Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues.

Area of Science:

• Biotechnology
• Biomedical Engineering
• Drug Discovery

Background:

• Accurate in vitro modeling of cardiac and skeletal muscle diseases is crucial for therapeutic development.
• Current methods for creating and testing engineered muscle tissues (EMTs) face challenges in reproducibility and require complex instrumentation.
• Existing techniques often suffer from high failure rates and intricate data analysis.

Purpose of the Study:

• To introduce a novel platform and device for the facile and reproducible fabrication and contractility assessment of 3D EMTs.
• To overcome the limitations of existing methods, enabling reliable in vitro disease modeling.
• To facilitate drug discovery workflows by integrating complex bioengineered models.

Main Methods:

• Utilizes a new platform for 3D EMT fabrication from diverse cell sources.
• Employs a label-free, highly-parallel, automation-friendly contractility assay.
• Measures tissue contractility using an instrument capable of simultaneously testing 24 tissues with high sensitivity (micronewton changes).

Main Results:

• Demonstrated reproducible fabrication of functional 3D EMTs capable of twitch and tetanic contractions.
• Successfully measured dose-dependent effects of toxicants on cardiac EMTs, including a cardiotoxic drug (BMS-986094).
• Showcased altered skeletal muscle function in engineered tissues treated with a myosin inhibitor.

Conclusions:

• The developed platform simplifies the integration of advanced engineered tissue models into drug discovery pipelines.
• This approach enhances the reliability and efficiency of in vitro contractility assays for muscle research.
• The technology minimizes the need for specialized training, making complex bioengineered models more accessible to researchers.