A Precision Medicine Approach For Non-invasive, Longitudinal, And Quantitative Monitoring Of Cardiac Tissue-engineered Scaffolds

3D bioprinting has revolutionized personalized and precision medicine by enabling the manufacturing of tissue constructs that precisely recapitulate the cellular and functional features of native tissues. In cardiac regenerative medicine, printed scaffolds have shown tremendous potential in repairing damaged heart, however, their clinical applications have been limited by the lack of precise noninvasive tools to monitor the patch function following implantation. By integrating state-of-the-art 3D bioprinting and photon-counting computed tomography (PCCT), this study introduces a new approach for bioengineering defect-specific scaffolds and monitoring their function. We prepared distinct CT-visible bioinks containing a variety of molecular or nanoparticle (NP) contrast agents, including iodine and gadolinium molecules, Au NPs, Gd 2 O 3 NPs, and iodine-loaded liposomes ( Fig 1A-B ). In vitro release experiments showed relatively rapid diffusion-controlled depletion of molecular contrast agents from scaffolds. In contrast, NP agents showed more stable encapsulation and only a partial, degradation-mediated release for up to 3 weeks of incubation ( Fig 1C-D ). Next, PCCT imaging was performed on various scaffold geometries printed using bioinks laden with Gd 2 O 3 or Au NPs. Results demonstrated CT visibility with differential contrast between different patch regions that corresponded to the designed geometries ( Fig 1E ). Finally, we evaluated the in vivo CT imaging of bioprinted patches after their subcutaneous implantation in a mouse model. CT images demonstrated adequate signal from implanted grafts ( Fig 1F ). Together, these results establish a novel precision medicine platform for non-invasive monitoring of medical devices which can open new prospects for a broad range of tissue engineering applications. Figure 1. 3D Bioprinting of CT-visible cardiac patches. A-B: Design of bioinks functionalized with molecular (left) and nanoparticle (right) CT contrast agents ( A ) and their bioprinting ( B ). C-D: In vitro release of contrast agents from printed patches. E: CAD design (left), CT image (middle), and PCCT material decomposition (right) for multi-contrast bioprinted scaffolds. F: In vivo CT imaging of printed patch, laden with Au NPs, implanted subcutaneously into a mouse torso.