Advanced Healthcare Materials 2015-01-28

Supramolecular hydrogels for long-term bioengineered stem cell therapy.

Junseok Yeom, Su Jin Kim, Hyuntae Jung, Hong Namkoong, Jeonga Yang, Byung Woo Hwang, Kyunghoon Oh, Kimoon Kim, Young Chul Sung, Sei Kwang Hahn

Index: Adv. Healthc. Mater. 4(2) , 237-44, (2015)

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Abstract

Synthetic hydrogels have been extensively investigated as artificial extracellular matrices (ECMs) for tissue engineering in vitro and in vivo. Crucial challenges for such hydrogels are sustaining long-term cytocompatible encapsulation and providing appropriate cues at the right place and time for spatio-temporal control of the cells. Here, in situ supramolecularly assembled and modularly modified hydrogels for long-term engineered mesenchymal stem cell (eMSC) therapy are reported using cucurbit[6]uril-conjugated hyaluronic acid (CB[6]-HA), diaminohexane conjugated HA (DAH-HA), and drug-conjugated CB[6] (drug-CB[6]). The eMSCs producing enhanced green fluorescence protein (EGFP) remain alive and emit the fluorescence within CB[6]/DAH-HA hydrogels in mice for more than 60 d. Furthermore, the long-term expression of mutant interleukin-12 (IL-12M) by eMSCs within the supramolecular hydrogels results in effective inhibition of tumor growth with a significantly enhanced survival rate. Taken together, these findings confirm the feasibility of supramolecular HA hydrogels as 3D artificial ECMs for cell therapies and tissue engineering applications.© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.