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A perspective on 4D bioprinting

Figure 1. Three approaches in 4D bioprinting.

self-assembly or self-organization. Micro-droplets of modating processes. The process design could be
cells are precisely deposited into a certain pattern, and stepwise, relating the type and degree of stimulation to
then the pattern changes over time due to cell commu- the type and degree of change. The process may or
[8]
nication and self-organization . In this approach, self- may not be reversible, but it is preferable to have the
assembly is stimulated to occur, but what could sti- process being reversible in the design.
mulate the pattern to change is not clear yet. It is dif- Thirdly, the programmable design must be printa-
ficult to compare these three approaches and conclude ble by existing bioprinting processes. It could be
what is better and what is not, since all are sup- printing in 2D and then folding into 3D or printing in
ported by limited study at the current stage. Nonetheless, 3D and then changing into another 3D configuration.
every approach is interesting and worth further explo- Lastly and most importantly, the self-assembly or
ration in future. self-organization must not occur naturally, but instead
Since current approaches are different from each it must be driven by cells or biomaterials and trig-
other and there is no consensus on the exact form of gered by external stimulation, otherwise it does not
4D bioprinting, we would like to propose the follow- suit our definition of 4D bioprinting. In 4D bioprinting,
ing definition for 4D bioprinting to accommodate all the post-printing path in the fourth dimension needs
current studies and perhaps future studies as well. to be manually manipulated. Therefore, fusion of 3D
4D bioprinting refers to groups of programmable printed tissue spheroids into certain shape is not con-
self-assembly, self-folding or self-accommodating tech- sidered as 4D bioprinting, because tissue fusion pro-
nologies which include three main defining or essen- cess is natural, unless the printed spheroids can hold
tial components: (i) man-made and not nature-made its as-printed state and start to fuse upon external sti-
[9]
programmable design, (ii) 2D or 3D bioprinting pro- mulation. Furthermore, in some reported cases , cell
cess, and (iii) post-printing programmable evolving contraction and cell migration for cell-driven self-
of bioprinted constructs which could be driven by cells folding and self-assembly is actually also a natu-
or biomaterials and triggered by external signals. ral biological process. The folding of the cell origami
This definition of 4D bioprinting has several fea- is not a programmed design, also because the se-
tures. Firstly, 4D bioprinting is not defined as a single quence of the folding planes is totally random, neither
technology. Similar to additive manufacturing, it is controlled nor repeatable.
defined as a family of technologies based on different 3. Conclusion
principles.
Secondly, there must be a man-made programmable In summary, there are clear differences between
design for self-assembly, self-folding and self-accom- 3D bioprinting and 4D bioprinting. The major diffe-

4 International Journal of Bioprinting (2016)–Volume 2, Issue 1