3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts

Abstract

Generation of thick vascularized tissues that fully match the patient still remains an unmet challenge in cardiac tissue engineering. Here, a simple approach to 3D‐print thick, vascularized, and perfusable cardiac patches that completely match the immunological, cellular, biochemical, and anatomical properties of the patient is reported. To this end, a biopsy of an omental tissue is taken from patients. While the cells are reprogrammed to become pluripotent stem cells, and differentiated to cardiomyocytes and endothelial cells, the extracellular matrix is processed into a personalized hydrogel. Following, the two cell types are separately combined with hydrogels to form bioinks for the parenchymal cardiac tissue and blood vessels. The ability to print functional vascularized patches according to the patient's anatomy is demonstrated. Blood vessel architecture is further improved by mathematical modeling of oxygen transfer. The structure and function of the patches are studied in vitro, and cardiac cell morphology is assessed after transplantation, revealing elongated cardiomyocytes with massive actinin striation. Finally, as a proof of concept, cellularized human hearts with a natural architecture are printed. These results demonstrate the potential of the approach for engineering personalized tissues and organs, or for drug screening in an appropriate anatomical structure and patient‐specific biochemical microenvironment.

Biomaterials for Personalized Cell Therapy

“…Schematic models and fluorescent images of perfused vascular 3D‐printed tissues from: A) fully personalized cardiac patches fabricated from ECM‐derived hydrogels and CT images to match a patient's biology and anatomy. Adapted with permission . Copyright 2019, Wiley‐VCH.…”

“…The cardiomyocytes and endothelial cells are separately mixed with the personalized hydrogel to form bioinks for cardiac and vascular tissues, respectively. Finally, a personal cardiac patch is printed using a computer‐aided design of the patient's left ventricle based on anatomical data from computerized tomography (CT) images of the patient's heart and mathematical modeling of blood vessel architecture (Figure ) . Although advances in both imaging and 3D printing technology are needed to precisely recapitulate the complete vascular network with small diameter vessels, this report marks an important progression in the development of personalized tissue engineered therapies.…”

From Shape to Function: The Next Step in Bioprinting

“…The alginate‐based support bath was enzymatically degraded to gently harvest the fragile objects. Reproduced under the terms of the Creative Commons CC‐BY 4.0 License ( https://creativecommons.org/licenses/by/4.0/) . Copyright 2019, The Authors, Published by Wiley‐VCH.…”

“…Another option would be to address the problem from the support bath side. Recently another suitable system has been developed, consisting of alginate microparticles and xanthan gum, to support the print and curing of an omental ECM‐based bioink . This support setup tolerated a broader range of temperatures and can be enzymatically or chemically degraded to gently harvest the printed object.…”

“…Technologies like digital light processing bioprinting have potential to print directly intricated hollow structures and convoluted porosities, whereas printing in supporting baths has been used for extrusion‐based printing of free‐form vessel‐like structures. Patient‐specific, vascularized heart constructs have been obtained through printing within an alginate‐xanthan gum supporting bath, using an momentum‐derived dECM bioink, with a vascular network printed using a sacrificial gelatin ink . In a different study, spiraling, straight and stenotic vessel‐like channels have been printed using a fugitive ink, based on a shear‐thinning and reversible supramolecular hydrogel, formed by a blend of cyclodextrin‐ and adamantane‐modified HA.…”