Establishing a 3D bioprinter in a biomedical research laboratory for the high resolution rapid prototyping of an auxetic cardiac patch

A recent development in biomedical research might hold the key to a successful revival of damaged cardiac tissue after Myocardial Infarction (MI): Cardiac patches are functioningcardiac tissue constructs, grown in-vitro, to replace and support the patient’s diseased tissue.The aim is to bridge mechanical and electrical stimulations and provide a stable substrate forcell-attachment and cell-growth. Scaffolds from biocompatible and biodegradable polymerslike polycaprolactone (PCL) provide good mechanical stability, but rarely provide the desired bioactive properties for tissue engineering. The solution for a successful patch might be the combination of hydrogel encapsulated cells with a stable polymer scaffold, to obtain a composite biomaterial.Certain microstructures can add favorable mechanical properties to a biomaterial for ademanding implantation site like the myocardium. This manuscript focuses on the development of a micropatterned PCL scaffold for an auxetic (when stretched, it becomes thicker perpendicular to the applied force) cardiac patch with a 3D printing approach.The installation- and training- phase on the 3D Bioprinter prior to the scaffold fabricatio nwas an important part of this project and was carefully documented. It gave insights into the capabilities and limits of the bioprinting system and fueled ideas for the future creation of amore advanced cardiac patch (e.g., scaffold material modifications, bioink surface-coating,ECM surface coating). High resolution printing over large areas with good structural integrity and high reproducibility was achieved and verified by the characterization of the 3D printed constructs.Tensile tests were conducted on the scaffolds. The test results proved that certain desired mechanical properties for cardiac tissue engineering, like an isotropic stiffness (Ex/Ey = 2.48) and ultimate strains close to the physiological range (7-20%) were successfully implemented into the PCL scaffold by incorporating the auxetic microstructure. Furthermore, a clearly negative Poisson’s ratio below -0.3, characteristic for auxetics, was shown for the constructs.Good biocompatibility (viability ~90%) and moderate cell-attachment to the scaffold was shown with a proliferation assay and via scanning electron microscopy. The cells were Human Umbilical Vein Endothelial Cells (HUVECs); seeded on the scaffold and observed over a period of 72h.The development of this Cardiac Patch scaffold prototype was a promising start for anongoing research project to find an efficient manufacturing method for a high-performance biomaterial for the treatment of MI.