Microfabrication and biomedical applications of micropatterning
Date Issued
2012
Date
2012
Author(s)
Chien, Hsiu-Wen
Abstract
Cellular patterning on biomaterial surfaces is important in fundamental studies of cell–cell and cell–substrate interactions, and in biomedical applications such as tissue engineering, cell-based biosensors, and diagnostic devices. The objective of this study was to design selective adhesion of cells to a substrate with a region of adhesive surface and nonadhesive surface representing a pattern. The control cell spatial adhesion and the development of cellular pattering by incorporated microfabrications and surface modifications were applied to various biomedical fields.
The first part, we combined the layer-by-layer polyelectrolyte multilayer deposition and photolithography to create an easy and versatile technique for cell patterning. Poly(acrylic acid) (PAA) conjugated with 4-azidoaniline was interwoven in PAA/polyacrylamide (PAM) multilayer films. After UV irradiation through a photo mask, the UV-exposed areas were crosslinked and the unexposed areas were rinsed away by alkaline water, resulting in micropatterns. Cell patterns were formed when the cell adhesion was limited to the base substrate, but not on the multilayer films. The stability of cell patterns could be modulated by simply modification of the surface chemistry of base substrate and PEM films with conjugation of bioactive macromolecules. Cell co-culture systems can be also achieved by this technique.
The second part, a simple technique was developed to fabricate tuneable micropatterned substrates based on mussel-inspired surface modification. Polydopamine (PDA) was developed on polydimethylsiloxane (PDMS) stamps and was easily imprinted to several substrates such as glass, silicon, gold, polystyrene and polyethylene glycol via microcontact printing. The imprinted PDA retained its unique reactivity and could modulate the chemical properties of micropatterns via secondary reactions, which was illustrated in this study. PDA patterns imprinted onto a cytophobic and nonfouling substrates were used to form patterns of cells or proteins. PDA imprints reacted with nucleophilic amines or thiols to conjugate molecules such as polyethylene glycol for creating non-fouling area. Gold nanoparticles were immobilized onto PDA-stamped area. The reductive ability of PDA transformed silver ions to elemental metals as an electroless process of metallization. This facile and economic technique provides a powerful tool for development of a functional patterned substrate for various applications.
Next, we modified a technique combining mussel-inspired surface chemistry and micro-contact printing (uCP) to modulate surface chemistry for cell patterning. The cell affinity of PDA was modulated by co-deposition with several poly(ethylene imine) (PEI)-based copolymers such as PEI, PEI-g-PEG (poly(ethylene glycol)) and PEI-g-galactose. The imprints of PDA/PEI-g-PEG benefit the formation of cell patterns on cell-favorable substrates. Neuronal PC12 cells were patterned via imprinting of PDA/PEI, while HepG2/C3A cells were arranged on the imprint of PDA/PEI-g-galactose. Finally, co-culture of HepG2/C3A cells and L929 fibroblasts was accomplished by our micro-patterning approach. This study demonstrated this facile and economic technique provides a powerful tool for development of functional patterned substrates for cell patterning.
Subjects
micropatterning
surface chemistry
cell-substrate interaction
cell-cell interaction
co-culture
Type
thesis
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