Nanopatterned Cell Sheet Assembly of Biomimetic Cardiac Laminae for Modeling Structure-Function Relationships

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cardiovascular Research

Background:

• Replicating native human myocardium's 3D structure and function is a key challenge in cardiac tissue engineering.
• Existing methods often struggle to achieve the complex architecture and coordinated function of native heart tissue.

Purpose of the Study:

• To develop a scaffold-free strategy for fabricating multilayered human cardiac tissues with tunable structural anisotropy and helical alignment.
• To create a modular, bottom-up platform for engineering functional anisotropic cardiac tissues.

Main Methods:

• Utilized biomimetic nanotopographical patterning and a thermoresponsive polymer interface to generate aligned cardiac cell sheets.
• Employed a coculture system with human induced pluripotent stem cell-derived endocardial-like endothelial cells for robust sheet formation and release.
• Engineered 4-layered laminae by stacking cardiac sheets with defined angular offsets to mimic ventricular wall fiber orientation.

Main Results:

• Demonstrated successful detachment and transfer of intact aligned cardiac cell sheets.
• Identified coculture with specific endothelial cells as crucial for extracellular matrix deposition and tissue integrity.
• Engineered helically aligned cardiac tissues exhibiting enhanced contractile synchrony and superior contractile function compared to controls.

Conclusions:

• Introduced a novel scaffold-free platform for constructing functionally anisotropic cardiac tissues.
• The developed tissues mimic native myocardial architecture, offering improved contractile properties.
• This platform provides new tools for studying myocardial biomechanics, cardiac development, disease, and regenerative therapies.