Human-on-Leaf-Chip: A Biomimetic Vascular System Integrated with Chamber-Specific Organs

Area of Science:

• Biomaterials Science
• Vascular Engineering
• Organ-on-a-Chip Technology

Background:

• Vascular networks are crucial for 3D organ-on-a-chip models, enabling control over physiological variables.
• Existing models often lack the biomimetic complexity of natural vascular systems.
• Developing integrated vascular systems is key for advanced in vitro organ modeling.

Purpose of the Study:

• To fabricate a biomimetic vascular system integrated with chambers for vascularized organ development.
• To create a human-on-leaf-chip system capable of mimicking in vivo cardiovascular architecture.
• To validate the chip's utility for comparative organ-specific metastasis studies.

Main Methods:

• A fabrication strategy inspired by leaf venation and circulatory systems was employed.
• A human-on-leaf-chip system with multiscale biomimetic vasculature was constructed.
• Co-culture of human hepatoma G2 cells (HepG2s), mesenchymal stem cells (MSCs), and human umbilical vein endothelial cells (HUVECs) was performed.

Main Results:

• Successful formation of vasculature and co-culture of multiple cell types within the chip.
• Simulation of organ-specific metastasis revealed distinct cancer cell encapsulation by MSCs, but not HepG2s.
• The system demonstrated feasibility for comparative metastasis studies in a single chip.

Conclusions:

• The bioinspired human-on-leaf-chip effectively mimics complex cardiovascular architecture and supports vascularized organ development.
• The chip is suitable for comparative organ-specific metastasis studies, highlighting differences in cancer cell interactions.
• This platform offers flexibility for modification and holds significant potential for studying organ-to-organ crosstalk and disease progression.