The role of multivalent cations in determining the cross-linking affinity of alginate hydrogels: A combined experimental and modeling study

This study explores the development of a comprehensive mathematical model to predict the cross-link density of alginate hydrogels using varying concentrations of divalent and trivalent ions. By systematically investigating the effects of Ca²⁺, Ba²⁺, Cu²⁺, Sr²⁺, Mg²⁺, Fe3⁺ and Al³⁺, the research describes the relationship between ion concentration and cross-link density. Experimental data reveals that the type and concentration of these ions critically influence the mechanical properties of the resulting hydrogels, with trivalent ions such as Fe³⁺ forming stronger, triple cross-links that significantly enhance the hydrogel's mechanical strength. Among the divalent ions, the trend in binding affinity is as follows: Ba²⁺ with the highest affinity followed by Sr²⁺, Ca²⁺ and Cu²⁺, while Mg²⁺ stands out with the lowest affinity, significantly differing from the others. The deviation of Cu²⁺ (transition metal ion) from the expected trend in ion interactions suggests that coordination chemistry, along with ionic radius, valence, and cation coordination abilities, plays a significant role in determining interaction strength with alginate. The proposed model, enhanced with fitting parameters k1 and k2 to account for ion-specific effects, leverages the unique binding affinities and coordination chemistry of each ion to tailor alginate hydrogels for specific applications. The parameter k1 reflects the affinity of the ions for the alginate chains, while k2 captures the coordination abilities and cross-linking efficiency. This work not only advances the understanding of ion-mediated cross-linking in alginate systems but also offers a valuable tool for the design and optimization of hydrogels with precise mechanical properties governed by various applications.