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Updated: Jun 23, 2025
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Processing of Human Cardiac Tissue Toward Extracellular Matrix Self-assembling Hydrogel for In Vitro and In Vivo Applications
Published on: December 4, 2017
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Engineering a robust and anisotropic cardiac-specific extracellular matrix scaffold for cardiac patch tissue
Te-An Chen1, Brandon B Zhao1, Richard A Balbin1
1Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.
Matrix Biology Plus
|June 17, 2024
Summary
This study optimized human induced pluripotent stem cells-derived cardiac fibroblast extracellular matrix (ECM) production for cardiac patches. The resulting robust, aligned ECM scaffold enhances cardiomyocyte maturation, showing promise for cardiac tissue engineering.
Area of Science:
- Biomaterials Science
- Stem Cell Biology
- Cardiovascular Research
Background:
- Extracellular matrix (ECM) from human induced pluripotent stem cells (hiPSCs)-derived cardiac fibroblasts (hiPSC-CFs) offers a biological scaffold for cardiac patches.
- hiPSC-CF-derived ECM (hiPSC-CF-ECM) can promote maturation of cardiomyocytes by providing cardiac-specific cues.
- Challenges exist in achieving sufficient robustness and thickness of hiPSC-CF-ECM.
Purpose of the Study:
- To optimize the culture period for hiPSC-CFs on micro-grated substrates to achieve appropriate ECM deposition, scaffold thickness, and mechanical strength.
- To create an aligned, robust, and cardiac-specific ECM scaffold for engineered cardiac patches.
- To evaluate the potential of the developed ECM scaffold in enhancing cardiomyocyte maturation and organization.
Main Methods:
- Cultured hiPSC-CFs on micro-grated substrates for 2 to 10 weeks to optimize ECM deposition and alignment.
- Fabricated an anisotropic hiPSC-CF-ECM scaffold, followed by decellularization.
- Analyzed ECM composition using liquid chromatography-mass spectrometry (LC-MS).
- Assessed scaffold mechanical properties using uniaxial tensile stretching.
- Evaluated hiPSC-derived cardiomyocyte (hiPSC-CM) alignment and maturation on the ECM scaffold.
Main Results:
- Optimized culture period of 6 weeks yielded an anisotropic nanofibrous hiPSC-CF-ECM scaffold with a thickness of 20.0 ± 2.1 µm.
- ECM composition analysis revealed cardiac-specific fibrillar and non-fibrillar collagens, and matricellular proteins.
- The scaffold demonstrated robust tensile resilience.
- hiPSC-CMs cultured on the scaffold showed alignment with ECM nanofibers and mature structural protein organization.
Conclusions:
- Successfully refined the culture duration for anisotropic hiPSC-CF-ECM to create a robust scaffold resembling the cardiac microenvironment.
- This completely biological, anisotropic, and cardiac-specific ECM scaffold holds significant potential for cardiac patch engineering.
- The optimized ECM scaffold promotes cardiomyocyte alignment and maturation, advancing cardiac tissue regeneration strategies.
