Mechanotyping of Organoids for Assessing Drug‐Induced Injuries

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.

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Publication Details

Journal
Advanced Materials
Published
2025-11-05
DOI
https://doi.org/10.1002/adma.202509675
Primary Topic
Cellular Mechanics and Interactions
Type
article
Field-Weighted Citation Impact
0.00

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article

Mechanotyping of Organoids for Assessing Drug‐Induced Injuries

Daryush D. Mehta, Alexander Alexeev, Orhun K. Muratoglu, Maksymilian Prondzynski et al.
Advanced Materials
Cellular Mechanics and Interactions
article

Mechanotyping of Organoids for Assessing Drug‐Induced Injuries

Daryush D. Mehta, Alexander Alexeev, Orhun K. Muratoglu, Maksymilian Prondzynski, Hamzeh Ghasemzadeh, Amir Poorghani, Murat Kaynak, Yashasvi Tharani, O. Berk Usta, Martin L. Yarmush, Matilda Holtz, William T. Pu, Mehmet Aşık, Elif E. Inan
article en

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.

Advanced MaterialsVol. 38(5)
Rutgers, The State University of New Jersey (US), University of Central Florida (US), Boston Medical Center (US), Boston Children's Hospital (US), Georgia Institute of Technology (US), Shriners Hospitals for Children - Erie (US), Harvard University (US), MGH Institute of Health Professions (US), Massachusetts General Hospital (US), Environmental and Occupational Health Sciences Institute (US), Shriners Hospitals for Children - Boston (US), Harvard Stem Cell Institute (US)
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, Division of Electrical, Communications and Cyber Systems
Openalex Percentile: Top 66%
Cellular Mechanics and Interactions
DOIOpen Access PDFOpenAlex
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