Using Chemical Patterning to Spatially Control Cell Growth: A Versatile Technology for Improving Tissue Engineering Devices

Abstract

A method for spatially controlling cell proliferation and extracellular matrix (ECM) synthesis on three biocompatible polymer substrates has been developed, with the aim of extending this procedure to three-dimensional tubes that are biomedically relevant. Flat polyethylene terapthtalate (PET) was patterned with stripes of a cell-adhesive zirconium oxide (ZrO\(_{2}\))/self-assembled monophosphonate layer (SAMP) layer that induces cells to proliferate and extend in alignment with this pattern. These flat PET surfaces were then rolled into tubular structures and NIH 3T3 cells were seeded on the inside, demonstrating that cells will grow in alignment with the pattern in a tubular conformation. A shape memory polymer (SMP) with a glass transition temperature that induces it to change from a flat surface to a “half-pipe” conformation was similarly patterned. This patterning process involved a prelimary photolithography step followed by chemical vapor deposition (CVD). Cells grew in alignment and produced densely-assembled, organized extracellular matrix on this substrate. Finally, flat and tubular polycaprolactone fumarate (PCLF), a polymer substrate that has previously been shown to be best suited for use as a peripheral nerve conduit, was patterned with the same ZrO\(_{2}\)/SAMP interface using a shadow masking technique followed by CVD. Cells plated on flat PCLF surfaces grew in the direction of the chemical patterns and assembled aligned ECM. Neuron-like PC12 cells plated on top of decellularized ECM extended neurites in alignment with these patterns. These preliminary results indicate that this patterning procedure has the potential to greatly improve implantable peripheral nerve conduits.