Organoids and organs-on-chips (OoCs) have emerged as powerful tools to replicate human tissues in the lab, but recreating the body’s complex mechanical environment remains a major challenge. A new review led by researchers from Nanjing University of Chinese Medicine, Nanjing University of Posts and Telecommunications, and Nanjing University of Information Science and Technology systematically addresses this gap, highlighting how mechanical cues are fundamental to building functional, lifelike models.
Published in Nano Research on June 8, the review “Mechanical force in organoid and organ-on-a-chip systems: Design principles, biological effects, and translational applications” provides a comprehensive overview of how cells sense and respond to physical signals such as pressure, shear stress, adhesion, and contractility. The authors argue that faithfully replicating these forces is as critical as biochemical factors for achieving physiological relevance.
“Cells are constantly exposed to mechanical stimuli in the body—heartbeat, blood flow, breathing, even the stiffness of surrounding tissue. If we ignore these forces in our lab models, we miss a key part of how organs actually work,” explained corresponding author Dr. Yang Zhang, Professor at Nanjing University of Chinese Medicine.
The review traces the evolution of culture methods from simple static scaffolds to advanced dynamic systems like microfluidics, bioprinting, and magnetic levitation. It shows how each technique applies distinct mechanical forces to guide cell self-organization and maturation. For example, microfluidic chips can simulate blood flow shear stress, while flexible membranes recreate the rhythmic stretching of lungs or the peristalsis of intestines.
A major focus is on organ-specific OoC models. In lung-on-a-chip devices, cyclic strain mimics breathing and helps maintain the alveolar-capillary barrier. Heart-on-a-chip platforms combine mechanical stretching with electrical pacing to mature cardiomyocytes. Tumor-on-a-chip systems replicate the stiff matrix and high interstitial pressure of cancerous tissues, revealing how mechanics drive invasion and drug resistance. Kidney, liver, and gut models similarly rely on controlled fluid flow and pressure to maintain tissue-specific functions.
“Each organ has its own mechanical signature. By engineering those signatures into chips, we can study diseases and test drugs in ways that animal models or static cultures cannot achieve,” said co-corresponding author Dr. Wei Wang, Professor at Nanjing University of Posts and Telecommunications.
Despite significant progress, the review identifies persistent challenges: integrating multiple mechanical signals across scales, ensuring long-term stability of stimulation, and developing materials that can dynamically adapt like native extracellular matrix. The authors also highlight the need for standardized protocols and multi-organ coupling to study systemic diseases.
Looking forward, the team envisions a new generation of “mechano-intelligent” systems. “We are moving toward closed-loop platforms where sensors monitor mechanical conditions in real time and adjust them automatically—like a smart incubator for organoids. Combined with AI and advanced biomaterials, these tools could one day serve as ‘digital twins’ of human organs for precision medicine.”
The review underscores the indispensable role of mechanical engineering in advancing organoid and OoC technologies. As the field matures, it promises to unlock deeper understanding of development, disease, and regeneration—all guided by the hidden hand of mechanical force.
This work was supported by the National Natural Science Foundation of China (Grant Nos. 82302847 and 62205157).
Journal: Nano Research
DOI: 10.26599/NR.2026.94908549
Article Title: Mechanical forces: The hidden conductor shaping organoids and organs-on-chips
Publication Date: June 8, 2026
Publisher: Tsinghua University Press
Funding: National Natural Science Foundation of China
Source: EurekAlert