Thaw-Induced Gelation of Alginate Hydrogels for Versatile Delivery of Therapeutics

Alginate hydrogels have been extensively used and successfully validated as delivery vehicles of bioactive factors in many tissue engineering applications. This work describes and characterizes a singular alternative method to create alginate hydrogels designated as thaw-induced gelation (TIG). The TIG method involves gelation through the time-dependent release of the polymer or crosslinker by melting into solution. Alginate TIG hydrogels were validated for spatial-temporal control delivery of different cargos including albumin, dextran, and doxorubicin. Chitosan was incorporated into TIG hydrogels to investigate the electrostatic interactions between alginate and the tested cargos. Interestingly, while 90% of doxorubicin was released after 8 h from hydrogels formed with frozen calcium, hydrogels formulated from frozen alginate took 72 h. In addition, the storage modulus of TIG hydrogels prepared from frozen alginate was double that of a hydrogel formed without freezing alginate. Therefore, the utility of TIG strategies are particularly promising for the delivery of therapeutic cargos smaller than the mesh size of the alginate hydrogel, as it enables controlled release of these cargos without any further chemical modifications of the hydrogels. These TIG alginate hydrogels with tunable mechanical properties and control over the delivery of smaller cargos could be useful in many tissue engineering applications.