Shaping and Patterning Supramolecular Materials─Stem Cell-Compatible Dual-Network Hybrid Gels Loaded with Silver Nanoparticles

Hydrogels with spatio-temporally controlled properties are appealing materials for biological and pharmaceutical applications. We make use of mild acidification protocols to fabricate hybrid gels using calcium alginate in the presence of a preformed thermally triggered gel based on a low-molecular-weight gelator (LMWG) 1,3:2:4-di(4-acylhydrazide)-benzylidene sorbitol (DBS-CONHNH ). Nonwater-soluble calcium carbonate slowly releases calcium ions over time when exposed to an acidic pH, triggering the assembly of the calcium alginate gel network. We combined the gelators in different ways: (i) the LMWG was used as a template to spatially control slow calcium alginate gelation within preformed gel beads, using glucono-δ-lactone (GdL) to lower the pH; (ii) the LMWG was used as a template to spatially control slow calcium alginate gelation within preformed gel trays, using diphenyliodonium nitrate (DPIN) as a photoacid to lower the pH, and spatial resolution was achieved by masking. The dual-network hybrid gels display highly tunable properties, and the beads are compatible with stem cell growth. Furthermore, they preserve the LMWG function of inducing in situ silver nanoparticle (AgNP) formation, which provides the gels with antibacterial activity. These gels have potential for eventual regenerative medicine applications in (e.g.) bone tissue engineering.