Three‐dimensional bioprinting human cardiac tissue chips of using a painting needle method

Abstract

Three‐dimensional (3D) printers are attracting attention as a method for arranging and building cells in three dimensions. Bioprinting technology has potential in tissue engineering for the fabrication of scaffolds, cells, and tissues. However, these various printing technologies have limitations with respect to print resolution and due to the characteristics of bioink such as viscosity. We report a method for constructing of 3D tissues with a “microscopic painting device using a painting needle method” that, when used with the layer‐by‐layer (LbL) cell coating technique, replaces conventional methods. This method is a technique of attaching the high viscosity bioink to the painting needle tip and arranging it on a substrate, and can construct 3D tissues without damage to cells. Cell viability is the same before and after painting. We used this biofabrication device to construct 3D cardiac tissue (LbL‐3D Heart) using human‐induced pluripotent stem cell–derived cardiomyocytes. The constructed LbL‐3D Heart chips had multiple layers with a thickness of 60 µm, a diameter of 1.1 mm, and showed synchronous beating (50–60 beats per min). The aforementioned device and method of 3D tissue construction can be applied to various kinds of tissue models and would be a useful tool for pharmaceutical applications.

Advances in 3D bioprinting technology for cardiac tissue engineering and regeneration

“… The engineered body showed excellent myocardial tissue-like functions. [ 148 ] Gelatin hiPS-CM & endothelial cell (EC) Decellularized porcine omentum A complete, thick vascularized cardiac patch and heart were printed of in one step, and were tested in vitro. The realistic heart-like active structure with vascularization presented human affinity and could potentially be suitable for future clinical use.…”

“…4 Full-fledged and high-resolution cardiac structures engineered by advanced 3D bioprinting. Through accurate printing and cross-linking of cell-loading cardiac bioink, the original structure of heart can be realistically reproduced in construction of: linear columnar ( A ) [ 85 ], grid-like pattern ( B ) [ 67 ], spherical cluster ( C ) [ 148 ], rectangular parallelepiped ( D ) [ 86 ], valentine heart-shaped material ( E ) [ 72 ], cube-shaped block ( F ) [ 71 ], perforated column ( G ) [ 84 ], conical container ( H ) [ 102 ], four-chamber sagittal plane ( I ) [ 102 ], heart valve-like structure ( J & K ) [ 68 , 102 ], left heart with large vessel-like construction ( L ) [ 68 ], right ventricle-like construction ( M & N ) [ 90 ], and micro vascularized HEHT ( O ) [ 117 ]. …”

“…B. Spontaneous muscle-like contraction after stabilization can be documented by video (b1 and b2) [ 72 , 90 ] and quantification (b3) [ 86 ]. C. The micro-engineered cardiac tissues can also excite stable cardiomyocyte-like depolarization-repolarization action potentials (c1 and c2) [ 102 , 148 ]. D. Dynamic calcium transient processes of the advanced 3D bioprinted functional cardiomyocytes may be real-time detected (d1 and d2) [ 72 , 90 ].…”

“…Another important characteristic that is closely related to the estimation of the contractile functioning of a heart (especially the left and right ventricles) is the electrophysiology mediated by the Na + -K + exchange pump, namely, the active SAP of 3D-CTE [ 147 ]. On the one hand, when pacemaker CMs (or the encapsulated stem cells destined to form pacemaker CMs) were employed in the printing system, even the use of a fine-needle pendant drop printing could excite a typical QRS/T waveform [ 148 ]. On the other hand, for the 3D-CTE without typical pacemaker CMs, the regular ventricular-like SAP waveform could also be well triggered or respond to the stimulation of additional electrical signals [ 102 ].…”

Biomimetic microsystems for cardiovascular studies

“…These cellularized microfluidic-based platforms replicate key microenvironmental features that enable the spatial and temporal control of cell growth and biochemical cues. Primary cells such as mammalian (16), embryonic (17,18), and induced pluripotent stem cell (iPSC) derived cells (19)(20)(21)(22)(23)(24)(25)(26) are commonly used cell sources in cardiovascular chip models. In cardiac modeling, most biomimetic chip platforms focus on cardiomyocytes as they are considered the workhorses of the heart.…”