• A study of the effect of the 3D bioprinting, microfluidic in cardiac tissue engineering
  • Niloofar Torkzadeh,1,* Mozhgan Shirazi,2
    1. Department of Biochemistry, Islamic Azad University, Falavarjan, Iran
    2. Department of Biology, Science and Research branch, Islamic Azad University, Tehran, Iran


  • Introduction: Cardiovascular diseases (CVDs) have been recognized as a major concern for global health among non-communicable diseases, and despite half century of advance in cardiovascular science and preventive medicine CVDs continue to yield high mortality and morbidity rates worldwide. 2D cell culture models offer simpler more inexpensive and higher throughput platforms for discovery and screening. Microfluidic technology allows fabrication of systems populated by human cells that recapitulate some aspects of organ function and can be used to probe key molecular or cellular events in a physiologically relevant construct to explore the origins of acute or chronic disease.
  • Methods: 3DBP, which similar to traditional 3Dprinting, is also an additive manufacturing technique but the printed inks or resins are replaced with cells only the biomaterial and cells mixture. 3DBP spatially controls the deposition of bioink, allowing for the fabrication of functional living constructs with 3D customized architecture.
  • Results: The cardiovascular system is a closed pressurized system with utilizes cycle pimping to enable convective transport of oxygen and nutrients throughout the body. Tus the cells and extracellular matrix (ECM) that comprise cardiac and vascular tissue must withstand cyclic pressures and hemodynamic fluid stresses of magnitudes that vary with location within the circulatory system. As result the structure and composition of ECM within the cardiovascular system is highly complex and tissue specific. For example while vessel ECM is generally composed of fibrillar collagen, elastic fibers, fibronectin, fibrillin and proteoglycans the ratio of collagens and elastic fibers very across vessels. Collagens function to provide tensile strength and together with elastic fibers ensure vessels elasticity and thus proximal arteries that experience higher well tension have a higher number of collagens and elastin than distal arteries and veins. Due to their high self-renewal capacity and ability to generate any cell type of the human body, pluripotent stem cells (PSCs) are becoming an attractive alternative for cardiac. These PSCs can either be derived from the inner cell mass of the blastocyst, named embryonic stem cell (ESCs) or forced expression of pluripotency genes through the delivery of the reprogramming factors OCT3/4, SOX2, Klf4, and cmyc to somatic cells termed induced PSCs (iPSCs). In particularly, human iPSC (hiPSC) derivatives better capture patient specific physiology besides surpassing the ethical concerns associated with human ESC (hESC). Acquired knowledge on stem cell biology together with the advances in psc technology has allowed the establishment of robot differentiation protocols capable of obtaining every subtype of CM (ventricular, atrial, and pacemaker) with a high degree of purity. Hydrogel matrix stems present a 3D environment similar to that of native tissues, and cells can be encapsulated within hydrogel matrices homogeneously. Moreover, external stimulation approaches such as mechanical stimulation or electrical stimulation have been applied control 3D cell alignment and elongation within hydrogel scaffold. However, the inconvenience of these external stimulation methods limits their application. Shin et al. presented an interesting method for engineering 3D multi layered constructs using layer by layer assembly of cells separated self-assembled grapheme oxide based thin films. This multi layered construct showed strong spontaneous beating and frequency dependent opening/ closing actuation under allow external electric field.
  • Conclusion: 3DBP is a promising technique for CTE owing to its ability to print heterogeneous structures and make full use of advanced achievements in cell and material engineering field. To date inducing maturation of hpsc_CMs is a challenge in the field limiting their use in clinical setting. Benchmarked on a chip engineered cardiac tissue, although promising still need show standardization and high throughput compatibility to contribute to more reliable results than commonly used platforms, as well as reduction of costs to expedite drug development.
  • Keywords: cardiovascular diseases (CVDs), tissue engineering, 3D bioprinting, microfluidic, organ as a chip,