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

文献索引：Adv. Healthc. Mater. 4(2) , 237-44, (2015)

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摘要

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.