Length-scale mediated adhesion and directed growth of neural cells by surface-patterned poly(ethylene glycol) hydrogels

Abstract

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.

Peripheral Nerve Grafts and Chondroitinase ABC Application Improves Functional Recovery After Complete Spinal Cord Transection

“…This creates an anatomical gap that axons are unable to cross. There have been several approaches used to bridge this anatomical gap, including poly(lactide-co-glycolide) (PLGA) scaffolds [9,10], Schwann cells [11], poly(ethylene glycol) hydrogels [12,13], agarose scaffolds [14,15], and peripheral nerve grafts (PNGs) [16][17][18][19][20][21][22]. PNGs are a living tissue containing several growth factors that have been shown to promote axonal growth, and cytokines that modulate inflammation [23,24].…”

Neural cell alignment by patterning gradients of the extracellular matrix protein laminin

“…Our approach does not require any background passivation step, whereas many other methods use surface pre-treatment with an anti-cell-adhesion layer such as poly(-ethylene glycol) to enhance compositional contrast [51,52] or by creating double-cue opposing gradients [19]. Here, we have exploited the surface tension feature of the polystyrene substrate (contact angle ¼ 67.38+1.58) to maintain the cell culture confinement for a prolonged time in the presence of serum-containing medium.…”

Surface Treatments to Modulate Bioadhesion: A Critical Review

“…Krsko et al [177] considered neuronal cells and employed electron beam technologies to surface pattern poly(ethylene glycol) hydrogels to discriminate between eukaryotic cells and bacterial cells. This is highly significant as it shows that these technologies can be used to aid in the differentiation between different cell types which tend to have very different properties such as adhesion mechanisms and cell sizes.…”

“…This is highly significant as Staphylococcus aureus, Staphylococcus epidermis and Pseudomonas aeruginosa are all known bacterial cells which give rise to implications in orthopaedic implants. One can then see that by the further application of the work conducted by Krsko et al [177] the adhesion and growth of these bacterial cells can be reduced through the patterning of materials using electron beam technologies.…”