3D BIOPRINTING TECHNIQUES - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 57

tissue spheroids and casting-based biocompatible processes to help achieve complex micro- and mac-
roarchitecture ( Valerie Liu Tsang, 2004; Derby, 2012 ). Perhaps one of the more exciting approaches is
“3D bioprinting”-based methods due to the advantages they offer over competing methods to fabricate
tissue and organ constructs. Among the advantages of this approach are
(1) Capability to build both 2D and 3D structures
(2) Ability to directly incorporate two or more different cell types in a defined spatial architecture in
multi-scale patterns
(3) Flexibility to achieve hybrid processes simply by switching out “tool” options as seen in
conventional manufacturing machines, such as CNC-based systems. This suggests that multiple
nozzle types or print heads can be incorporated to achieve heterogeneous structures.
(4) Digitally enabled processes allow faster clinical translation and eventual approval by regulatory
agencies. The control systems accompanying these processes offer the ability to control process
parameters to help achieve desired cellular construct characteristics.
3.2 DEFINITION AND PRINCIPLES OF 3D BIOPRINTING
3D bioprinting is the process of automated deposition of biological molecules on a substrate to
form a 3D heterogeneous functional structure with data derived from a digital model. The “print”
material used in bioprinting techniques, also known as bioinks, often include a judicious combina-
tion of living biological cells, polymers, chemical factors, and biomolecules to form a physical and
functional 3D living structure. The substrate is typically planar solid surfaces such as those of Petri
dishes, glass slides, or wells of culture plates, although the concept can be extended to nonplanar,
nonsolid, and flexible substrates. Living biological cells can be mammalian, insect, and plant-based
as well as viruses and bacteria. 3D bioprinting has its roots in the conventional “ink-jet” process
developed in the early 1950s that reproduces text and images from a computer file through droplets
of ink deposited on a substrate such as paper. Much of the 3D bioprinting techniques have also
grown from conventional additive manufacturing (AM) or layered manufacturing (LM) approaches.
The complexity of the 3D bioprinting techniques, when compared to AM-based methods of scaffold
fabrication, is attributed to the direct involvement of biological living materials during the fabrica-
tion process.
Hod Lipson in his topic “Fabricated: The New World of 3D Printing” highlights 10 principles of
3D printing as guiding beacons to disrupt the current notion of manufacturing by reducing key barriers
of time, cost, and skill level ( Lipson, 2013 ). We have highlighted 10 principles of 3D bioprinting that
will help shape the future of printing living tissue and organs for applications in regenerative medicine
and tissue engineering.
Principle 1: Physical replication of the living construct from a digital blueprint file.
Bioprinting machines receive initial manufacturing process data input from a digital model of the
construct. This digital model must serve as a repository of information that informs upstream and drives
downstream manufacturing process activities.
Principle 2: Product customization with high degree of feature variety
Decision-makers and end-users of the printed construct must have the freedom to specify feature
sets and functionalities of the construct with minimal complexity in manufacturing process activities.
Principle 3: Structurally heterogeneous product spanning more than two dimensional scales