Fabrication of Micropatterned Dipeptide Hydrogels by Acoustic Trapping of Stimulus‐Responsive Coacervate Droplets

Abstract

Acoustic standing waves offer an excellent opportunity to trap and spatially manipulate colloidal objects. This noncontact technique is used for the in situ formation and patterning in aqueous solution of 1D or 2D arrays of pH-responsive coacervate microdroplets comprising poly(diallyldimethylammonium) chloride and the dipeptide N-fluorenyl-9-methoxy-carbonyl-D-alanine-D-alanine. Decreasing the pH of the preformed droplet arrays results in dipeptide nanofilament self-assembly and subsequent formation of a micropatterned supramolecular hydrogel that can be removed as a self-supporting monolith. Guest molecules such as molecular dyes, proteins, and oligonucleotides are sequestered specifically within the coacervate droplets during acoustic processing to produce micropatterned hydrogels containing spatially organized functional components. Using this strategy, the site-specific isolation of multiple enzymes to drive a catalytic cascade within the micropatterned hydrogel films is exploited.

Tailoring Gelation Mechanisms for Advanced Hydrogel Applications

“…Gluconoδ-lactone was used to slowly lower the pH and trigger the formation of dipeptide hydrogels. [201] Alternatively, techniques such as mask-based photolithography, single-photon laser-scanning lithography, and multiphoton laser-scanning lithography have been used for high-resolution, chemical modification of preformed hydrogels. [111,134] Examples include the use of thiol-ene chemistry to photopattern arginylglycylaspartic acid peptides onto nanofibrous hydrogels to control cellular adhesion, [202] and the use of oxime ligation and o-nitrobenzyl ester photoscission for the attachment and release of proteins for reversible stem cell differentiation.…”

“…B) Schematic of a strategy by Nichols et al in which acoustic standing waves were used to trap pH-responsive polymer-dipeptide coacervate microdroplets. [201] Images of patterned dipeptide supramolecular hydrogels generated using (ii) 1D and (ii) 2D ultrasound standing waves. Scale bars: main = 5 mm and inset = 1 mm.…”

“…Reproduced under the terms of the Creative Commons CC-BY-NC license. [201] Copyright 2018, The Authors, published by Wiley-VCH Verlag GmbH & Co. KGaA. C) (i) Schematic of work by Liu et al describing light-mediated stiffness patterning within protein/PEG-based hydrogels.…”

Using Remote Fields for Complex Tissue Engineering

“…Moreover, the forces used for patterning are proportional to the object volume and thus it can be extremely challenging to pattern nanoscale entities, such as biochemical factors or matrix fibers. This limitation has led to the development of strategies that use microscale carriers to host biomolecular cargo or template material fabrication [55,56]. An alternative approach is the use of focused ultrasound that can provide highly localized stimuli capable of modulating different tissue engineering components.…”

“…The final challenge is to improve the accessibility of remote field instrumentation. Apparatus is often assembled in house [45,55], however, the need for users to assemble and operate their own devices restricts usage to a small number of groups with specialist expertise. This situation could be alleviated by more active dissemination of academic knowledge through protocols and methods papers, or by making devices available through user collaboration or product commercialization.…”