Thermoresponsive Polymer Micropatterns Fabricated by Dip-Pen Nanolithography for a Highly Controllable Substrate with Potential Cellular Applications

Abstract

We report a novel approach for patterning thermoresponsive hydrogels based on N,Ndiethylacrylamide (DEAAm) and bifunctional Jeffamine ED-600 by dip-pen nanolithography (DPN). The direct writing of micron-sized thermoresponsive polymer spots was achieved with efficient control over feature size. A Jeffamine-based ink prepared through the combination of organic polymers, such as DEAAm, in an inorganic silica network was used to print thermosensitive arrays on a thiol-silanised silicon oxide substrate. The use of a Jeffamine hydrogel, acting as a carrier matrix, allowed a reduction in the evaporation of ink molecules with high volatility, such as DEAAm, and facilitated the transfer of ink from tip to substrate. The thermoresponsive behaviour of polymer arrays which swell/de-swell in aqueous solution in response to a change in temperature was successfully characterised by atomic force microscopy (AFM) and Raman spectroscopy: a thermally-induced change in height and hydration state was observed, respectively. Finally, we demonstrate that cells can adhere to and interact with these dynamic features and exhibit a change in behaviour when cultured on the substrates above and below the transition temperature of the Jeffamine/DEAAm thermoresponsive hydrogels. This 3 demonstrates the potential of these micropatterned hydrogels to act as a controllable surface for cell growth.

Fabrication, chemical modification, and topographical patterning of reactive gels assembled from azlactone‐functionalized polymers and a diamine

“…First, it is amphiphilic and, thus, permits formation of gels in organic solvents followed by exchange of the organic solvent for aqueous media to form hydrogels (see sections below). Jeffamine is also compatible with cells and other biological species and has been used in a variety of biomaterials scaffolds . Although several different organic solvents (e.g., THF, CH 2 Cl 2 , CHCl 3 , DMSO, etc.)…”

High-Throughput Methods in the Discovery and Study of Biomaterials and Materiobiology

“…412 To increase the number of materials that may be investigated, polymer microarrays were developed where small polymer spots in the μm-range afford high density on a substrate. A large variety of techniques, such as but not limited to, photolithography, 413 soft-lithography, 414 microfluidics, 415 nanolithography, 416 contact pin, 417 and inkjet 418 automated printing, and on-chip synthesis, 419 have been used to fabricate microarrays. These approaches vary in their flexibility; from the type and range of defined biomaterials, they are able to support, to their solvent compatibility, their freedom to control object shape, and their polymerization strategies.…”

Evolution of Dip-Pen Nanolithography (DPN): From Molecular Patterning to Materials Discovery

“…In the fields of biology and medicine, many researchers are working to use artificial microarrays to study and control cellular behavior, such as adhesion, orientation, migration, and differentiation. − As unique nanofabrication techniques, DPN, PPL, and DNL have been widely used to fabricate bioarrays for such purposes. − …”

“…In short, parallel DPN played a key role in the fabrication of functional protein matrices for studying cellular behavior. In 2016, Laing et al directly patterned thermoresponsive, micron-sized polymer hydrogels based on N,N-diethylacrylamide (DEAAm) and bifunctional Jeffamine ED-600 using DPN and employed these surfaces to control cellular behavior . This thermally controllable microarray possessed dynamic features that swelled or collapsed with changing temperature.…”