Synthesis and microfabrication of elastomeric biomaterials for advanced tissue engineering scaffolds

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2008.Vita.Includes bibliographical references (leaves 241-251).The subject of this thesis lies at the interface of microfabrication technology and advanced biomaterials synthesis and processing for use in designing and fabricating novel tissue engineered constructs. The unifying theme is to use micron and sub-micron fabrication strategies to form advanced tissue engineering scaffolds which are able to precisely control the microenvironment of cells. These efforts are organized into two thrusts; (1) materials synthesis and process development for microfluidic scaffold fabrication and (2) micro- and nanofabricated synthetic substratum for controlling cell function. In the first thrust, materials-specific processes for the fabrication of poly(glycerol-co-sebacate), a synthetic elastomeric biodegradable polyester, into three-dimensional, hepatocyte-seeded microfluidic constructs is discussed. Material advantages of natural proteins motivated the fabrication of next-generation microfluidic scaffolds using silk fibroin from the Bombyx mori as a bulk material. The need to combine the advantages of both natural proteins and synthetic polyesters motivated the synthesis and characterization of a new class of biodegradable elastomers termed poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate) (APS). APS polymers are tunable and possess the advantages of both natural and synthetic polymers. APS polymers induce a favorable biomaterial-tissue response including reduced fibrous capsule formation and macrophage recruitment compared to PLGA. In vivo degradation half lives could be controlled to between approximately 6 and 100 wks by adjusting polymer composition and processing. The second thrust focuses on the interaction with cells and synthetically fabricated nanotopographic substrates for potential in vascularized tissue engineering applications.(cont.) The contact guidance response of human embryonic stem cells to poly(dimethylsiloxane) (PDMS) substrates with 600 nm ridge-groove geometry and 600 ± 150 nm feature height was characterized. This motivated the study of endothelial progenitor cell function and morphology on nanofabricated PDMS substrates. Endothelial progenitor cells (EPCs) were found to exhibit increased doubling time from 16.2 ± 0.8 to 20.9 ± 1.9 h for cells grown on flat and nanotopographic substrates, respectively. EPCs cultured on nanotopographic substrates had a faster velocity and enhanced directed migration. The average velocity of EPCs on nanotopographic and flat substrates was 0.80 ± 0.45 and 0.54 ± 0.27 pm-min-1, respectively, while the effective displacement due to migration was 23.6 + 12.1 and 15.6 ± 10.1 Pm. Lastly, an in vitro capillary tube formation assay induced the formation of larger, more organized vascular structures in EPCs cultured on nanotopographic (411 ± 209 pm) versus flat substrates (140 + 35.6 [mu]m). This work has validated the potential impact of microfabricated scaffolds in tissue engineering by modulating cell function and controlling microenvironmental parameters.by Christopher John Bettinger.Ph.D