I am pleased to be able to add this very new and very interesting work to the Microsystems Series. Stephen D. Senturia Cambridge MA Microfabrication in Tissue Engineering and Bioartificial Organs Foreword One of the emerging applications of microsystems technology in biology and medicine is in the field of tissue engineering and artificial organs. In order to function, cells need to receive proper signals from their environment.

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Editor's Preface. Foreword. Abstract. Acknowledgements. Contents. List of Figures. Introduction. 1. Tissue Engineering. 2. What Does The Liver Do? 3. What Happens When The Liver Fails? 4. Hepatic Tissue Engineering. 5. How Can Hepatocytes Be Stabilized In Vitro? 6. How Are Cell-Cell Interactions Important In Vivo? 7. Co-Culture. 8. Previous Attempts to Control Cell-Cell Interactions. 9. Micropatterning of Cells. 10. Scope of this Study. Methodology for Fabrication, Characterization, and Analysis of Micropatterned Co-Cultures. 1. Overview. 2. Fabrication of Micropatterned Co-Cultures. 3. Surface Characterization of Substrates. 4. Functional Analysis of Micropatterned Co-Cultures. 5. Mechanistic Studies. 6. Optimization Studies. 7. Summary. Characterization: Microfabricated Substrates & Co-Cultures. 1. Overview. 2. Characterization of Cell-Free Substrates. 3. Characterization of Micropatterned Cultures. 4. Discussion. 5. Summary. Functional Analysis of Micropatterned Co-Cultures. 1. Overview. 2. Characterization of Initial Cell Distribution. 3. Biochemical Analysis of Liver-Specific Function. 4. Hepatocyte Function In Situ: Immunostaining of Intracellular Albumin. 5. Haptocyte Function In Situ: Bile Duct Excretion. 6. Discussion. 7. Summary and Implications. 7. Summary and Implications. Probing Mechanisms of Hepatocyte/Fibroblast Interactions. 1. Overview. 2. Effect of Homotypic Hepatocyte Interactions on Spatial Pattern of Immunostaining. 3. Use of Conditioned Media. 4. Physical Separation of Cell Populations. 5. Agitation of Co-Cultures. 6. Discussion. 7. Summary and Future Work. Optimization of Hepatic Function in Co-Cultures. 1. Overview. 2. Reduction of Fibroblast: Hepatocyte Ratio While Preserving Heterotypic Interface in Micropatterned Co-Cultures. 3. Reduction of Fibroblast: Hepatocyte Ratio Without Control of Heterotypic Interface in Conventional, Randomly-Distributed Co-Cultures. 4. Comparison of Micropatterned and Randomly-Distributed Co-Cultures. 5. Discussion. 6. Summary. Conclusions and Outlook. 1. Summary. 2. Future Directions. References. Glossary. Index.