Mechanical Characterization of hiPSC‐Derived Cardiac Tissues for Quality Control

Abstract

Heart disease is one of the leading death causes in developed countries. To facilitate heart rehabilitation, engineered cardiac implantation has emerged as a promising alternative to organ transplantation. Currently there is no quantitative standard to ensure the safety and functionality of the engineered cardiac tissues intended for clinical uses. In anticipation of the clinical application of the engineered cardiac tissues to heart disease patients, a suite of methods is assembled to evaluate the mechanical characteristics critical to cardiac functions, including contractility, viscoelasticity, and dynamic stress distribution. As a proof of concept, 3D bioprinted cardiac tissues derived from human induced pluripotent stem cells are tested. First, the engineered cardiac tissues labeled with particles are recorded and tracked to determine spatially and temporally variable contraction forces. Viscoelastic properties are measured using magnetic tweezers. The results are used to compute 3D force and stress distribution over the engineered tissue by finite element method. In summary, a framework is developed to assess clinical‐grade engineered cardiac tissues and determine the appropriate value ranges suitable for implantation. The results relating contractility, intrinsic mechanical properties, and stress distribution in the engineered tissue, can also inform better design for future fabrication of engineered tissues.

Versatile and High-throughput Force Measurement Platform for Dorsal Cell Mechanics

“…To compare our method to other force measurement methods, we also performed magnetic tweezers measurement to evaluate the dorsal traction forces transmitted via CTLA4-CD80 bonds, following the previously established protocol 48–50 . The results obtained from the magnetic tweezers showed traction force values exerted through CTLA4-CD80 were of the same order of magnitudes with the results using our microfluidics-based method with no significant difference between the two measurement methods (Supplementary Fig.…”

Mechanical stimulation enhances development of scaffold‐free, 3D‐printed, engineered heart tissue grafts

“…where a is the particle radius, E 0 and E 1 are the effective elastic moduli, μ 0 and μ 1 are the effective viscous frictions, and τ is the relaxation time. Additional details are found in (Park et al, 2018).…”

Development and Application of 3D Bioprinted Scaffolds Supporting Induced Pluripotent Stem Cells

“…Importantly, they built a computational model to visualize the 3D stress distribution to investigate the mechanical reliability of implantable tissues. Their method could serve as a nondisruptive framework that measures the contractility, beating patterns, and viscoelasticity of implantable cardiac tissues to be used in heart tissue regeneration [ 1 ].…”

“…The lack of tools for assessing promising drug targets impedes the development of treatments for various conditions, such as spinal cord injury and cardiovascular diseases. In addition, in some critical circumstances, such as organ transplantation, it is difficult to overcome the limited supply of suitable organ donors and a possible immune response to the organ transplant [ 1 ]. Therefore, approaches that enable tissue engineering for the development of innovative and effective treatments have been receiving increasing attention.…”