Temperature-responsive intelligent interfaces for biomolecular separation and cell sheet engineering

Abstract

Temperature-responsive intelligent surfaces, prepared by the modification of an interface with poly(N-isopropylacrylamide) and its derivatives, have been used for biomedical applications. Such surfaces exhibit temperature-responsive hydrophilic/hydrophobic alterations with external temperature changes, which, in turn, result in thermally modulated interactions with biomolecules and cells. In this review, we focus on the application of these intelligent surfaces to chromatographic separation and cell cultures. Chromatographic separations using several types of intelligent surfaces are mentioned briefly, and various effects related to the separation of bioactive compounds are discussed, including wettability, copolymer composition and graft polymer architecture. Similarly, we also summarize temperature-responsive cell culture substrates that allow the recovery of confluent cell monolayers as contiguous living cell sheets for tissue-engineering applications. The key factors in temperature-dependent cell adhesion/detachment control are discussed from the viewpoint of grafting temperature-responsive polymers, and new methodologies for effective cell sheet culturing and the construction of thick tissues are summarized.

Tunable Stimuli-Responsive Polymers for Cell Sheet Engineering

“…Profilometry is another method to visualize the surface morphology and the quantitative analysis of surface roughness and thickness from the surface profile measurement . Determination of thickness from ellipsometry and surface plasmon resonance is very difficult because of the similarity in refractive index of both PNIPAAm and polymeric substrates (Nagase et al, 2009). Biological evaluations of thermoresponsive surface is the most important characterization technique for cell sheet engineering and are done by cytotoxicity analysis, cell activity measurement, thermoresponsive efficacy, viability analysis and cell sheet characterization etc.…”

“…Electron beam method facilitates even, thin grafting and the large scale production of temperature responsive culture dishes even though it is expensive. The thickness is controlled by monomer concentration and radiation energy (Nagase et al, 2009). …”

“…Photopolymerisation and photografting of PNIPAAm is done on TCPS by UV irradiation (365 nm for 5 to 30 min) using photo initiators such as benzophenone (Nagase et al, 2009). …”

Thermally Responsive Amphiphilic Conetworks and Gels Based on Poly(N-isopropylacrylamide) and Polyisobutylene

“…Examples for the biomedical applications include controlled drug delivery, 5 biomaterials 6 , cell culture surfaces 7 , tissue engineering 8 or biomolecule separation 9,10 , while some other uses, such as core/shell nanoparticles 11 or intelligent glass 12 are also interesting possibilities. However, one substantial disadvantage of the traditionally synthesized, pure PNiPAAm gels from practical point of view is related to the fact that these are mechanically not stable, soft, untreatable and nontransparent materials.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12] This polymer in aqueous solution, as well as its gel in swollen state, is sensitive to the temperature of the environment. 2,3 Above a certain temperature, the hydrophilic PNiPAAm changes its philicity, rapidly becomes hydrophobic, 4 and the polymer and the gel precipitates and collapses, respectively.…”