Orthogonally crosslinked alginate conjugate thermogels with potential for cell encapsulation

Hydrogels with more than one mode of crosslinking have gained interest due to improved control over hydrogel properties such as mechanical strength using multiple stimuli. In this work, sodium alginate was covalently conjugated onto thermoresponsive polyurethanes to prepare hybrid polymers (EPC-Alg) that are responsive to both temperature and Ca2+, forming orthogonally crosslinked hydrogels which are non-toxic to cells. Notably, the crosslinks are fully reversible, allowing for gel strength to be modulated via selective removal of either stimulus, or complete deconstruction of the hydrogel network by removing both stimuli. Higher alginate frac-tions increased the hydrophilicity and Ca2+ response of the EPC-Alg hydrogel, enabling tunable modulation of the thermal stability, stiffness and gelation temperatures. The EPC-Alg hydrogel could sustain protein release for a month and encapsulate neural spheroids with high cell viability after 7-day culture, demonstrating feasibility towards 3D cell encapsulation in cell-based biomedical applications such as cell encapsulation and cell therapy.

Automated summary

Hydrogels with multiple modes of crosslinking, such as the EPC-Alg hydrogel discussed in this study, offer improved control over properties like mechanical strength through the use of multiple stimuli, in this case temperature and Ca2+. These orthogonally crosslinked hydrogels are non-toxic to cells and have fully reversible crosslinks, allowing for modulation of gel strength by selectively removing one or both stimuli. The EPC-Alg hydrogel showed tunable modulation of thermal stability, stiffness, and gelation temperatures, and demonstrated feasibility in cell-based biomedical applications including cell encapsulation and cell therapy.