Templating of cell spreading and proliferation is described that yields confluent layers of cells aligned across an entire two-dimensional surface. The template is a reactive, two-component interface that is synthesized in three steps in nanometer thick, micron-scaled patterns on silicon and on several biomaterial polymers. In this method, a volatile zirconium alkoxide complex is first deposited at reduced pressure onto a surface pattern that is prepared by photolithography; the substrate is then heated to thermolyze the organic ligands to form surface-bound zirconium oxide patterns. The thickness of this oxide layer ranges from 10 to 70 nanometers, which is controlled by alkoxide complex deposition time. The oxide layer is treated with 1,4-butanediphosphonic acid to give a monolayer pattern whose composition and spatial conformity to the photolithographic mask are determined spectroscopically. NIH 3T3 fibroblasts and human bone marrow-derived mesenchymal stem cells attach and spread in alignment with the pattern without constraint by physical means or by arrays of cytophilic and cytophobic molecules. Cell alignment with the pattern is maintained as cells grow to form a confluent monolayer across the entire substrate surface.
A two-step synthesis
is described for activating the surface of a fully hydrated hydrogel
that is of interest as a possible scaffold for neural regeneration
devices. The first step exploits the water content of the hydrogel
and the hydrophobicity of the reaction solvent to create a thin oxide
layer on the hydrogel surface using a common titanium or zirconium
alkoxide. This layer serves as a reactive interface that enables rapid
transformation of the hydrophilic, cell-nonadhesive hydrogel into
either a highly hydrophobic surface by reaction with an alkylphosphonic
acid, or into a cell-adhesive one using a (α,ω-diphosphono)alkane.
Physically imprinting a mask (“debossing”) into the
hydrogel, followed by a two-step surface modification with a phosphonate,
allows for patterning its surface to create spatially defined, cell-adhesive
regions.
Polymeric sheets
were perforated by laser ablation and were uncompromised
by a debris field when first treated with a thin layer of photoresist.
Polymer sheets perforated with holes comprising 5, 10, and 20% of
the nominal surface area were then patterned in stripes by photolithography,
which was followed by synthesis in exposed regions of a cell-attractive
zirconium oxide-1,4-butanediphosphonic acid interface. Microscopic
and scanning electron microscopy analyses following removal of unexposed
photoresist show well-aligned stripes for all levels of these perforations.
NIH 3T3 fibroblasts plated on each of these perforated surfaces attached
to the interface and spread in alignment with pattern fidelity in
every case that is as high as that measured on a nonperforated, patterned
substrate.
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