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Updated: Dec 7, 2025
Micropatterning and Assembly of 3D Microvessels
Published on: September 9, 2016
Direct extrusion of individually encapsulated endothelial and smooth muscle cells mimicking blood vessel structures
E Bosch-Rué1, Luis M Delgado1, F Javier Gil1
1Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, Spain.
Insights
Researchers developed tissue-engineered blood vessels (TEBVs) using alginate and collagen hydrogels. This novel method ensures high cell viability and natural cell alignment, offering a promising alternative for cardiovascular disease treatment.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Cardiovascular Research
Background:
- Cardiovascular diseases (CVDs) are the leading cause of global mortality, with atherosclerosis being a primary contributor.
- Current treatments like autologous bypass surgery have limitations, necessitating alternative solutions.
- Tissue-engineered blood vessels (TEBVs) offer a promising alternative for vascular replacement, aiming to replicate native vessel architecture and function.
Purpose of the Study:
- To develop a novel method for creating bilayered tissue-engineered blood vessels (TEBVs).
- To mimic the native blood vessel structure with specific cell types and their physiological alignment.
- To assess cell viability, proliferation, and alignment within the engineered constructs.
Main Methods:
- Utilized a triple coaxial nozzle to extrude alginate and collagen hydrogels encapsulating human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs).
- Incorporated a sacrificial polymer for controlled formation of bilayered hollow fibers upon contact with a crosslinking solution.
- Controlled TEBV size via injection speed and assessed construct robustness and liquid perfusion capabilities.
Main Results:
- Successfully fabricated robust, bilayered hollow fibers mimicking native blood vessel architecture.
- Achieved high cell viability (over 90%) for both HUVECs and HASMCs post-extrusion and during 20 days of culture.
- Demonstrated significant alignment of HASMCs perpendicular and HUVECs parallel to the TEBV axis, resembling *in vivo* physiological arrangement.
Conclusions:
- The proposed extrusion technique enables rapid fabrication of TEBV-like structures.
- The method supports high vascular cell viability, proliferation, and natural cellular alignment.
- This approach presents a viable strategy for developing functional TEBVs as alternatives to traditional treatments for cardiovascular diseases.
Abstract:
Cardiovascular diseases (CVDs) are considered the principal cause of worldwide death, being atherosclerosis the main etiology. Up to now, the predominant treatment for CVDs has been bypass surgery from autologous source. However, due to previous harvest or the type of disease, this is not always an option. For this reason, tissue engineered blood vessels (TEBV) emerged as an alternative graft source for blood vessel replacement. In order to develop a TEBV, it should mimic the architecture of a native blood vessel encapsulating the specific vascular cells in their respective layers with native alignment, and with appropriate mechanical stability. Here, we propose the extrusion of two different cell encapsulating hydrogels, mainly alginate and collagen, and a sacrificial polymer, through a triple coaxial nozzle, which in contact with a crosslinking solution allows the formation of bilayered hollow fibers, mimicking the architecture of native blood vessels. Prior to extrusion, the innermost cell encapsulating hydrogel was loaded with human umbilical vein endothelial cells (HUVECs), whereas the outer hydrogel was loaded with human aortic smooth muscle cells (HASMCs). The size of the TEVB could be controlled by changing the injection speed, presenting homogeneity between the constructs. The obtained structures were robust, allowing its manipulation as well as the perfusion of liquids. Both cell types presented high rates of survival after the extrusion process as well as after 20 d in culture (over 90%). Additionally, a high percentage of HASMC and HUVEC were aligned perpendicular and parallel to the TEBV, respectively, in their own layers, resembling the physiological arrangement foundin vivo. Our approach enables the rapid formation of TEBV-like structures presenting high cell viability and allowing proliferation and natural alignment of vascular cells.
