Organ-on-a-Chip: A Roadmap for Translational Research in Human and Veterinary Medicine

Abstract

In this review we offer a guide to organ-on-chip (OoC) technologies, covering the full experimental pipeline, from organoid derivation and culture, through microfluidic device fabrication and design strategies, to perfusion systems and data acquisition with AI-assisted analysis. At each stage, we highlight both the advantages and limitations, providing a balanced perspective that aids experimental planning and decision-making. By integrating insights from stem cell biology, bioengineering, and computational analytics, this review presents a compilation of the state of the art of OoC research. It emphasizes practical considerations for experimental design, reproducibility, and functional readouts while also exploring applications in human and veterinary medicine. Furthermore, key technical challenges, standardization issues, and regulatory considerations are discussed, offering readers a clear roadmap for advancing both foundational studies and translational applications of OoC systems.

Keywords: microfluidics; organ-on-chip; organoids; translational medicine; veterinary models.

Figure 1

Publication output of organ-on-chip, single-organ chips, and multi-organ chips in past 15 years. (Data represent number of PubMed-indexed publications retrieved using queries ‘Organ-on-chip’, ‘Single-Organ Chips’, and ‘Multi-Organ Chips’).

Figure 2

The fabrication of organ-on-chip (OoC) devices. Molding is achieved using methods such as 3D printing, photolithography, micro-milling, or laser ablation. Once the mold is prepared, channels are cast in PDMS or thermoplastics. For proof-of-concept studies, soft lithography is commonly used, while hot embossing and injection molding are preferred for large-scale production. To create closed microchannels, the patterned layer is bonded to PDMS, thermoplastic, or glass substrates using techniques such as oxygen plasma treatment, the use of double-sided adhesives, thermal or chemical bonding, laser welding, or ultrasonic welding. Hydrogels are integrated into the chip and patterned to define channels and chambers. Several micropatterning strategies can be applied, including micromolding, pillar/phaseguide structuring, plasma treatment, laser ablation, 3D printing or bioprinting, photolithography, and xurography. Created with BioRender.com.

Figure 3

Biosensors can be integrated directly into OoC systems, or the chip can be designed to be compatible with standard laboratory equipment. Common sensor types include mechanical sensors (for measuring shear stress, tissue deformation, and cell contractility), electrochemical sensors (for monitoring pH, oxygen, glucose, and other metabolites), and optical sensors (for detecting absorbance, fluorescence, scattering, and refractive index changes). The large and complex datasets generated by these biosensors can be further analyzed using artificial intelligence (AI) tools.