3D-printed amino acid-restricted foods for special medical purposes to support cancer nutrition therapy

Serine/glycine-free (−SG) diets are recognized for boosting tumor immunotherapy efficacy by remodeling the tumor microenvironment, yet their clinical translation is hindered by aspiration risks and poor patient compliance associated with traditional liquid formulations. To address these challenges, this study leveraged 3D printing to transform −SG nutritional powder into a clinically viable semi-solid formulation. A functional food ink was developed by stabilizing −SG powder in a hydrocolloid matrix formed via electrostatic complexation between cationic chitosan and anionic xanthan gum. Formulation was optimized using response surface design of experiment methodology to maximize printability, with metabolic efficacy and biological safety validated in BALB/c mice, and clinical usability assessed in 20 cancer patients via sensory and direct swallowing tests. Rheological characterization confirmed that the polyelectrolyte network endowed the ink with ideal pseudoplasticity and yield stress—critical for extrusion-based 3D printing. The optimized formulation (1.25% chitosan, 1.25‰ xanthan gum) exhibited exceptional shape fidelity. In vivo studies showed the 3D-printed food for special medical purposes maintained serum serine/glycine depletion without systemic toxicity, supported by stable mouse body weight and normal liver/kidney function. Clinically, the 3D-printed semi-solid formulation significantly enhanced patient compliance, elevating sensory acceptability scores from “like slightly” to “like very much” (32.0 vs. 27.6, p < 0.0001). This study presents a novel application of 3D printing to fabricate texture-modified food for special medical purposes, effectively mitigating aspiration risks associated with traditional liquid amino acid-restricted diets.