Thermo-responsive microcarriers based on poly(N-isopropylacrylamide)

•Microcarrier cell culture systems are useful for cell culture amplification.•Surface PNIPAAm releases cells by temperature adjustment.•This review presents methods to prepare PNIPAAm microcarriers.•The efficiency of methods is compared.

Microcarrier cell culture systems provide an attractive alternative to the conventional monolayer cell culture for cell amplification, due to their high surface area-to-volume ratio. Unlike enzymatic methods for removing cells from microcarriers after cell culture, which can lead to irreversible damage of the cells, microcarriers which release cells by temperature adjustment have been developed. This was achieved by grafting a temperature-responsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), on the microcarrier surface. This review comprehensively presents various methods to prepare such thermo-responsive microcarriers based on PNIPAAm. These methods include the grafting-to technique, grafting-from technique, grafting-through technique, along with methods leading to PNIPAAm hydrogel beads, seeded polymerization, and non-covalent adsorption. The methods for controlling PNIPAAm grafting density, molecular weight and molecular architecture are also outlined. Further, the efficiency of cell attachment, proliferation and thermally-induced detachment of such thermo-responsive microcarriers is introduced and compared.

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