Advancing Cardiac Tissue Engineering: Microfluidic Systems and Heart ECM Integration

Recent advancements in the field of tissue engineering have yielded a novel culture system that significantly enhances the fabrication of human cardiac tissues. This system integrates a microfluidic platform with a heart extracellular matrix (HEM) hydrogel, designed to foster the maturation of tissues that more closely mimic the human cardiac microenvironment.

“The applications of cardiac tissues derived from human pluripotent stem cells are often limited due to their immaturity and lack of functionality. Therefore, in this study, we establish a perfusable culture system based on in vivo-like heart microenvironments to improve human cardiac tissue fabrication. The integrated culture platform of a microfluidic chip and a three-dimensional heart extracellular matrix enhances human cardiac tissue development and their structural and functional maturation.“, the authors explained.

The study details a culture system that supports the growth of cardiovascular lineage cells: cardiomyocytes (CMs), cardiac fibroblasts (CFs), and vascular endothelial cells (ECs), all derived from human induced pluripotent stem cells. The three-dimensional HEM hydrogel, developed from decellularized porcine heart tissue, maintains key extracellular matrix components that are crucial for cellular differentiation and tissue maturation.

 

The engineered cardiac tissues demonstrate substantial improvements in both structure and function. The integration of cell types in a dynamic flow system contributes to an environment that significantly advances the maturation of the cardiac tissues over traditional static culture methods. For instance, macroscale tissues (1-1.2 mm in thickness) maintained in the microfluidic device exhibit enhanced structural and functional properties due to improved nutrient and oxygen delivery facilitated by the dynamic flow.

The functionality of these tissues was validated through extensive testing, including:

Immunofluorescence Staining: Used to assess the presence and distribution of specific cellular proteins, confirming the cellular composition and maturation state of the tissues.

Proteomic Analysis: Provided insights into the protein expressions within the tissues, comparing them with native heart tissues to confirm the physiological relevance of the engineered tissues.

Gene Expression Profiling: Evaluated the expression levels of genes associated with cardiac maturation and functionality, further substantiating the enhanced maturity of the engineered tissues.

The HEM hydrogel demonstrated excellent biocompatibility, with endotoxin levels significantly below FDA thresholds (0.269 ± 0.003 EU/ml). These tests confirm the efficacy of the microfluidic chip and HEM hydrogel system in producing cardiac tissues that are not only structurally and functionally mature but also robust enough for practical applications in clinical research and therapy. The system’s utility spans several biomedical applications:

Drug Testing: The cardiac tissues are used to evaluate cardiotoxicity, showing differential responses to small molecules with varied levels of arrhythmia risk.

Disease Modeling: Conditions like Long QT Syndrome and cardiac fibrosis are effectively modeled, providing new insights into disease mechanisms and potential treatments.

Regenerative Therapy: The tissues show promising results in myocardial infarction treatment models, suggesting potential for regenerative medicine applications.

This study represents a significant step forward in the field of tissue engineering, providing a robust platform that not only enhances the maturation of human cardiac tissues but also offers a scalable solution for their application in drug testing, disease modeling, and regenerative therapies. The integration of a microfluidic chip and HEM hydrogel creates a more physiologically relevant model that could have substantial impacts on future research and therapeutic approaches.

“We anticipate that our versatile cardiac tissues will be established as practically available human in vitro cardiac models and provide therapeutic regimens for in vivo cardiac regeneration through further translational research“, the authors concluded.

Figures are reproduced from Min, S., Kim, S., Sim, WS. et al. Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications. Nat Commun 15, 2564 (2024). https://doi.org/10.1038/s41467-024-46928-y  under a CC BY 4.0 DEED Attribution 4.0 International license.

Read the original article: Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications

For more insights into the world of microfluidics and its burgeoning applications in biomedical research, stay tuned to our blog and explore the limitless possibilities that this technology unfolds. If you need high quality microfluidics chip for your experiments, do not hesitate to contact us.