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International Journal of Bioprinting 3D printing of smart constructs for precise medicine

micro-electrodes and micro-actuators can be fabricated extrusion (e.g., nano carbon tubes/fibers, magnetic
through accurate jetting of conductive polymer-loaded particles, and conductive materials) to induce smart
inks; consequently, a glucose sensor can be successfully behaviors in the printed 3D constructs. Moreover, through
constructed on the glucose sensor can be successfully the direct writing feature of FMD, multiple materials can
constructed on a paper to produce an integrated wearable be collaboratively deposited using different printing heads
biomedical device . Moreover, by controlling the printing in a single process to produce a construct with complex
[39]
parameters, droplets with uniform dimensions, shapes, and architecture and heterogeneous compositions [42,44] . The
amount payloads can be produced, which are conducive coprinting manner can unify the mechanical property of
to engineering responsive drug carriers with controlled structural materials and the responsive capacity of smart
dosage formulation and release kinetics. In a representative inks. Thus, various smart devices, such as strain sensors,
study, thermoresponsive core-shell polymer microcapsules smart tires, and cable-driven soft fingers, can be produced.
for controlled drug release were fabricated through inkjet
printing . As the sensing temperature decreased to 2.3. 3D bioprinting techniques
[40]
around 37°C, the thermoresponsive capsule dynamically The fields of tissue engineering and regenerative medicine
changed from a swollen structure to a collapsed structure, aim to facilitate the repair and regrowth of damaged tissues
resulting in the appearance of nanopores, which served as and organs, which usually requires key participants, such
a retractable gate to control drug release and retention. as engineered cells and biomolecules, to improve the
interactions between the engineered constructs and
2.2.4. Fused deposition modeling
the body of the host. The aforementioned 3D printing
Fused deposition modeling (FDM) is a commonly used techniques can be used to build complex 3D constructs
material extrusion technology for rapid prototyping. using various biomaterials, including bioactive polymers,
The principle of the FDM process is shown in Figure 3D. metals, ceramics, and glass, which help in producing
A thermoplastic polymer (e.g., polycaprolactone [PCL], implants and surgical instruments for personalized
[41]
polylactic acid [PLA] , and polyurethane [PU]) is melted medicine. However, their hash printing environments
into a liquid state at a temperature higher than glass render them unsuitable for use with bioinks. For instance,
transition point and then extruded through a head nozzle to the application of UV irradiation in SLA can trigger cell
form a filament. These filaments can be directly deposited apoptosis due to DNA damage; the inkjet printing binders
following computer-generated design in a layer-by-layer are usually cytotoxic, and the high temperatures used in
manner to generate a 3D structure. The thickness of the FDM and SLS inevitably cause cell death and denaturation
layers, the diameter of nozzles, and printing speed (speed of of proteins. Although cells and biological factors can
nozzle movement) are important factors in modulating the be introduced in 3D-printed structures through post-
resolution of printing. Reducing the diameter or increasing processing methods, such as seeding, binding, and coating,
the moving velocity of nozzles produces thinner filaments, these approaches are limited because precision is needed
thereby improving the printing resolution. However, to produce biomimetic living constructs. To overcome
the determination of these parameters depends on the these challenges, the 3D bioprinting techniques were
properties of applied materials (e.g., glass transition point designed to directly use living cells, biomaterials, and
and viscosity of molten polymers). Taking acrylonitrile biomolecules as fundamental building blocks to fabricate
butadiene styrene (ABS) as an example, empirical studies 3D constructs . The prevalent 3D bioprinting techniques,
[45]
have explored optimal printing parameters, the layer height such as light-assisted, microextrusion-based, and inkjet-
is 0.1 – 0.3 mm, and the melting extrusion temperature is based approaches, are summarized in this section.
above 180 – 200°C .
[42]
2.3.1. Light-assisted 3D bioprinting
Unlike other 3D printing techniques, FDM is a relatively
simple fabrication process that does not require any solvent Despite the high resolution of laser-based 3D printing
or sophisticated laser system, but it needs polymeric fiber techniques, the detrimental effects of commonly used UV
coils that continuously supply materials and mechanical irradiation on cell viability and molecular stability limit
platforms to control motions . This convenient approach their application in engineering biological constructs
[43]
permits FDM to be a convenient 3D printing technique for (Figure 4A). UV light is electromagnetic radiation with
fabricating smart constructs, if environment-responsive wavelengths ranging from 10 to 400 nm, which can be
materials or shape-memory polymers technically possess further categorized into UVA (320 – 400 nm), UVB (275 –
thermoplastic characteristics. Conversely, if the primary 320 nm), and UVC (<275 nm). UVA is the least harmful to
input material does not possess any stimuli-responsive the human body compared to the other shorter wavelengths.
ability, other functional additives should be used before Treatments involving UVA irradiation for a short period

Volume 9 Issue 1 (2023) 235 https://doi.org/10.18063/ijb.v9i1.638