Photo-Dimerization Induced Dynamic Viscoelastic Changes in ABA Triblock Copolymer-Based Hydrogels for 3D Cell Culture

Abstract

Cells sense and respond not only to biochemical signals but also to biophysical signals (e.g., matrix elasticity). In addition to matrix elasticity, recent studies have revealed that viscoelasticity (e.g., stress relaxation) significantly affects cellular functions, such as spreading, proliferation, and differentiation. Herein, we describe a cytocompatible and dynamic hydrogel that is comprised of well-defined ABA triblock copolymers, which enable significant changes of viscoelastic properties solely by UV light irradiation. The A block contains N-isopropylacrylamide and an acrylate monomer with a coumarin side chain, whereas the B block is biocompatible poly(ethylene oxide). The triblock copolymer forms a physically cross-linked hydrogel under physiologically relevant conditions. However, under UV light irradiation, the viscoelasticity of the hydrogel is dynamically modulated due to the photodimerization of coumarin moieties. After UV illumination, rheological properties of the hydrogel are drastically different, indicating the formation of chemical cross-linking points in the hydrogel. Finally, we demonstrate that the dynamic change in the viscoelasticity of the hydrogel has a significant influence on the behavior of encapsulated cells.

Programmed Multiresponsive Hydrogel Assemblies with Light‐Tunable Mechanical Properties, Actuation, and Fluorescence

“…The G′ value for the photocrosslinked gel (390 Pa) is five times higher than that for the parent nonirradiated gel (77 Pa) and decreases to 72 Pa when photocleaved (Figure G). Values of tan δ (= G″ / G′ ) less than 1.0 are signatures of elastic behavior and are lowest for the photocrosslinked gel. Hence, photocrosslinking causes major mechanical property changes.…”

3D Spatiotemporal Mechanical Microenvironment: A Hydrogel‐Based Platform for Guiding Stem Cell Fate

“…To address this challenge, a well‐defined P(NIPAAm‐ r ‐CA)‐ b ‐PEO‐ b ‐P(NIPAAm‐ r ‐CA) triblock copolymer (CA, coumarin acrylate) was synthesized. When the polymer concentration was higher than the chain‐overlap concentration, this triblock copolymer formed a physically crosslinked hydrogel upon heating, showing a stress relaxation behavior ( Figure A) . Alternatively, a type of hydrazine‐crosslinked PEG hydrogel with viscoelastic properties was also developed (Figure B) .…”

“…b) Stress relaxation tests for the hydrogel at 37 °C. A) Reproduced with permission . Copyright 2016, American Chemical Society.…”

Bioinspired glycosaminoglycan hydrogels via click chemistry for 3D dynamic cell encapsulation

“…For example, MSCs could sense the differences in mechanical environments and initiate the mechanotransduction pathways, which ultimately would affect cell fate and distinct lineage differentiation . Using hydrogels that stiffen or soften post cell encapsulation, pioneering studies have elucidated the importance of timing and magnitude of matrix stiffness changes in the regulation of cell behaviors and functions . However, it remains largely unknown whether and how cells react to temporal hydrogel gelation during 3D encapsulation, which involves a transition of cell microenvironment from a viscoelastic fluid to an elastic solid.…”