Sr2+ vs. Ca2+ as post-processing ionic crosslinkers: implications for 3D bioprinting of polysaccharide hydrogels in tissue engineering

Abstract

Among the possible ionic crosslinkers Ca2+ is the most widely used. However, due to its numerous physiological functions, other cations such as Sr2+ may be more suitable depending on the application. Because a systematic comparison is currently lacking, this work aims to compare solutions of CaCl2 and SrCl2 as ionic crosslinkers of alginate- and cellulose-based materials and to investigate their effects on the structural and biological properties of 3D bioprinted scaffolds. In particular, swelling and degradation under cell culture conditions, mechanical properties (with quasi-static compression tests), surface topology (with scanning electron microscopy and atomic force microscopy) and elemental composition were investigated. In addition, cytotoxicity on pancreatic islet cells was assessed by measuring viability, metabolic activity and morphology. The obtained results show that Sr2+-crosslinked scaffolds have higher compressive strength, swell faster and degrade more slowly under cell culture conditions and have a rougher surface. Both crosslinking agents were gentle on the cells, either when directly embedded into scaffolds or in contact with scaffold extracts, and allowed stable culture for 30 days. However, Sr2+-crosslinked scaffolds elicited higher metabolic activity. Overall, Sr2+ are a viable crosslinking alternative to Ca2+ and allow expanding the range of scaffold properties by adjusting the concentration or ratio in a mixed solution.

Keywords

• 3D printing
• Polysaccharide-based hydrogels
• Crosslinking
• Divalent cations
• Calcium ions
• Strontium ions