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Bioprinting in cardiovascular tissue engineering: a review

ing heart and has the largest potential in regenerative 2. Conventional Engineering of Cardiac Tissues
[7]
medicine .
A potential medical solution is through injecting 2.1 Design Considerations
cells at infarct site or via intracoronary route [8–11] . There are several factors to consider when designing
Clinical trials have been performed to show safety and and engineering cardiac tissue. Firstly, the engineered
feasibility of using cells as therapy. Cardiosphere-der- cardiac tissue physiological properties should be sim-
ived cells (CDC), cardiac stem cells and bone marrow ilar or close to human myocardium [21–22] . Specifically,
cells have been injected to repair and regenerate the their modulus should be between 0.2 to 0.5 MPa at
myocardium since stem/progenitor cells are capable of end diastole with tensile strength of 3–15 kPa, con-
2
regeneration and differentiation [8–10] . For instance, car- tractile pressure of 2–4 mN/mm and electrical propa-
diac stem cell can differentiate into myocyte, smooth gation velocity of 25 cm/s.
muscle cell and endothelial cell lineages with potential Secondly, the engineered cardiac tissue should be
12
of dividing into 4.2×10 cells [12] . Increasing viable compatible with the native in the aspect of heteroge-
myocardium mass and promoting angiogenesis thro- neous cell population comprising of cardiomyocytes
ugh paracrine effects have been postulated as the suc- and non-cardiomyocytes [23] . Cardiomyocytes forms
cess factor in cell injection therapy [13,14] . However, the minority of cell population in heart yet give rise to
injecting cells directly has limitations such as low cell the bulk volume of the heart; while fibroblast domi-
survivability and low cell retention at injured site. nates the non-cardiomyocyte population and is in direct
Hence, fabricating a patch-like or scaffold as a vehicle contact with cardiomyocytes [23] . Other non-cardiomy-
for delivering cells is a potential solution to improve ocytes population includes endothelial cells, adipo-
cell retention and survivability at infarct site. cytes and neurons. The benefits of cardiomyocytes and
The concept of creating engineered tissue from cells, non-cardiomyocytes coupling include improvement in
biomaterials and biological molecules forms the fun- electrophysiology of engineered cardiac tissue and
damental of tissue engineering [15] . Tissue engineering production of survival and trophic signals to cardi-
[24,25]
is a field which applies the principles of engineering omyocytes .
and life sciences to develop biological substitutes that Thirdly, the architectural features of native heart are
can restore, maintain or improve tissue function [16] . different at various hierarchical levels. At the mil-
Specifically, cardiac tissue engineering aims to pro- li-scale level, aligned myofibers are induced by matrix
vide biological solutions to restore failing hearts and anisotropy while across the transmural direction, va-
[26]
has one of the largest potential in regenerative med- rying spatial arrangement of myofibers is present .
icine [17] . In the micro-scale, vascularization is needed as sup-
With advancement of three-dimensional (3D) prin- port system for nutrient/waste exchange in highly den-
[27]
ting, also known as additive manufacturing, various sed native myocardium . The design considerations
techniques have been applied in producing patient- are summarized in Figure 1.
specific biological substitutes, ranging from ortho- 2.2 Conventional Techniques in Cardiac Tissue
pedic implants [18–19] to scaffolds for tissue engineer- Engineering
ing [14,20] . Coupled with computer-aided technology, cus- In order to satisfy the above mentioned requirement,
tomized patch-like scaffold can be designed using ad- various techniques have been used to engineer
ditive manufacturing for cell delivery.
In this paper, design considerations for cardiac tis-
sue engineering will be highlighted. Conventional sca-
ffold fabrication method in cardiac tissue engineering
are discussed and evaluated. With the increase interest
in bioprinting for tissue engineering, the application of
bioprinting in cardiac tissue engineering is reviewed.
Lastly, different research areas that will bridge the gap
between engineered cardiac tissues with native cardiac

tissue are discussed. Figure 1. Design consideration in engineering cardiac tissue.
28 International Journal of Bioprinting (2016)–Volume 2, Issue 2