A range of methods including soft lithography are available for patterning protein layers for cell adhesion on quasi-planar substrates. Suitably structured, these layers favor the geometrically constrained, controlled growth of cells and the development of cellular extensions on them. For this purpose, the ability to control the shape and dimension of cell-adhesive areas with high precision is crucial. For more advanced studies of cell interactions, the surface modification or functionalization of substrates with complex topographies is desirable. This paper describes a simple technique allowing to produce surface modification patterns using delicate molecules such as laminin on substrates exhibiting pronounced topographies with recessed and protruding microstructures. The technique is based on the combination of sacrificial photoresist structures with a connected parylene-C layer. This layer locally adheres to the substrate wherever the substrate needs to be protected against the surface modification. After surface modification, the parylene-C layer is peeled off. Patterns comprising arbitrary networks of modified and unmodified substrate areas can thus be realized. We demonstrate the technique with the guided growth of neuron-like PC12 cells on networks of laminin lines on substrates structured with micropillars and microwells.
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