Supramolecular hydrogels for long-term bioengineered stem cell therapy

Abstract

Synthetic hydrogels have been extensively investigated as artifi cial 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 spatiotemporal control of the cells. Here, in situ supramolecularly assembled and modularly modifi ed 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 fl uorescence protein (EGFP) remain alive and emit the fl uorescence 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 signifi cantly enhanced survival rate. Taken together, these fi ndings confi rm the feasibility of supramolecular HA hydrogels as 3D artifi cial ECMs for cell therapies and tissue engineering applications.