Large-scale perfused tissues via synthetic 3D soft microfluidics.

Area of Science:

• Regenerative Medicine
• Biomaterials Engineering
• Tissue Engineering

Background:

• Vascularization is a critical challenge for engineering large-scale tissues and organoids.
• Existing methods struggle to create dense, small-scale vessel networks needed for tissue perfusion.
• Hypoxia and necrosis limit the viability of large engineered tissues.

Purpose of the Study:

• To develop a novel strategy for perfusing large engineered tissues using synthetic capillary-scale vessels.
• To overcome limitations in current vascularization techniques for regenerative medicine.
• To create a versatile platform for generating complex, viable engineered human tissues.

Main Methods:

• Utilized a 3D-printable, 2-photon-polymerizable hydrogel formulation for soft microfluidics.
• Fabricated precise microvessel networks at scales below the diffusion limit.
• Cultured large-scale engineered tissues in vitro, assessing viability, proliferation, and morphogenesis.

Main Results:

• Achieved successful perfusion of multi-mm³ tissue constructs with synthetic capillary-scale vessels.
• Demonstrated long-term viability, proliferation, and complex morphogenesis in engineered tissues without hypoxia or necrosis.
• Showed accelerated neural differentiation in perfused neural constructs via scRNAseq and immunohistochemistry.
• Illustrated platform versatility with perfusion of developing neural and liver tissues.

Conclusions:

• The developed 3D soft microfluidic platform enables synthetic vascularization of large engineered tissues.
• This approach overcomes critical limitations in regenerative medicine, allowing for unprecedented scale and complexity.
• The platform supports long-term tissue viability and function, accelerating differentiation and opening doors for advanced tissue models.