3D printed chip as platform to vascularize hiPSCs-derived kidney organoids.

Area of Science:

• Regenerative Medicine
• Biomaterials Engineering
• Developmental Biology

Background:

• Human induced pluripotent stem cells (hiPSCs)-derived kidney organoids mimic early kidney development but suffer from poor vascularization, limiting their maturation and utility.
• Limited vascularization restricts oxygen and nutrient diffusion, hindering differentiation and complex tissue formation in kidney organoids.
• Existing vascularization strategies, such as organ-on-chip systems and co-cultures, have limitations in efficiency and scalability.

Purpose of the Study:

• To develop an automated, cost-effective, and efficient method for vascularizing kidney organoids using a 3D printed chip.
• To investigate the formation of capillary-like structures within kidney organoids cultured in a novel 3D printed microfluidic device.
• To enhance the potential of kidney organoids for applications in drug testing and disease modeling through improved vascularization.

Main Methods:

• Fabrication of a custom 3D printed chip with sacrificial pluronic material to create perfusable channels and central gel compartments.
• Seeding of human umbilical vein endothelial cells (HUVECs) within the 3D printed chip, followed by the introduction of kidney organoids embedded in a decellularized extracellular matrix (ddECM) hydrogel.
• Co-culture of kidney organoids and HUVECs under perfusion for five days to promote vascular network formation.

Main Results:

• The 3D printed chip successfully facilitated the formation of capillary-like structures extending towards the kidney organoids.
• Vascularization was observed in both outer and central regions of the organoids, co-localizing with kidney-specific markers (LTL and PODXL).
• The developed strategy enabled the formation of primitive capillary networks throughout the kidney organoids, overcoming previous limitations.

Conclusions:

• A novel 3D printed chip effectively promotes vascularization in hiPSC-derived kidney organoids, enhancing their developmental potential.
• This approach offers a promising platform for improving organoid maturation, enabling more accurate drug screening and disease modeling.
• The automated and cost-effective nature of the 3D printing technique makes it suitable for broader research applications in kidney organoid development.