Biomimetic design and fabrication of scaffolds integrating orientedmicro-pores with branched channel networks for myocardial tissueengineering

摘要

The ability to fabricate three-dimensional (3D)thick vascularized myocardial tissue could enablescientific and technological advances in tissue engineering and drug screening, and may accelerate itsapplication in myocardium repair. In this study, we developed a novel biomimetic scaffold integratingoriented micro-pores with branched channel networks to mimic the anisotropy and vasculature ofnative myocardium. The oriented micro-pores were fabricated using an ‘Oriented Thermally InducedPhase Separation (OTIPS)’ technique, and the channel network was produced by embedding andsubsequently dissolving a 3D-printed carbohydrate template after crosslinking. Micro-holes wereincorporated on the wall of channels, which greatly enhanced the permeability of channels. The effectof the sacrificial template on the formation of oriented micro- pores was assessed. The mechanicalproperties of the scaffold were tuned by varying the temperature gradient and chitosan/collagen ratioto match the specific stiffness of native heart tissue. The engineered cardiac tissue achievedsynchronized beating with electrical stimulation. Calcium transient results suggested the formation ofconnection between cardiomyocytes within scaffold. All the results demonstrated that the reportedscaffold has the potential to induce formation of a perfusable vascular network and to create thickvascularized cardiac tissue that may advance further clinical applications.