Biomimetic design and fabrication of scaffolds integrating oriented micro-pores with branched channel networks for myocardial tissue engineering

The ability to fabricate three-dimensional (3D) thick vascularized myocardial tissue could enable scientific and technological advances in tissue engineering and drug screening, and may accelerate its application in myocardium repair. In this study, we developed a novel biomimetic scaffold integrating oriented micro-pores with branched channel networks to mimic the anisotropy and vasculature of native myocardium. The oriented micro-pores were fabricated using an 'Oriented Thermally Induced Phase Separation (OTIPS)' technique, and the channel network was produced by embedding and subsequently dissolving a 3D-printed carbohydrate template after crosslinking. Micro-holes were incorporated on the wall of channels, which greatly enhanced the permeability of channels. The effect of the sacrificial template on the formation of oriented micro- pores was assessed. The mechanical properties of the scaffold were tuned by varying the temperature gradient and chitosan/collagen ratio to match the specific stiffness of native heart tissue. The engineered cardiac tissue achieved synchronized beating with electrical stimulation. Calcium transient results suggested the formation of connection between cardiomyocytes within scaffold. All the results demonstrated that the reported scaffold has the potential to induce formation of a perfusable vascular network and to create thick vascularized cardiac tissue that may advance further clinical applications.