Drug response analysis for scaffold-free cardiac constructs fabricated using bio-3D printer

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Cardiovascular Research

Background:

• Scaffold-free 3D cardiac constructs using human induced pluripotent stem cells-derived cardiomyocytes (iPSCs-CMs) are valuable for drug testing.
• Previous methods for evaluating cardiac construct function were limited.

Purpose of the Study:

• To develop and validate a novel method for measuring contractile force in 3D cardiac constructs.
• To assess the utility of this method for evaluating drug response and cardiotoxicity.

Main Methods:

• Fabricated scaffold-free 3D tubular cardiac constructs using a bio-3D printer and needle array.
• Measured needle tip displacement upon construct contraction to quantify contractile force and beating rate.
• Assessed drug effects using isoproterenol, propranolol, and blebbistatin.
• Evaluated cardiotoxicity with doxorubicin, measuring contraction and cell viability.

Main Results:

• The method successfully quantified contractile force and beating rate by analyzing needle tip movement.
• Drug responses were discernible: isoproterenol increased movement, while propranolol and blebbistatin decreased it.
• Doxorubicin treatment showed decreased cell viability correlated with reduced needle tip movement, indicating cardiotoxicity.

Conclusions:

• A novel, non-invasive method effectively measures contractile force in iPSCs-CMs cardiac constructs.
• This technique provides a reliable platform for evaluating drug efficacy, cardiotoxicity, and cardiac responses.
• The developed method supports advancements in preclinical drug screening and cardiovascular research.