Length-Scale Mediated Adhesion and Directed Growth of Neural Cells by Surface-Patterned Poly(ethylene glycol) Hydrogels

摘要

We engineered surfaces that permit the adhesion and directed growth of neuronal cell processes – axons – but that prevent the adhesion of astrocytes. This effect was achieved based on the spatial distribution of cell-repulsive poly(ethylene glycol) [PEG] nanohydrogels patterned on an otherwise cell-adhesive substrate. Patterns were identified that promoted cellular responses ranging from complete non-attachment, selective attachment, and directed growth at both cellular and subcellular length scales. At the highest patterning density where the individual nanohydrogels almost overlapped, there was no cellular adhesion. As the spacing between individual nanohydrogels was increased, patterns were identified where axons could grow on the adhesive surface between nanohydrogels while astrocytes were unable to adhere. Patterns such as lines or arrays were identified that could direct the growth of these subcellular neuronal processes. At higher nanohydrogel spacings, both neurons and astrocytes adhered and grew in a manner approaching that of unpatterned control surfaces. Patterned lines could once again direct growth at cellular length scales. Significantly, we have demonstrated that the patterning of nanoscale cell-repulsive features at microscale lengths on an otherwise cell-adhesive surface can differently control the adhesion and growth of cells and cell processes based on the difference in their characteristic sizes. This concept could potentially be applied to an implantable nerve-guidance device that would selectively enable regrowing axons to bridge a spinal-cord injury without interference from the glial scar.