Depletion Flocculation of High Internal Phase Pickering Emulsion Inks: A Colloidal Engineering Approach to Develop 3D Printed Porous Scaffolds with Tunable Bioactive Delivery

Flocculation is a type of aggregation where the surfaces of approaching droplets are still at distances no closer than a few nanometers while still remaining in close proximity. In a high internal-phase oil-in-water (O/W) emulsion, the state of flocculation affects the bulk flow behavior and viscoelasticity, which can consequently control the three-dimensional (3D)-printing process and printing performance. Herein, we present the assembly of O/W Pickering high-internal-phase emulsions (Pickering-HIPEs) as printing inks and demonstrate how depletion flocculation in such Pickering-HIPE inks can be used as a facile colloidal engineering approach to tailor a porous 3D structure suitable for drug delivery. Pickering-HIPEs were prepared using different levels of cellulose nanocrystals (CNCs), co-stabilized using "raw" submicrometer-sized sustainable particles from a biomass-processing byproduct. In the presence of this sustainable particle, the higher CNC contents facilitated particle-induced depletion flocculation, which led to the formation of a mechanically robust gel-like ink system. Nonetheless, the presence of adsorbed particles on the surface of droplets ensured their stability against coalescence, even in such a highly aggregated system. The gel structures resulting from the depletion phenomenon enabled the creation of high-performance printed objects with tunable porosity, which can be precisely controlled at two distinct levels: first, by introducing voids within the internal structure of filaments, and second, by generating cavities (pore structures) through the elimination of the water phase. In addition to printing efficacy, the HIPEs could be applied for curcumin delivery, and in vitro release kinetics demonstrated that the porous 3D scaffolds engineered for the first time using depletion-flocculated HIPE inks played an important role in 3D scaffold disintegration and curcumin release. Thus, this study offers a unique colloidal engineering approach of using depletion flocculation to template 3D printing of sustainable inks to generate next-generation porous scaffolds for personalized drug deliveries.