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

thermo-electric, dielectric, halochromic, and chromogenic female reproductive tract. A sperm can be unleashed to
materials, have been intensively explored for engineering deliver drugs to cancer cells by magnetically navigating
smart constructs [126] . Several categories of 3D printing and sperm-embedded microrobots fabricated using a TPP
bioprinting techniques are available for full exploitation of 3D printing technique toward a HeLa tumor spheroid.
their functions (section 2). Each of these methods shows Other studies have also innovatively investigated the
a unique ability to process different types and forms of shape-morphing of cell-laden 3D constructs bioprinted
biomaterials. For instance, photocurable polymers, shape- using stimuli-responsive bioinks [141] . For instance,
memory alloys, low viscosity liquids, and thermoplastic Luo et al. 3D bioprinted a bilayered scaffold with an
[13]
polymers are specifically adaptable to SLA, SLS, 3D inkjet, orthogonal structure using alginate/polydopamine and
and FDM techniques, respectively. Furthermore, commonly alginate/GelMA-containing human embryonic kidney
used 3D bioprinting techniques can embed living cells within cells (HEK 293T). On near-infrared irradiation-induced
the printed structures. Therefore, 3D printing and bioprinting dehydration, the biphasic scaffold can undergo tailored
technique cover a wide range of smart biomaterials. Liquid structural transformation within several minutes while
metals [127] , liquid crystal polymers [128] , hydrogels [129] , shape- retaining high cell viability after 14 days of culturing. With
memory polymers [130] , and smart composites [131] have the application of 3D bioprinting in engineering live smart
been used as printable materials in pioneering studies, constructs, 4D bioprinting and biofabrication of advanced
demonstrating the unparalleled material compatibility of 3D artificial tissues may be achieved.
printing and bioprinting techniques.
5.2. Considerations of 3D-printed smart constructs
Complex structural and compositional designs in precision medicine applications
can further enhance the intelligence of some stimuli-
responsive materials; consequently, advanced smart Despite the great potential for precision medicine
structures can be developed. For example, smart construct application, 3D-printed smart constructs should be
structures can be designed in bilayers or multiple layers, further developed and enhanced, awaiting future efforts
anisotropic alignments, and programmed patterns to for continuous innovations. Fundamental material
achieve the desired shape transformation responsive formulation and desired smart functions should be
morphing behaviors, such as rolling [132] , compression [133] , matched to develop advanced smart constructs for tissue
torsion [134] , stretching [135] , folding [136] , and complex actions regeneration, drug delivery, and health monitoring.
(e.g., swimming, walking, and crawling [137] ). In addition, In general, artificial tissue, drug carrier, and biosensors
the distribution or gradient of multiple components has are usually implanted into the patients’ body or placed
been applied to smart composites to establish stimuli- in close contact with human tissues. Therefore, biosafety
triggered transformation [138] , degradation [139] , and payload becomes the principal requirement for smart constructs.
release [140] . Despite these advanced functions, developing Regardless of smart properties, the applied biomaterials
sophisticated designs using other manufacturing must possess several critical performances, including
approaches are difficult. 3D printing and bioprinting have non-immunogenicity, non-toxicity, and biocompatibility.
become pivotal techniques for producing smart constructs Conversely, good printability is an indispensable
because they provide the flexibility to precisely position performance of smart biomaterials in 3D printing
multiple biomaterials and bioinks to construct a 3D techniques. In addition, strong magnetoelectric signal,
assembly with the desired structures and compositions. extreme pH, intense irradiation, and high ion concentration
[28]
Cell therapy, cell-based drug delivery system, and may trigger cell death and tissue damage . Considering
functional in vitro tissue models, organ-on-a-chip, and the patients’ health, the stimuli applied to activate smart
organoids have fully demonstrated that living systems are constructs must be mild.
desirable for biomedical and clinical applications because There are also additional specific requirements for
they can comply with physiological processes and respond the design of materials in each type of application. For
to natural signals from the human body (e.g., pH, ion, tissue repair and regeneration, biomaterials and bioinks
bioelectricity, body motion strain, and infectious signals). must be cell-friendly to promote cell activities and
Equipped with smart properties, these living constructs generate functional tissues. Accordingly, mechanical,
may achieve unique performances. 3D bioprinting compositional, and structural features of materials
technique is a tailor-made technology that can combine matrices should mimic those of the tissue ECM so that a
smart biomaterials, cells, and biomolecules to achieve this cell-favorable microenvironment can be established .
[10]
goal. For example, Schmidt et al. developed a biohybrid Moreover, hyperplasia and mechanical-failure can be
sperm micromotor (Spermbot) as a novel targeted drug initiated by the unmatched mechanical properties between
delivery system for the treatment of diseases within the implants and soft or hard tissues [142] . Hence, key material

Volume 9 Issue 1 (2023) 247 https://doi.org/10.18063/ijb.v9i1.638