3D bioprinted functional and contractile cardiac tissue constructs

Abstract

Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However, its applications remain limited because the cardiac tissue is a highly organized structure with unique physiologic, biomechanical, and electrical properties. In this study, we undertook a proof-of-concept study to develop a contractile cardiac tissue with cellular organization, uniformity, and scalability by using three-dimensional (3D) bioprinting strategy. Primary cardiomyocytes were isolated from infant rat hearts and suspended in a fibrin-based bioink to determine the priting capability for cardiac tissue engineering. This cell-laden hydrogel was sequentially printed with a sacrificial hydrogel and a supporting polymeric frame through a 300-μm nozzle by pressured air. Bioprinted cardiac tissue constructs had a spontaneous synchronous contraction in culture, implying in vitro cardiac tissue development and maturation. Progressive cardiac tissue development was confirmed by immunostaining for α-actinin and connexin 43, indicating that cardiac tissues were formed with uniformly aligned, dense, and electromechanically coupled cardiac cells. These constructs exhibited physiologic responses to known cardiac drugs regarding beating frequency and contraction forces. In addition, Notch signaling blockade significantly accelerated development and maturation of bioprinted cardiac tissues. Our results demonstrated the feasibility of bioprinting functional cardiac tissues that could be used for tissue engineering applications and pharmaceutical purposes.

ECM concentration and cell‐mediated traction forces play a role in vascular network assembly in 3D bioprinted tissue

“…Recent work from our group has shown that anchoring of cellular constructs is critical for the development of organized tissue structures in 3D bioprinted tissue (Wang, Lee, Cheng, Yoo, & Atala, 2018). Such anchor points are understood to enable the intrinsic force in the system to induce compaction phenomenon within the tissue construct (H. W. Kang et al, 2016;Smith, Passey, Greensmith, Mudera, & Lewis, 2012).…”

3D bioprinting for cardiovascular regeneration and pharmacology

“…Thus, this construct effectively demonstrates the unique capability of bioprinting to print the complex trabecular structures of a whole heart through CAD modeling while using remarkably low-viscosity bioinks that would otherwise not be printable [195]. Atala et al also developed a contractile cardiac tissue construct with cellular organization, uniformity, and scalability through a 3D bioprinting approach [196]. The bioprinted cardiac tissue constructs were fabricated by processing three key components: a primary cardiomyocyte laden fibrin-based hydrogel, a sacrificial hydrogel, and a supporting polycaprolactone (PCL) polymeric frame.…”

“…The bioprinted cardiac tissue constructs were fabricated by processing three key components: a primary cardiomyocyte laden fibrin-based hydrogel, a sacrificial hydrogel, and a supporting polycaprolactone (PCL) polymeric frame. The cardiac constructs exhibited a spontaneous synchronous contraction in culture, and also displayed physiological responses to known cardiac drugs in terms of beating frequency and contraction forces [196]. A nano-reinforced hybrid cardiac patch laden with human coronary artery endothelial cells (HCAECs) was fabricated by UV-assisted 3D bioprinting to improved electrical, mechanical, and biological behaviors [197].…”

Nano‐ and Microfabrication for Engineering Native‐Like Muscle Tissues

“…It is achieved by the formation of gap junctions in cardiac muscles and smooth muscles, but not in skeletal muscles. Many researchers have successfully engineered hydrogel‐based cardiac muscle tissues using microfabrication technologies such as 3D bioprinting . And electromechanical coupling between CMs were observed.…”

“…Electronic readouts were obtained to reflect the contractile stresses. In another study, a 3D printed microspring device was used for the force measurement of cell‐laden cardiac patches . With the consistent stiffness in a wide range, the device could conveniently convert contracting motion to force.…”