Cell Attachment–Detachment Control on Temperature-Responsive Thin Surfaces for Novel Tissue Engineering

Abstract

Temperature-responsive intelligent surfaces, prepared by the modification of an interface mainly with poly(N-isopropylacrylamide) and its derivatives, have been investigated. Such surfaces exhibit temperature-responsive hydrophilic/hydrophobic alterations with external temperature changes, which, in turn, result in thermally modulated attachment and detachment with cells. The advantage of this system is that cells cultured on such temperature-responsive surfaces can be recovered as single cells and/or confluent cell sheets, while keeping the deposited extracellular matrix intact, simply by lowering the temperature without conventional enzymatic treatment. Here, we focus and compare various methods of producing temperature-responsive surfaces for controlling cell attachment/detachment. Spontaneous cell attachment and detachment using several types of temperature-responsive surfaces are mentioned and various effects, such as film thickness and polymer conformation, are discussed. In addition, the development of the next generation of temperature-responsive surfaces using modifications of the polymer coating to allow for rapid cell recovery is summarized.

Thermoresponsive Polymers for Biomedical Applications

“…In the first application, the thermoresponsive ability of the polymers is used to regulate the cells' attachment and detachment from a surface [61][62][63][64]. In fact, in one study, the polymer surface was even reusable for repeated cell culture [65].…”

Tunable Stimuli-Responsive Polymers for Cell Sheet Engineering

“…Also it is essential that the cells are easily detached from the substrate after it has grown. Conventionally enzymatic proteolysis of extracellular matrix (ECM) with trypsin or other proteolytic enzymes used to detach cells from substrates which can affect cell re-adhesion, cell viability etc (Kumashiro et al, 2010). Thermoresponsive polymers are of great interest in tissue engineering applications specifically in cell sheet detachment.…”

Thermoresponsive Substrates used for the Expansion of Human Mesenchymal Stem Cells and the Preservation of Immunophenotype

“…[10] Studies have shown that cells attach and therefore proliferate poorly on thick or bulk pNIPAm coatings and many studies report a coating thickness limitation above which there is a 4 dramatic reduction in the number of cells attaching to the polymer surface [12][13][14][15][16]. In studies where pNIPAm was covalently grafted for this purpose, this thickness limitation is in the order of tens of nanometers with the exception of coatings formed via plasma polymerization [12,[17][18][19]. Our previous studies using spin coated commercially sourced polymer found that there was no relationship between the thickness of the film produced and successful cell attachment and proliferation within the thickness-scale employed (> 30 nm to < 2000 nm) [10].…”