2. Academic Validation
  3. 3D bioprinted human-scale intestine models for physiological and microbial insights through fluid-driven heterogeneity

3D bioprinted human-scale intestine models for physiological and microbial insights through fluid-driven heterogeneity

  • Sci Adv. 2025 Nov 21;11(47):eady6562. doi: 10.1126/sciadv.ady6562.
Ziqi Gao 1 2,  Huilong Du 1 2,  Shuyuan Yu 1 2,  Qi Li 3,  Ruiqi Shi 4,  Zengliang Jiang 5,  Huayong Yang 1 2,  Luqi Shen 4,  Hongzhao Zhou 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou 310058, People's Republic of China.
  • 2 School of Mechanical Engineering, Zhejiang University, Hangzhou 310058, People's Republic of China.
  • 3 School of Engineering, Hangzhou Normal University, Hangzhou 311121, People's Republic of China.
  • 4 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, People's Republic of China.
  • 5 College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro Food Processing, Fuli Institute of Food Science, Zhejiang University, Zhejiang 310058, People's Republic of China.
PMID: 41270182 DOI: 10.1126/sciadv.ady6562
Abstract

The small intestine's intricate structure enables vital functions such as nutrient absorption, microbial defense, and barrier protection, yet replicating its complexity in vitro remains a substantial challenge. We engineered a three-dimensional bioprinted intestinal model featuring biomimetic circular folds and zonated shear stress distribution to recapitulate native physiology. A filament-resolved embedded bioprinting approach enabled high-fidelity fabrication of thin-walled, continuous structures that shaped physiologically relevant flow microenvironments essential for epithelial development. These shear stress patterns regulated tight junctions, secretory activity, and transporter expression, driving region-specific epithelial specialization into barrier or absorptive phenotypes. Coculture with probiotic Lactobacillus plantarum activated localized immune responses and modulated epithelial function through spatially distinct colonization. Regional flow differences governed the transport of nutrient and drug probes via transcellular and paracellular pathways. Quantitative assessment of drug absorption demonstrated strong in vitro-in vivo correlation, validating physiological relevance. By unifying structural, mechanical, and functional complexity, this platform advances intestinal models for studying physiology, host-microbe interactions, and drug transport.

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