Machine Learning-Based Prediction of Bioprinting Quality Using Integrated Experimental and Computational Data

Three-dimensional (3D) bioprinting of hydrogel inks is an enabling technology for tissue engineering and the fabrication of personalized drug-delivery systems. However, in most laboratories the extrusion parameters are still optimized by slow, resource-intensive trial-and-error, because printability depends on the combined and often nonlinear influence of ink composition, extrusion pressure, and nozzle geometry rather than on any single variable. Alginate–methylcellulose (Alg–MC) is a widely used pharmaceutical bioink whose shear-thinning behavior makes this optimization particularly demanding. Here we developed a physics-informed machine-learning framework that predicts extrusion print quality before printing. A hybrid dataset of 3280 labeled samples was assembled by combining laboratory extrusion experiments, computational fluid dynamics (CFD) simulations of nozzle flow, and controlled augmentation with a deep belief network (DBN). Five physics-informed features encoding pressure-to-diameter and shear-rate interactions were engineered to embed rheological domain knowledge. Five base classifiers alongside two ensemble strategies, seven models in all, were benchmarked under five-fold stratified cross-validation. The voting ensemble performed best (accuracy, 93.3%; F1 = 0.929), narrowly ahead of the stacking ensemble (93.3% accuracy; F1 = 0.928). Alg:MC ratio, extrusion pressure, and the pressure–diameter interaction term stood out as the dominant predictors, consistent with established alginate rheology. On external validation—withholding one composition ratio and one needle gauge entirely from training and testing on those genuinely unseen conditions—accuracy was 75.9%, a stricter test than a random held-out split. Overall, the framework offers a practical, interpretable way to cut down experimental burden in pharmaceutical bioink development.