Bizonal cardiac engineered tissues with differential maturation features in a mid-throughput multimodal bioreactor

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Cardiovascular Research

Background:

• Functional three-dimensional (3D) engineered cardiac tissue (ECT) models are crucial for drug screening and biological studies.
• Physiological cues, like mechanical forces, enhance cardiac maturation and functionality in vitro.
• Existing bioreactors have limitations in applying multiple or varied physical forces.

Purpose of the Study:

• To develop a millimetric-scale, microscope-integrated bioreactor capable of delivering multiple biophysical stimuli to ECTs.
• To investigate the effects of single auxotonic loading on ECT maturation and functionality.
• To compare the outcomes of different passive mechanical stimulation levels on cardiac cell behavior.

Main Methods:

• Development of a novel microscope-integrated bioreactor for applying multiple biophysical stimuli.
• Application of single auxotonic loading to 3D engineered cardiac tissues.
• Analysis of cardiomyocyte morphology, organization, and contractility under varying mechanical loads.
• Comparison of rat- and human-origin cardiac cell responses.

Main Results:

• Single auxotonic loading resulted in a bizonal ECT with distinct maturation patterns.
• High passive loading and static culture led to rounded cardiomyocytes with poor contractility.
• Low passive mechanical stimulation promoted cardiac cell maturation and organization in ECTs.
• ECTs exposed to low passive stimulation exhibited enhanced functionality.

Conclusions:

• Tailored mechanical stimulation is critical for optimizing engineered cardiac tissue development.
• A novel bioreactor system enables precise control over biophysical stimuli for advanced tissue engineering.
• Low passive mechanical loading is a key factor in achieving mature and functional cardiac tissue in vitro.