Bioprinted microvasculature: progressing from structure to function.

Area of Science:

• Biotechnology
• Regenerative Medicine
• Tissue Engineering

Background:

• Efficient *in vitro* microvascularization is crucial for generating complex tissue constructs via 3D bioprinting.
• Microvasculature fabrication is challenging due to its hollow lumen, branched topology, and complex signaling environment.
• Existing techniques address only parts of the microvascularization challenge, failing to recreate all essential characteristics simultaneously.

Purpose of the Study:

• To present a novel three-part framework for generating mature microvascular constructs by integrating existing techniques.
• To highlight extrusion-based 3D bioprinting as a central technology for engineering hierarchical microvasculature.
• To address critical needs in tissue engineering and advance regenerative medicine and *ex vivo* human tissue modeling.

Main Methods:

• Extrusion-based 3D bioprinting to create a mesoscale foundation of hollow, endothelialized channels.
• Utilizing biochemical and biophysical cues to stimulate endothelial sprouting and form capillary-mimetic networks.
• Construct conditioning to promote enhanced network maturity.

Main Results:

• The proposed framework integrates multiple techniques to overcome microvascularization challenges.
• Extrusion-based bioprinting is identified as a key technology for creating hierarchical microvascular structures.
• The integrated approach facilitates the generation of more mature and functional microvascular networks.

Conclusions:

• Successful biofabrication of functionally engineered microvasculature is achievable through the proposed integrated framework.
• This approach holds significant potential for advancing regenerative medicine and *ex vivo* human tissue modeling.
• The framework provides a pathway to overcome current limitations in 3D bioprinting for vascularized tissue generation.