A biocompatible method of controlled retrieval of cell-encapsulating microgels from a culture plate

We report a biocompatible method of selectively retrieving 3-D cell-encapsulating hydrogel microstructures from a culture substrate. First, poly(l-lysine)/hyaluronic acid (PLL/HA) polyelectrolyte multilayers (PEMs) with methacrylated chitosan (GMA-Chi) on top were formed on an ITO substrate. Then, a cell-encapsulating hydrogel micropattern was formed; a HepG2 cell-encapsulating heparin-based hydrogel micropattern was fabricated by thiol-ene photopolymerization. The application of an oxidative potential of 2 V resulted in the detachment of the cell-encapsulating hydrogels by the dissolution of PEMs. The time of complete retrieval of the hydrogels was controllable by modulating the number of PEM layers. The applied potential did not affect the viability or the function of the cells in the entire hydrogels. In contrast, when a reductive electrochemical potential (-1.8 V) was applied to a silane-modified ITO to release cell-encapsulating hydrogels by the desorption of silane [Chem. Commun., 2009, 5865], extensive cell death at the bottom of the hydrogel adjacent to the electrode was observed.