A "Nonsolvent Quenching" Strategy for 3D Printing of Polysaccharide Scaffolds with Immunoregulatory Accuracy.

3D printing enables the customized design of implant structures for accurately regulating host responses. However, polysaccharides, as a major biomaterial category with versatile immune activities, are typically "non-printable" due to the collapse of their filaments extruded during printing. This challenge renders their potential as immunomodulatory scaffolds underexploited. Here, inspired by the quench hardening in metal processing, a nonsolvent quenching (NSQ) strategy is innovatively designed for the 3D printing of polysaccharides. Through rapid solvent exchanging, NSQ instantly induces surface hardening to strengthen the polysaccharide filaments upon extrusion, requiring neither chemical modification nor physical blending that alters the material properties. Tested with five polysaccharides with varying physicochemical properties, NSQ prints predesigned structures at organ-relevant scales and a long shelf-life over 3 months. Glucomannan scaffolds, fabricated via NSQ with different grid spacings (1.5 and 2.5 cm), induce distinct host responses upon murine subcutaneous implantation-from specific carbohydrate receptor activation to differential immunocytes accumulation and tissue matrix remodeling-as mechanistically validated in wild-type and Tlr2 knockout mice. Overall, NSQ as a facile and generic strategy is demonstrated to fabricate polysaccharide scaffolds with improved shape fidelity, thereby potentially unmasking their accurate immunomodulatory activities for future biomaterials design.