A dual 3D bioprinting platform for engineering a thick anisotropic myocardial tissue with geometric vasculature - A dual 3D bioprinting platform for engineering a thick anisotropic myocardial tissue with geometric vasculature Project summary Cardiovascular disease associated with myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Adult cardiac muscle is thought to lack the ability to repair and regenerate after MI. Additionally, the death of cardiomyocytes stemming from MI activates an irreversible cascade of events leading to heart failure. Stem cell technologies, biomaterials, and various bioengineering approaches have been used to develop functional human-engineered tissue, which ultimately can serve to revolutionize the treatment of the damaged heart. The heart is a complicated, multicellular tissue with hierarchical, structural, and multifunctional characteristics. As such, this tissue presents a huge challenge to replicate through traditional tissue engineering approaches. Based on an anatomical and physiological understanding of cardiac tissue, one crucial challenge in cardiac tissue engineering is replicating the complex architecture (anisotropic myocardial fibers and geometric vasculature) within a cardiac tissue construct and improving its functional maturation. Thus, the objective of this project is to develop a novel advanced dual 3D bioprinting platform and multiple biomechanical stimulation strategies for engineering a novel thick, functional myocardial tissue with anisotropic myocardial fibers and geometric vasculature. Three specific aims of this project are: (1) to fabricate anisotropic myocardial constructs with geometric vasculature via dual 3D bioprinting, (2) to conduct a systemic investigation of hemodynamic behaviors and cell responses for the vascularized myocardial construct under rhythmic mechanical stimulation, and (3) to perform a functional evaluation with an in vivo pig MI model. We expect that innovatively integrating a dual 3D bioprinting platform with biomechanical stimulation will create a functional cardiac tissue with myocardial beating and mature microcirculation for MI treatment. If successful, it will contribute to the prevention of post-infarction ventricular remodeling and the restoration of normal cardiac function. Furthermore, it will not only help patients who are suffering from extensive physical and emotional pain to fight and win the battle against heart failure, but will revolutionize current bioengineering research, leading to a long-term solution for advanced clinical therapeutics.
