TY - JOUR

T1 - On the foundation of thermal “Switching”

T2 - The culture substrate governs the phase transition mechanism of thermoresponsive brushes and their performance in cell sheet fabrication

AU - Stöbener, Daniel D.

AU - Weinhart, Marie

N1 - Funding Information: This research was funded by the Federal Ministry of Education and Research Germany (BMBF) [Grant number FKZ: 13N13523 ].

PY - 2021/12

Y1 - 2021/12

N2 - Thermally “switchable” poly(glycidyl ether) (PGE) brushes constitute effective coatings for the temperature-triggered harvest of confluent cell sheets. Based on a simple “grafting-to” approach, such coatings can be tethered to various applied plastic culture substrate materials. Herein, we elucidate the self-assembly of PGE brushes with tunable grafting densities up to 0.12 and 0.22 chains nm−2 on polystyrene (PS) and tissue culture PS (TCPS), respectively. In terms of temperature-dependent wettability and protein adsorption, we found that brushes exhibit distinct grafting density-dependent properties which correlate with their cell sheet fabrication performance. In addition, temperature-ramped quartz-crystal microbalance with dissipation (QCM-D) measurements revealed marked substrate-specific PGE phase transitions which allowed us to deduce comprehensive switching mechanisms. Thus, we demonstrate that brushes tethered to hydrophilic TCPS (contact angle (CA) ∼ 60°) undergo a “cushioned” transition comprising a non-switchable, hydrated basal layer as well as a switchable top layer which regulates cell sheet detachment. In contrast, PGE brushes tethered to PS undergo a “grounded” transition which is substantially influenced by the dehydrating effect of the less hydrophilic PS substrate (CA ∼ 90°). These divergent phase transition mechanisms give rise to a broad scope in cell sheet fabrication performance, yielding staggered detachment times within a 30 min to 3 h range. Hence, we emphasize the importance of a detailed knowledge on the effect of applied culture substrates on the thermal switchability and phase transition characteristics of thermoresponsive brush coatings to accomplish an optimized design for functional cell culture dishes. Statement of significance: As the first comparative study of its kind, we elucidate the substrate-dependent thermal switchability of thermoresponsive brush coatings and evaluate their grafting density-dependent phase transition mechanism and its effect on cell sheet fabrication performance.

AB - Thermally “switchable” poly(glycidyl ether) (PGE) brushes constitute effective coatings for the temperature-triggered harvest of confluent cell sheets. Based on a simple “grafting-to” approach, such coatings can be tethered to various applied plastic culture substrate materials. Herein, we elucidate the self-assembly of PGE brushes with tunable grafting densities up to 0.12 and 0.22 chains nm−2 on polystyrene (PS) and tissue culture PS (TCPS), respectively. In terms of temperature-dependent wettability and protein adsorption, we found that brushes exhibit distinct grafting density-dependent properties which correlate with their cell sheet fabrication performance. In addition, temperature-ramped quartz-crystal microbalance with dissipation (QCM-D) measurements revealed marked substrate-specific PGE phase transitions which allowed us to deduce comprehensive switching mechanisms. Thus, we demonstrate that brushes tethered to hydrophilic TCPS (contact angle (CA) ∼ 60°) undergo a “cushioned” transition comprising a non-switchable, hydrated basal layer as well as a switchable top layer which regulates cell sheet detachment. In contrast, PGE brushes tethered to PS undergo a “grounded” transition which is substantially influenced by the dehydrating effect of the less hydrophilic PS substrate (CA ∼ 90°). These divergent phase transition mechanisms give rise to a broad scope in cell sheet fabrication performance, yielding staggered detachment times within a 30 min to 3 h range. Hence, we emphasize the importance of a detailed knowledge on the effect of applied culture substrates on the thermal switchability and phase transition characteristics of thermoresponsive brush coatings to accomplish an optimized design for functional cell culture dishes. Statement of significance: As the first comparative study of its kind, we elucidate the substrate-dependent thermal switchability of thermoresponsive brush coatings and evaluate their grafting density-dependent phase transition mechanism and its effect on cell sheet fabrication performance.

KW - Block copolymer adsorption

KW - Cell sheet

KW - Enzyme-free

KW - Structure-property correlation

KW - Volume phase transition temperature

UR - http://www.scopus.com/inward/record.url?scp=85115777435&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2021.09.012

DO - 10.1016/j.actbio.2021.09.012

M3 - Article

AN - SCOPUS:85115777435

VL - 136

SP - 243

EP - 253

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

ER -