Controlled dissolution of freeform 3D printed carbohydrate glass scaffolds in hydrogels using a hydrophobic spray coating.

Freeform 3D printing combined with sacrificial molding promises to lead advances in production of highly complex tubular systems for biomedical applications. Here we leverage a purpose-built isomalt 3D printer to generate complex channel geometries in hydrogels which would be inaccessible with other techniques. To control the dissolution of the scaffold, we propose an enabling technology consisting of an automated nebulizer coating system which applies octadecane to isomalt scaffolds. Octadecane, a saturated hydrocarbon, protects the rigid mold from dissolution and provides ample time for gels to set around the sacrificial structure. With a simplified model of the nebulizer system, the robotic motion was optimized for uniform coating. Using a combination of stimulated Raman scattering (SRS) microscopy and X-ray computed tomography, the coating was characterized to assess surface roughness and consistency. Colorimetric measurements of dissolution rates allowed optimization of sprayer parameters, yielding a decrease in dissolution rates by at least 4 orders of magnitude. High fidelity channels are ensured by surfactant treatment of the coating, which prevents bubbles from clinging to the surface. Spontaneous Raman scattering microspectroscopy and white light microscopy indicate cleared channels are free of octadecane following gentle flushing. The capabilities of the workflow are highlighted with several complex channel architectures including helices, blind channels, and multiple independent channels within polyacrylamide hydrogels of varying stiffnesses.