Image-Guided Cardiac Regeneration via a 3D Bioprinted Vascular Patch with Built-in CT Visibility

Abstract

Cardiac patch-based regenerative therapies have shown great promise in the treatment of myocardial infarction (MI). The clinical applications of patch devices, however, face major limitations mainly due to the inadequate integration of typically nonvascular implanted grafts with the recipient heart muscle tissue, the lack of patient and damage specificity, and insufficient perfusion. Here we present a new generation of cardiac patch devices with customized geometry and vasculature to closely correspond to those of the recipient heart tissue, while providing in-situ imaging properties. Incorporation of multiple computed tomography (CT) contrast agents within hydrogel bioinks enabled longitudinal and quantitative tracking of patch scaffolds both in vitro, in static versus flow culture conditions, and ex vivo using photon-counting CT (PCCT). We also investigated the cardioprotective impact of the bioprinted vascular patch in a rat model of MI. PCCT distinguished the signal from multiple contrast agents to assess perfusion within the vascular patch in vitro, as well as the surgical location, integration and degradation of patch ex vivo. Results establish a novel approach for developing vascular cardiac patches with noninvasive imaging capabilities, addressing critical challenges in monitoring patch engraftment and function, as a powerful tool for advancing translational cardiac regenerative therapies and optimizing clinical outcomes.

Keywords: 3D bioprinting; PCCT; bioink; contrast agent; longitudinal quantitative imaging; nanoparticle; photon-counting computed tomography; tissue engineering scaffolds.