TopoChip: technology for instructing cell fate and morphology via designed surface topography

Abstract

The control of biomaterial surface topography is emerging as a tool to influence cells and tissues. Due to a lack a theoretical framework of the underlying molecular mechanisms, high-throughput screening (HTS) technology is valuable to identify and study bioactive surface topographies. To identify the bioactive topographies that can be applied to medical implants and in vitro cell culture systems the TopoChip HTS platform has been developed which contains more than 2000 unique randomly generated surface topography designs. In this thesis we used the state of the art TopoChip HTS platform to investigate bioactive topographies on materials which are similar to the intended (biomedical) application. As a first aim of the thesis, we identified and studied micro-topographies for the improvement of several different applications: an orthopedic bone implant, a membrane for a bio-artificial kidney device and tissue culture plastic ware. For example, in the case of the orthopedic bone implant application, we improved the bone bonding by screening the TopoChip for those topographies that induced osteogenic differentiation of bone marrow-derived mesenchymal stem cells. The cell shape features, surface design parameters, and osteogenic marker for protein expression were strongly correlated, and predictive value of the screen was high, as topographies with the highest osteogenic potential strongly enhanced bone bonding in a rabbit femur model. These findings support the hypothesis that the morphology and differentiation of stem cells follows design rules of the surface topography, creating a path to designing improved bioactive medical implant surfaces. Because topographies are also able to instruct cells at the nanoscale, it was the second aim of the thesis to extend the screening of micro-topographies for cell response to nano-topographies. For this, we developed the Nano-TopoChip which contains more than 1200 randomly generated surface topography designs with lateral dimensions between 100 nm and 2 µm, which is more than 50 times smaller than the micro-Topochip. The Nano-TopoChip was used to study the effects of nano-topography on cell morphology by inference of the relationship between surface design parameters and cell morphological parameters.