Six-axis robotic extrusion of hybrid hydrogels for biomimetic airway model fabrication

Respiratory diseases remain a major global health burden, motivating the need for improved experimental lung models that capture both anatomical geometry and mechanical compliance. Traditional three-axis 3D printers face limitations in replicating the lung's curving, branching structures, often resulting in pore collapse or loss of fidelity. In this study, we demonstrate the use of a six-axis robotic extrusion bioprinter to fabricate anatomically inspired airway structures using hybrid hydrogels composed of Alginate (A) and CarboxyMethyl Cellulose (CMC). By systematically tuning hydrogel formulations, we identified a blend (5% Alginate-7% CMC, i.e., A₅C₇) that provides a balance of viscosity, shear-thinning, and diffusion resistance, resulting in enhanced print fidelity and structural stability compared to single-polymer inks. Using this formulation, the robotic platform successfully printed tubular and bifurcating airway constructs that retained lumen geometry, withstanding axial and diametral compression within ranges relevant to lung tissue mechanics. Printability (Pr ≈ 0.92-1.08) analysis confirmed consistent pore fidelity, while mechanical testing demonstrated elastic recovery under loading. A preliminary aerosol deposition test highlighted the feasibility of coupling these constructs with drug delivery studies, though more sensitive measurement methods will be required. Collectively, this work establishes a proof-of-concept fabrication platform for anatomically accurate and mechanically compliant airway models, which can be adapted in future studies to represent both healthy and pathological respiratory states through targeted modifications in geometry, material composition, and cellular integration.