The Influence of Crosslinking Agents on the Matrix Properties of Hydrogel Structures Based on Sodium Alginate

A comparative study of gelation processes in aqueous solutions of sodium alginate initiated by their chemical crosslinking with divalent Ca²⁺ or Ba²⁺ ions is carried out. 3D cryoprinted hydrogel scaffolds with certain architectonics are formed from the studied compositions containing various concentrations of crosslinking agents. It is shown that increasing the concentration of the crosslinking agent from 2 up to 10 wt % leads to the improvement in the strength characteristics of alginate structures. Here, scaffolds crosslinked with 10% aqueous solutions of both CaCl₂ and BaCl₂ retain their structural stability during 21 days of incubation in a culture medium at 37°C. It is found during in vitro experiments on cultures of multipotent mesenchymal stromal cells derived from rat adipose tissue that samples crosslinked with Ba²⁺ ions demonstrate a moderate cytotoxic effect and manifest their inability to maintain cell adhesion as opposed to nontoxic scaffolds crosslinked in aqueous solutions of CaCl₂. In vivo analysis of experimental samples on an intramuscular implantation model for male Wistar rats also confirms moderate cytotoxicity of the alginate scaffolds formed using Ba²⁺ ions as crosslinking agents. The results obtained make it possible to assert that sodium alginate crosslinked with a 10% aqueous solution of CaCl₂ can be considered the most promising for various biomedical applications among all the materials studied by us.