Democratizing Organ-On-Chip Technologies With a Modular, Reusable, and Perfusion-Ready Microphysiological System

Area of Science:

• Biotechnology
• Tissue Engineering
• Microfluidics

Background:

• Organ-on-chip (OOC) and microphysiological systems (MPS) offer dynamic cell culture but face adoption barriers due to complex fabrication, material limitations (e.g., polydimethylsiloxane), and poor modularity.
• Existing static cell culture methods lack the physiological relevance of dynamic microenvironments crucial for advanced in vitro modeling.
• Widespread use of OOC/MPS is limited by fabrication complexity, material constraints, and lack of modularity, hindering broader scientific adoption.

Purpose of the Study:

• To present a novel, modular microphysiological system (MPS) platform designed for ease of use, enhanced reproducibility, and broad applicability in organ-on-chip development.
• To decouple model establishment from perfusion experiments, streamlining workflows for researchers.
• To establish a generalizable framework for modular tissue-chip development adaptable to diverse organ systems.

Main Methods:

• Development of a modular MPS platform using layered elastomeric inserts for dual monolayer cell culture within a reusable acrylic cassette for perfusion.
• Validation using dual epithelial and endothelial cell co-culture under static and perfused conditions, including shear stress application.
• Utilizing vinyl cutting for reproducible manufacturing and material testing for biocompatibility assessment.

Main Results:

• The platform demonstrated high manufacturing fidelity and biocompatibility, supporting long-term cell culture (up to 14 days).
• Successful co-culture of epithelial and endothelial cells was achieved, with observed shear-induced alignment of HUVECs under perfusion.
• The modular design facilitated uniform cell seeding, imaging access, and parallelized experimentation with minimized pump usage.

Conclusions:

• The developed modular MPS platform overcomes key limitations of current OOC technologies, offering a user-friendly, reproducible, and versatile solution.
• This approach democratizes advanced in vitro model systems, making them accessible to labs lacking specialized microfabrication infrastructure.
• The platform serves as a foundational framework for developing diverse organ-specific tissue chips, advancing in vitro research.