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A Microgel Construction Kit for Bioorthogonal Encapsulation and pH‐Controlled Release of Living Cells
Authors:Dirk Steinhilber  Torsten Rossow  Dr Stefanie Wedepohl  Florian Paulus  Dr Sebastian Seiffert  Prof?Dr Rainer Haag
Institution:1. Freie Universit?t Berlin, Institute for Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin (Germany);2. Helmholtz‐Zentrum Berlin, F‐ISFM Soft Matter and Functional Materials, Berlin (Germany);3. Helmholtz Virtuelles Institut – Multifunctional Biomaterials for Medicine, Helmholtz‐Zentrum Geesthacht, Teltow (Germany)
Abstract:pH‐Cleavable cell‐laden microgels with excellent long‐term viabilities were fabricated by combining bioorthogonal strain‐promoted azide–alkyne cycloaddition (SPAAC) and droplet‐based microfluidics. Poly(ethylene glycol)dicyclooctyne and dendritic poly(glycerol azide) served as bioinert hydrogel precursors. Azide conjugation was performed using different substituted acid‐labile benzacetal linkers that allowed precise control of the microgel degradation kinetics in the interesting pH range between 4.5 and 7.4. By this means, a pH‐controlled release of the encapsulated cells was achieved upon demand with no effect on cell viability and spreading. As a result, the microgel particles can be used for temporary cell encapsulation, allowing the cells to be studied and manipulated during the encapsulation and then be isolated and harvested by decomposition of the microgel scaffolds.
Keywords:click chemistry  gels  hydrolysis  pH‐cleavable linkers  reversible cell encapsulation
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