Bidirectional Mechanical Stimulation Enables Biomechanical Coupling and Functional Maturation in Arterial...

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Cardiovascular Research

Background:

• Engineering functional arterial tissues requires mimicking native mechanical environments.
• Existing methods often lack the dynamic cues necessary for complete tissue maturation.
• Arterial microphysiological systems (aMPSs) are crucial for studying vascular function and disease.

Purpose of the Study:

• To introduce and validate a bidirectional stimulation approach (blood and tissue side stretch - BTS) for arterial tissue engineering.
• To assess the efficacy of BTS in promoting the maturation of arterial microphysiological systems (aMPSs).
• To develop a more physiologically relevant platform for vascular tissue engineering and disease modeling.

Main Methods:

• Co-culture of human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) in a bilayered vessel structure.
• Application of cyclic circumferential stretch (BTS) to mimic in vivo biomechanical forces.
• Assessment of tissue architecture, cellular behavior, barrier function, and vasomotor responsiveness.

Main Results:

• BTS stimulation enhanced collagen fiber alignment and smooth muscle cell (SMC) contractile marker expression.
• Improved barrier function and junctional protein localization were observed in HUVECs.
• The matured aMPS demonstrated vasomotor responsiveness and biomechanical integrity, outperforming static controls.

Conclusions:

• The BTS approach effectively recapitulates key in vivo biomechanical cues for vascular tissue engineering.
• This method significantly advances the maturation of arterial microphysiological systems (aMPSs).
• The developed platform offers a scalable, biomimetic solution for vascular research, drug testing, and regenerative medicine.