Year: 2025
Type: article
Abstract: Changes in the mechanical properties, i.e., mechanotypes, of tissues are powerful indicators of disease states and drug-induced injuries. Although differential mechanotyping has emerged as a valuable tool for non-invasive disease diagnostics, it remains particularly underutilized for drug safety and efficacy screening in preclinical studies. This is largely due to the lack of scalable mechanotyping methods compatible with modern 3D organoid models. Here, the Centrifugal Mechanical Testing (CeMeT) platform is presented, which enables rapid, robust, and label-free mechanotyping of 3D organoids. Utilizing centrifugal mechanical principles and high-speed imaging, this platform achieves high accuracy and precision and can assess a wide range of tissue stiffness. It is demonstrated that the CeMeT platform distinguishes mechanical properties, i.e., stiffness and elastic recovery, among various hydrogel bead formulations and hiPSC-derived cardiac organoids, successfully detecting pathological changes in mechanotype with high sensitivity. Through experiments on organoids treated with drugs like pergolide and Cytochalasin-D, it is established that changes in organoid mechanotypes can serve as reliable indicators of drug-induced tissue injuries in vitro. These findings position the CeMeT platform as a potentially transformative tool for early-stage drug safety assessment through mechanotyping, with immediate applications extending to fundamental disease pathology research and drug efficacy testing using organoid models.
Source: Advanced Materials
Institutions: Harvard University, Massachusetts General Hospital, Shriners Hospitals for Children - Boston, Boston Children's Hospital, University of Central Florida, Georgia Institute of Technology, MGH Institute of Health Professions, Harvard Stem Cell Institute, Rutgers, The State University of New Jersey
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: bronze
Funders: National Science Foundation, Harvard University, Shriners Hospitals for Children, Voice Health Institute, Additional Ventures, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Electrical, Communications and Cyber Systems
Awards: NNCI: Center for Nanoscale Systems (CNS), G2347808973, G4055141715, G4671203234, Early Toxicity Detection Technologies via Exosomal Signatures in 3D Hepatic Tissues, G6192545370, Deep Supercooling of Liver Cells and 2D and 3D Tissue Constructs: Effect of Attachment, Deep Supercooling of Red Blood Cells: Towards Practical Long Term Storage, NSF Engineering Research Center for Advanced Technologies for Preservation of Biological Systems (ATP-Bio), G9000111257, G9000180642, G9000214294, G9000339481, On Demand Dissoluble Supramolecular Hydrogels: Towards Pain Free Burn Dressings
OpenAlex ID: W4415923677