Development of Biomimetic Interfaces and Their Applications.

This dissertation details strategies for the fabrication of sophisticated biofunctional materials and their use in biomedical and biotechnological application. These unique biointerfaces were designed by integrating biological entities with synthetic polymers and extensively characterized using surface analytical tools. The first part of this dissertation focuses on the immobilization of specific moieties that render surfaces biomimetic. Synthesis of reactive polymers, poly(4-formyl-p-xylylene-co-p-xylylene) and poly(4-heptadecafluoronononyl-p-xylylene-co-p-xylylene) was accomplished via chemical vapor deposition (CVD) polymerization. These reactive polymer coatings enabled the immobilization of proteins and oligosaccharides via chemoselective carbonyl-hydrazide coupling reaction. On the other hand, an alkyne-functionalized polymer coating, poly(4-ethynyl-p-xylylene-co-p-xylylene) was synthesized for the conjugation of proteins, saccharides and cell-adhesive oligopeptides via alkyne-azide “click” reaction, in a spatioselective manner. These platforms were further used for surface-directed adhesion of human endothelial cells. Another application of reactive polymers was directed towards the fabrication of polymer coatings, which mimic endothelial cells with respect to nitric oxide generation for cardiovascular stents. Photo-reactive polymer coatings were deposited using CVD polymerization and used to incorporate Cu(II) ligated cyclen (1,4,7,10-tetraazacyclododecane) onto the surface of a stent. These catalytic sites containing copper generated NO from endogenous S-nitrosothiols present in blood, and the measured NO flux approached physiological ranges. These coatings attempt to solve the problems of restenosis and thrombosis associated with the placement of coronary artery stents. In the second part of the dissertation, a chemically-defined polymer was fabricated, which supported long-term human embryonic stem (hES) cell cultures, for the first time, in the presence of several different culture media. Polymer, poly[2-(methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide] sustained the culture of hES cells for at least 25 passages in mouse fibroblast conditioned medium, at least 15 passages in commercially-available human cell conditioned medium and at least 10 passages in defined StemPro medium. Throughout the study, hES cells expressed undifferentiated cell markers, retained a normal karyotype and remained pluripotent. Development of a standardized culture matrix for hES cells represents a significant step towards future clinical applications of hES cells. Taken together, these approaches offer novel solutions for target applications in tissue engineering, biomedical devices and microfluidics and further expand our toolbox of strategies for creating biologically-relevant surfaces.Ph.D.Chemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/64816/1/nhima_1.pd

Reaktive Polymere, die “klicken” J.L. dankt der National Science Foundation (NSF) fÜr ein Career-Stipendium (DMR-0449462) und fÜr UnterstÜtzung im Rahmen des Major Research Instrumentation Program (DMR-0420785). Wir danken Prof. Larson (University of Michigan) fÜr Zugang zum Fluoreszenzmikroskop und Prof. J. Kim (Materials Science and Engineering, University of Michigan) fÜr Zugang zum Spektrofluorometer.

No AbstractPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55227/1/3438_ftp.pd

Biocompatible Polymers: Structurally Controlled Bio-hybrid Materials Based on Unidirectional Association of Anisotropic Microparticles with Human Endothelial Cells (Adv. Mater. 48/2009)

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64541/1/4873_ftp.pd