Influence of ionic crosslinkers (Ca2+/Ba2+/Zn2+) on the mechanical and biological properties of 3D Bioplotted Hydrogel Scaffolds

Three dimensional (3D) bioplotting requires appropriate crosslinkers to crosslink the hydrogel precursor while simultaneously maintaining the viability of embedded cells. However, the evaluation and comparison of various types of crosslinkers in bioplotting remains underexplored to date. This paper presents our study of the influence of three ionic crosslinkers—calcium chloride (CaCl₂), barium chloride (BaCl₂), and zinc chloride (ZnCl₂)—on the mechanical and biological properties of 3D bioplotted alginate scaffolds. The scaffold mechanical properties characterized included the elastic modulus, swelling, and degradation while the biological properties considered included Schwann cell viability and surface morphology. The mechanical and biological properties of the bioplotted scaffolds were both dependent on the crosslinkers used for fabrication; specifically, crosslinking ions resulted in the elastic modulus of the hydrogels decreasing in the order BaCl₂>CaCl₂>ZnCl₂ over 42 days while Schwann cell viability decreased in the order CaCl₂>BaCl₂>ZnCl₂ over 7 days. Taken together, these results offer insights that are effective in terms of manipulating the 3D bioplotting process so as to tune and optimize the mechanical and biological performance of the plotted scaffolds for tissue engineering applications.