Neuron guidance by biomimetic topographical cues.

摘要

My graduate work examined the reaction of neuronal cells to the shape of their extracellular environment. Over the last century, many studies have confirmed that external topography has a profound influence on cellular behavior. Using geometric, rectangular repeating grooves with size ranges in the tens of micrometers, we were the first to describe "cellular bridging" in which a variety of anchorage-dependent cell types including primary rat and human cell cultures as well as a variety of immortal rat, mouse, and human cell lines extended from one plateau to an adjacent plateau of a multiple grooved substrate without underlying support. Extending our research to more complex shapes, we developed a platform technology based on a two-stage replica molding approach that is capable of reproducing adherent cellular shapes at a macro-, micro-, and nano-scale in various polymeric substrates and thus create cell-shaped polymeric surfaces. This allowed us to separate the presentation of cellular shape from cellular biochemistry and characterize cellular behavior in response to cellular shape in the absence of other heterogeneous cellular cues that are inherent to cell-cell interactions in co-cultures. Utilizing these novel materials, we were able to show that cellular topography is capable of enhancing adhesion, motility, and alignment in the absence of other directional cues. Pilot experiments with nerve guidance channels incorporating cell-shaped biomimetic topography showed increased cellular migration and outgrowth from dorsal root ganglion explants on surfaces with aligned biomimetic topography when compared to topographically homogeneous controls. The results of this research inform efforts at the basic science level by enabling the deconstruction of cellular environments beyond previous capabilities and quantifying the contribution of cellular and extracellular matrix shape to cellular behavior. These results also open new avenues to controlling cellular response to implant surfaces. Currently, these techniques and approaches are continued and expanded by my colleagues to encompass different organ systems such as the vascular system and the control of differentiation of stem cells by cellular topography.