Poly(N-isopropylacrylamide): experiment, theory and application

Hydrogels for tissue engineering.

https://imechanica.org/files/Qiu_environmental_sensitive_hydrogel.pdf

Environment-sensitive hydrogels for drug delivery

Foreign body reaction to biomaterials.

Hydrogels in pharmaceutical formulations.

MANY polymeric hydrogels undergo abrupt changes in volume in response to external stimuli such as changes in solvent composition1, pH2, electric field3 and temperature4–6. For several of the potential applications of these materials, such as 'smart' actuators, a fast response is needed. The kinetics of swelling and de-swelling in these gels are typically governed by diffusion-limited transport of the polymeric components of the network in water, the rate of which is inversely proportional to the square of the smallest dimension of the gel7–9. Several strategies have been explored for increasing the response dynamics10–14, such as introducing porosity14. Here we show that we can induce rapid de-swelling of a polymer hydrogel by tailoring the gel architecture at the molecular level. We prepare a crosslinked hydrogel in which the polymer chains bear grafted side chains; the latter create hydrophobic regions, aiding the expulsion of water from the network during collapse. Whereas similar gels lacking the grafted side chains can take more than a month to undergo full de-swelling, our materials collapse in about 20 minutes.

Comb-type grafted hydrogels with rapid deswelling response to temperature changes

Poly(N-isopropyl acrylamide) (PIPAAm) demonstrated a fully expanded chain conformation below 32 degrees C and a collapsed, compact conformation at high temperatures. This unique temperature responsive polymer was grafted onto surfaces of commercial polystyrene dishes and used as temperature switches for creating hydrophilic surfaces below 32 degrees C and hydrophobic surfaces above 32 degrees C. Cell attachment and the growth of bovine endothelial cells and rat hepatocytes on PIPAAm-grafted surfaces at 37 degrees C demonstrated similar behavior to the commercialized culture dishes. Both cell types were observed to detach from the PIPAAm-grafted surface simply by reducing the temperature below the polymer transition temperature (collapse). Cells recovered by this method maintained substrate adhesivity, growth, and secretion activities nearly identical to those found in primary cultured cells in contrast to the compromised function found in cultured cells damaged by trypsinization. These results provide strong evidence that PIPAAm-grafted surfaces, as thermal switches are very effective for reversing cell attachment and detachment without cell damage. Properties of cell culture surfaces can be readily transformed by this technique reversibly into hydrophilic and hydrophobic coatings of PIPAAm-grafted polymers.

A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylamide).

Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells

Mechanism of cell detachment from temperature-modulated, hydrophilic–hydrophobic polymer surfaces

Doxorubicin-loaded poly(ethylene glycol)–poly(β-benzyl-l-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance

Yasuhisa Sakurai

Papers

Comb-type grafted hydrogels with rapid deswelling response to temperature changes

A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylamide).

Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells

Mechanism of cell detachment from temperature-modulated, hydrophilic–hydrophobic polymer surfaces

Doxorubicin-loaded poly(ethylene glycol)–poly(β-benzyl-l-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance