Ionic crosslinking strategies for poly(acrylamide) /alginate hybrid hydrogels

Ionically crosslinked alginate hydrogels have been widely studied for application in tissue engineering. Crosslinking of alginates is routinely done by ionic interaction of the carboxyl groups with multivalent anions such as Ca2+ and Fe3+. In more complex hydrogel designs, such as interpenetrating network hydrogels and double network hydrogels, alginates have been combined with other synthetic polymers to benefit from the advantages of both worlds. The effect of different ions on the properties of single network alginate hydrogels and double network poly(acrylamide)/alginate hydrogels have been studied extensively. However, past reports offer less in terms of comparing different crosslinking methods or different salt precursors. Here, we explore the influence of ionic crosslinking strategies used for crosslinking alginate in double network P(AAm)/Alginate hybrid hydrogels. A comparison is made between different calcium-based crosslinking methods, including a two-step method using CaCl2, a one-step method using CaSO4, and a one-step method using the combination of CaCO3 with glucono-δ-lactone (GDL). Furthermore, the effect of different metal ions is investigated, including Fe3+, Al3+, Ba2+, Sr2+, and Ca2+. Mechanical properties of the resulting gels are analyzed by tensile and compression testing, revealing a strong correlation between preparation protocol, counter-ion identity, and mechanical response.