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• Review •

Intelligent Cell Detachment Materials Based on Poly(N-Isopropylacrylamide)

Liu Dan, Wang Tao, Liu Xinxing, Wang Chaoyang, Tong Zhen   

  1. Research Institute of Materials Science, South China University of Technology, Guangzhou 510640, China
  • Received: Revised: Online: Published:
  • Contact: Tong Zhen E-mail:mcztong@scut.edu.cn
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Poly(N-isopropylacrylamide) (PNIPAm) exhibits temperature-response due to the hydrophilic-hydrophobic transition in aqueous solutions and hydrogels at the lower critical solution temperature (LCST). This characteristic has been used for cell proliferation at the hydrophobic PNIPAm surface and spontaneous detachment of the cell sheet upon the hydrophilic transition at LCST. In this review, several methods were introduced to prepare temperature-responsive substrates for the cell culture, proliferation and detachment, including electron beam irradiation grafting, plasma treatment grafting, living radical polymerization on surface, and hydrogels. The two-step mechanism of spontaneous cell detachment from the PNIPAm modified substrates was briefly discussed considering the hydrophilic-hydrophobic transition and the cells' shape change induced by the cell metabolism. The limitation of this mechanism to other sorts of cells was pointed out. Some approaches to accelerate the spontaneous detachment of cells from PNIPAm modified substrates for rapid cell harvest were described, such as copolymerization of PNIPAm to increase hydrophilicity below the LCST, PNIPAm grafted porous membrane for fast water diffusion, poly(ethylene glycol)-co-PNIPAm grafted porous membrane for increasing hydrophilicity, and poly(vinylidene difluoride) membrane assistant cell transfer. Cell sheets harvested from the temperature-responsive PNIPAm substrates by lowering the temperature without enzymatic treatment retained their intact structure with the cell-cell junctions and deposited extracellular matrices (ECM), which promised applications in tissue repair.

Contents
1 Introduction
2 Preparation of temperature-responsive cell culture substrates
2.1 Electron beam irradiation grafting
2.2 Plasma treatment grafting
2.3 Living radical polymerization on surface
2.4 Hydrogels
3 Mechanism of cell detachment
4 Methods for accelerating cell detachment
4.1 Copolymerization of PNIPAm
4.2 PNIPAm grafted porous membrane
4.3 PEG-co-PNIPAm grafted porous membrane
4.4 PVDF membrane assistant cell transfer
5 Conclusions and perspectives

CLC Number: 

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