Adhesion, proliferation, and detachment of various cell types on thermoresponsive microgel coatings

Abstract

Cutting-edge biomedical applications require increasingly complex and fastidious cell systems, for example, various classes of primary or stem cells. Their cultivation, however, still differs little from 30 years ago. This especially applies to the use of indiscriminative proteases for nonspecific cell detachment. A far more gentle alternative changes the adhesive properties of the cell culture substrates through coatings based on thermoresponsive polymers. Such polymers mediate cell adhesion at 37°C, but become repulsive upon a cell-compatible temperature drop to, for example, 32°C. While the high functionality of this method has already been well proven, it must also be easy and reproducible to apply. Here, we emphasize the potential of standard cell culture materials coated by spraying with thermoresponsive microgels for routine cultivation and beyond.On these surfaces, we successfully cultivated and detached various cell types, including induced pluripotent stem cells and cells in serum-free culture. In addition, we evaluated the compatibility of the microgel-sprayed surfaces with adhesion-promoting proteins, which are essential for, for example, stem cells or neuronal cells. Finally, we demonstrate that the microgel surfaces do not impair proliferation and show their long-term stability. We conclude that for cell detachment, thermoresponsive cell culture substrates can fully substitute proteases, like trypsin, by employing a comparably straightforward protocol that is compatible with many industrial processing lines.

A review of stimuli-responsive polymer-based gating membranes

“…9 that can be employed in tunable coatings to trigger the adsorption/desorption of biological cells. [19][20][21] A similar application based on chains (as opposed to microgel particles) focusing on proteins has been proposed by Ulbricht and Yang. 22 Besides the monomer chemistry, the network connectivity also impacts macroscopic properties, and thus possibly gating.…”

Unusual Shell Morphologies of Responsive Amino Core‐Shell Microgels Induced by pH During Shell Synthesis

“…Therefore, the pH responsivity makes the microgels also more sensitive toward changes of the ionic strength. [9][10][11] In the past, responsive microgels have proven to be useful for a variety of different applications, like smart surface coatings, [12,13] drug delivery, [14][15][16] optical devices, [17] membranes, [18] catalysis, [19,20] or as nanosensors. [21] Especially core-shell microgels that have a more complex architecture are of rising interest for future applications.…”

Synthesis and Characterization of Catechol-Containing Polyacrylamides with Adhesive Properties

“…One strategy to prepare synthetic polymers with catechol moieties on the side chains is free radical polymerization [12,14,[17][18][19]. Recent smart coating materials mostly contain acrylamides as co-monomers, such as poly(Nisopropylacrylamide), to create functionalized surfaces, e.g., with structured nanopillar array properties [20] and thermoresponsive hydrophobic interaction [21] or stimulatory properties [22] such as cell attachment/detachment [23].…”