Scalable Production of Human Cardiac Tissues through hiPSC Encapsulation in Gelatin Methacryloyl

摘要

Biomaterials are widely used in cardiac tissue engineering to provide the three-dimensional(3D)structure and physiological cues required to closely mimic the native tissue environment.Engineered cardiac tissues have the potential to revolutionize our ability to understand and treat heart disease.However,progress toward commercial production of engineered cardiac tissues has been limited by the prohibitively complex process of assembly,which typically involves the use of multiple pre-differentiated cell types and numerous cell handling steps.We have previously shown that using poly(ethylene glycol)-fibrinogen(PEG-Fb)and our one-step cell handling approach provides the necessary structural and biological cues to support human induced pluripotent stem cell(hiPSC)differentiation into maturing engineered cardiac tissues with aligned sarcomeres and evidence of T-tubule presence.Our transformational approach produces cardiac tissue directly from hydrogel encapsulated human induced pluripotent stem cells,eliminating the need to pre-differentiate,dissociate and then re-assemble cardiac cells.Here we sought to determine if this one cell handling step approach for direct 3D cardiac tissue production could be translated for use with the printable material gelatin methacryloyl(GelMa)to directly produce 3D GelMa human engineered cardiac tissues(GEhECTs).