Three-dimensional (3D) bioprinting fabricates 3D functional tissues/organs by accurately depositing the bioink composed of the biological materials and living cells. Even though 3D bioprinting techniques have experienced significant advancement over the past decades, it remains challenging for 3D bioprinting to artificially fabricate functional tissues/organs with high post-printing cell viability and functionality since cells endure various types of stress during the bioprinting process. Generally, cell viability which is affected by several factors including the stress and the environmental factors, such as pH and temperature, is mainly determined by the magnitude and duration of the stress imposed on the cells with poorer cell viability under a higher stress and a longer duration condition. The maintenance of high cell viability especially for those vulnerable cells, such as stem cells which are more sensitive to multiple stresses, is a key initial step to ensure the functionality of the artificial tissues/organs. In addition, maintaining the pluripotency of the cells such as proliferation and differentiation abilities is also essential for the 3D-bioprinted tissues/organs to be similar to native tissues/organs. This review discusses various pathways triggering cell damage and the major factors affecting cell viability during different bioprinting processes, summarizes the studies on cell viabilities and functionalities in different bioprinting processes, and presents several potential approaches to protect cells from injuries to ensure high cell viability and functionality.

Photocrosslinkable polymers such as gelatin methacrylate (GelMA) have various 3D bioprinting applications. These polymers crosslink upon exposure to UV irradiation with the existence of an appropriate photoinitiator. Two photoinitiators, Irgacure 2959 and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) are commonly used. This study systematically investigates the effects of photoinitiator types on the cell viability, physical properties, and microstructure in 3D bioprinting of GelMA-based cellular constructs. The main conclusions are: (1) during the 3D bioprinting, the cell viability generally decreases as the photoinitiator concentration and printing time increase using both Irgacure 2959 and LAP. At the low photoinitiator concentrations (such as 0.3% and 0.5% (w/v)), the overall cell viability is good within the printing time of 60 min using both Irgacure 2959 and LAP. However, at the high photoinitiator concentrations (such as 0.7% and 0.9% (w/v)), the overall cell viability using LAP is much higher than that using Irgacure 2959 within the printing time of 60 min; (2) after the 3D bioprinting, the photoinitiator types, either Irgacure 2959 or LAP, have negligible effects on the post-printing cell viability after crosslinking; (3) after the 3D bioprinting, GelMA samples cured with Irgacure 2959 have slightly larger pore size, faster degradation rate, and greater swelling ratio compared to those cured with LAP; (4) 3D GelMA-based vascular-like constructs have been fabricated using dynamic optical projection stereolithography, and the measured dimensions have been compared with the designed dimensions showing good shape fidelity.

Inkjet-based bioprinting have been widely employed in a variety of applications in tissue engineering and drug screening and delivery. The typical bioink used in inkjet bioprinting consists of biological materials and living cells. During inkjet bioprinting, the cell-laden bioink is ejected out from the inkjet dispenser to form microspheres with cells encapsulated. The cell distribution within microspheres is defined as the distribution of cell number within the microspheres. The paper focuses on the effects of polymer concentration, excitation voltage, and cell concentration on the cell distribution within microspheres during inkjet printing of cell-laden bioink. The normal distribution has been utilized to fit the experimental results to obtain the mean and standard deviation of the distribution. It is found that the cell distribution within the microspheres increases with the increase of the cell concentration, sodium alginate concentration, and the excitation voltage.