Figure 2. Bioengineered approaches to myocardial regeneration.

(A) Biophysical stimuli driving cardiomyocyte maturation: In a complex environment, a cardiomyocyte is exposed to electrical, mechanical, and biochemical stimuli, and to cell-cell and cell-matrix interactions. (B) Cardiac tissue engineering: Cardiac tissues formed between two pillars (left) or around a suture (right) in bioreactors imposing either mechanical forces (auxotonic loading at the left) or electrical stimulation (at the right). (C) Hierarchical architecture of cardiac tissues: The assembly of ventricular heart muscle represents a hierarchical arrangement that spans over several orders of spatial magnitude: from the alignment of actin-myosin complex within a sarcomere, to the alignment within myofibrils, the organization of myofibrils in a myocyte, and the coupling between myocytes to form anisotropic, laminar cardiac tissue. (D) Geometric control of cell alignment: in vitro recapitulation of cell alignment at the micrometer scale. Panels B, left and right, are reproduced with permission from references [8] and [68]. Panel D is reproduced with permission from reference [69].