Page 34 - IJB-2-2

Bioprinting in cardiovascular tissue engineering: a review

as structural support for cell depositions. For example, tage of LIFT over other orifice-based techniques, such
cell sheet technology is capable of fabricating cellular as inkjet and extrusion, is the ability to print materials
compound without using solid scaffolds for structural of wide viscosity range. Hence, high cell loading den-
8
support in the process. The process involves culturing sity (10 cells/mL) can be printed using LIFT.
cells on modified thermo-responsive polymer surface.
With temperature change, the tissue culture is dis- 3.2 Material Extrusion
lodged as an entire layer of cell with cell-cell junction This technique is a combination of an automated ro-
intact. Primary neonatal rat cardiomyocytes, induced botic system for extrusion and a dispensing system for
pluripotent stem cells, C2C12 mouse myoblasts have fluids [61] . The dispensing system can extrude hydrogel
been fabricated as cell sheets [53–56] . from the nozzles, producing defined structures. The
As cell sheets can be transplanted in layers, cells automated robotic system for extrusion printing is
retention at the infarcted sites is higher as compared to generally powered by either a pneumatic [62–70] or a
injecting cells. Furthermore, cell sheets provide mi- mechanical pump [71,72] . These pumps act by applying a
nimally invasive solution as they are transplanted into positive pressure on the hydrogel causing it to flow
the host tissue without sutures. Vascularization can be out of the nozzle. Additionally, valves can be placed at
facilitated with specifically designed bioreactor [57] . the nozzle to create droplets by regulating the flow of
However, delivering cell sheet for restoration of in- the hydrogel within the syringe [73] .
farcted heart remains inconclusive. For instance, the
number of cells in cell sheet is approximately 9.5 × 3.3 Future Prospect
10 4[55] while number of damaged cells during infarction
is approximated at 8 × 10 6[3] . The effectiveness of cell The current state-of-the-art involves several research
sheet in terms of replacing damaged cells requires fur- groups using bioprinting for construct containing pat-
ther research since the difference is several magnitude terned heterogeneous cells, structures with complex
lower. shape and microchannels for vascularization (Figure 2
and Table 2). However, the differences between bio-
3. Bioprinting: The New Paradigm in Engineer- printed cardiac tissue compared to native cardiac tis-
ing Cardiac Tissues sue still require further research, as shown in Figure 3.
(1) Cell Source for Bioprinting
Bioprinting, a variant of additive manufacturing or 3D The ideal cell type that can be used for engineering
printing, uses computer-aided processes to pattern and in vivo solutions for cardiovascular diseases has not
assemble living and non-living materials with a pre- been identified. Furthermore, the protocol for cell iso-
scribed two-dimensional (2D) or 3D organization [58] . lation from endocardium, epicardium and cardiac fi-
However, bioprinting shall not be used interchangea- broblast have not been developed while the relation-
bly with 3D printing of inert materials [59] . Most im- ship between cardiomyocytes and non-cardiomyocytes
portantly, bioprinting offers the advantage to control has not been established [80] . These are intrinsic bio-
shape and material in multi-material printing. This logical questions that remain to be answered in the
unique capability of multi-material printing enables field of cardiac tissue engineering. Due to the limita-
printing of anatomically relevant structures in fabri- tion in vascularization, fabrication of full thickness
cating cardiac tissues. Of the many bioprinting tech- cardiac tissue has not been achieved. A vascular net-
niques, material jetting and material extrusion systems work is needed to facilitate nutrient transportation in
have been used to produce engineered cardiovascular an engineered cardiac tissue due to high loss of car-
models (Figure 1). diomyocytes during infraction. However, conventional
methods in fabricating engineered heart tissue showed
3.1 Material Jetting
limited advancement in this prospect.
This involves droplet displacement of material. Met- (2) Micro / Nano Features
hods using this technique are piezoelectric/thermal ink- Conventional approaches have achieved cell align-
jetting, and laser induced forward transfer (LIFT) [60–61] . ment of myocytes at planar level through the under-
Density of cell printed can be controlled by overprint- standing of cell-material interactions. The cell align-
ing over a specific area. Moreover, different cell types ment can be conformed and guided using defined
can be printed within a construct. One distinct advan- spaces as shown by cell alignment along the spun fi-

30 International Journal of Bioprinting (2016)–Volume 2, Issue 2