Injectable Hydrogels with In Situ Double Network Formation Enhance Retention of Transplanted Stem Cells.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 1 wileyonlinelibrary.com in a shear-thinning, physical hydrogel can provide mechanical protection that prevents cell membrane damage during injection. [ 8 ] Weak hydrogels with shear moduli < 50 Pa were previously found to offer the best protection; however, these materials typically biodegrade too quickly (within 1–2 weeks) to support long-term cell survival in a 3D matrix. [ 8,16,21–23 ] Therefore, it has been challenging to design a hydrogel that can simultaneously address both causes of low cell retention in a single gel formulation. Toward this end, we aim to design an injectable hydrogel that undergoes two different physical crosslinking mechanisms: (1) weak, heterodimeric, molecular-recognition ex vivo to provide mechanical cell protection during injection and (2) additional crosslinking in vivo induced by thermoresponsive formation of a reinforcing network to support longterm cell survival within a 3D matrix. While several naturally derived hydrogel materials have been used for injectable cell transplantation, including alginate, [ 8 ]