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Akter, et al.
ACE2/angiotensin-(1-7) and upregulated ACE/ for cell damage and is one of the major disadvantages of
angiotensin II have a greater impact on increasing the risk this technology .
[94]
of severity of COVID-19 patients with comorbidities .
[86]
Laboratory findings may help illustrate the 4.1.3. Acoustic droplet ejection bioprinting
risk factors of extreme disease outcomes. Decreased In acoustic droplet ejection bioprinters, heat, pressure,
lymphocyte and eosinophil counts, C-reactive protein, voltage, or shear stress are not applied. Rather, the bioinks
procalcitonin, and D-dimer concentrations are more are influenced to produce droplets through acoustic
noticeable in severe COVID-19 patients than in non- waves. However, slight disturbance while printing can
severe patients. These are some of the potential risk cause uncontrolled droplet ejection .
[95]
factors used to indicate disease progression [9,55,71,72,77] .
Moreover, estimating serious outcomes in 4.1.4. Microvalve bioprinting
COVID-19 patients are possible through the neutrophil- Pneumatic pressure is given to operate the microvalve
to-lymphocyte ratio, neutrophil-to-CD8 T cell ratio, for droplet generation. After applying the voltage pulse, a
+
platelet-to-lymphocyte ratio, and N terminal pro B type magnetic field is generated that pulls the plunger upwards,
natriuretic peptide [61,87-90] . Additionally, a biopsy study and the back pressure causes bioink ejection. Depending
observed less amount of peripheral CD4 and CD8 T on the pressure, this technique can be either continuous
cells cause lymphopenia in COVID-19. [91] . Changes in or not. Compared to other bioprinting techniques, the
serum D-dimer levels indicate the crosslink between microvalve bioprinting technique generates identical
the elevated D-dimer concentration and the dramatic droplets. In addition, cells printed through this technique
risk of thromboembolism, long-term complications, and retain their functionality and proliferation capability,
COVID-19-mediated mortality [5,87,92] . and their genotype and phenotype are preserved, making
this technique favorable for printing numerous types of
4. Different 3D bioprinting techniques cells .
[95]
3D bioprinting is an alternative to conventional
prototyping methods that utilize computer-aided designs 4.2. Material extrusion-based bioprinting
to develop new products, including cells, biomaterials, or Mechanical or pneumatic system is being utilized in
even living tissue. Bioprinting technology can be divided this technique to disperse bioink through a micro-nozzle
into three distinct categories, such as material jetting, for creating two-dimensional or 3D structures. This
material extrusion, and vat polymerization (Figure 1) . technology has multiple advantages, including the ability
[93]
to deliver different types of cells and materials and to
4.1. Material jetting disperse highly viscous bioinks containing a high number
Material jetting can be used to build different materials on of cells, pellets, and tissue spheroids. Compared to other
a pre-defined platform by jetting droplets. Different types techniques, the cell viability in this technique is above
of material jetting are available now. 90%, and the fabrication time is short. That is why, the
technique is advantageous to all .
[95]
4.1.1. Inkjet-based bioprinting
Different cells or biomaterials can be deposited as droplets 4.3. Vat polymerization-based bioprinting
through various dispensing forces. The heating reservoirs Vat polymerization-based bioprinting has better resolution
or piezoelectric actuators apply heat to create gasification and accuracy than other bioprinting technologies,
while generating and printing bubbles. On the other hand, making this technology attractive for fabricating
[93]
piezoelectric actuators give rise to pressure pulses to print complex extracellular matrices . Different types of vat
cells in a pre-determined place. Although inkjet-based polymerization-based bioprinting are described in the
bioprinting is faster, there is a high chance of cell damage following:
and lysis during the printing because of high temperature
and pressure. In addition, the droplets are not uniform in 4.3.1. Stereolithography
all the places . Stereolithography utilizes a laser or digital light projector
[94]
to crosslink the bioinks photolytically in a single printing
4.1.2. Laser-assisted bioprinting plane. The advantages of this technique include high
[95]
During laser-assisted bioprinting, a laser gets illuminated resolution, short printing time, and high cell viability .
on the donor ribbon layer so that the energy gets absorbed
and a high-pressure bubble gets created. The bubble 4.3.2. Digital light processing
influences the bioink to be deposited in the pre-determined Digital micromirror device is utilized in digital light
place as a droplet. This high laser energy is responsible processing to crosslink photocurable bioinks for
International Journal of Bioprinting (2022)–Volume 8, Issue 4 245

