Page 248 - IJB-9-1

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

electrical stimulation. These results could influence stem widely used for designing light-responsive structures
cell differentiation and functionalities. that regulate the extracellular environment . The use
[97]
Electrically responsive biomaterials have recently of light-responsive graphene-based materials has also
[98]
been shown to be capable of drug release with electrical been reported . A polydopamine-functionalized GO
signals triggering rapid, localized, responsive, and nanosheet (GO-PDA) was used to fabricate the micro
controllable drug release . This facilitates localized burst pattern. The GO-PDA structure transformed to form a box
[85]
release, which is appropriate for long-term implants. after 2.6 seconds of near-infrared (NIR) light exposure.
Several growth factors and drugs are accommodated into A microbot and an artificial hand were also assembled.
conductive polymers for controlled release, including The artificial hand could fold and grasp an object when
dopamine , naproxen , heparin , nerve growth factor stimulated by NIR light, whereas the microbot moved
[87]
[88]
[86]
(NGF) , and dexamethasone . Specifically, drug release forward upon the NIR stimulation and showed precise
[90]
[89]
can be controlled stepwise, and payload volume can be remote control.
controlled through electrical stimulation by modifying the In addition to mechanical changes, light-responsive
electric potential used. Although controlled drug release biomaterial inks can control the patterning of biochemical
for cell manipulation within 3D structures has not been signals and define signaling areas that affect cell behavior or
widely studied, electrical stimulation and drug release cell fate . Biomaterial inks can be considered to respond
[99]
have been shown to have remarkable effects on neuronal to two-photon excitation by employing NIR light [100] . Using
cell development and growth. An electroactive structure a PEG hydrogel cross-linked with allyl sulfide groups,
capable of controlled release of BMP4 has also been shown Gandavarapuet et al. [101] reported a ligand attachment and
in a rabbit model with electrodes inserted into the bone subsequent patterning within a 3D structure through two
defects. Enhanced bone healing in the tested animals was photons. This technique formed an RGD peptide pattern,
demonstrated with the synergistic benefits of electrical and the results demonstrated the selective attachment of
stimulation and drug release. human mesenchymal stem cells (hMSCs) to the patterned
region. Similarly, Wylie et al. [102] showed the patterning
3.4. Light-responsive biomaterials
of multiple growth factors within 3D biomaterial inks
Light is a versatile stimuli for the control of engineered through the two photons. A coumarin-photocaged thiols-
structures due to the easiness of use . Optical stimuli included agarose was activated through the reaction
[82]
were used to a localized region with a high spatial of photon with the two distinct maleimide-conjugated
resolution. The light intensity can affect the behavior of linkers. It eventually allowed the independently controlled
biomaterial inks mainly by manipulating the polymer immobilization of two stem cell differentiation factors.
chains. Light-responsive biomaterials are an emerging Light-responsive biomaterials can also be used to time the
class of materials for biomedical engineering applications, presentation of bioactive cues [103] . Kloxin et al. designed a
including photothermal and photodynamic therapy , platform with a time-controlled presentation of adhesive
[92]
[91]
drug delivery , and regenerative medicine . peptides and photo-controlled degradation. An RGD
[94]
[93]
Light-responsive biomaterials not only enable adhesive peptide linked to a PEG-based structure was
spatiotemporal tunability of biomaterial ink but also incorporated using a nitrobenzyl ether-derived photolabile
provide biological cues that significantly affect cellular tether. Photocleavage of RGDs from the structure on
function and behavior. For instance, the mechanical day 10 after the culture increased the production of
property of the biomaterial ink has a part in tumor cell glycosaminoglycan and induced the differentiation of
migration since ECM stiffness is related with cellular hMSCs through a chondrogenic pathway with their
[95]
invasion and cell phenotype. Since these processes take a viability retained during the culture.
long time to complete, a dynamic change of the stiffness 3.5. Ultrasound stimulation
by an external source is required. Lee et al. presented a
[96]
novel method to manipulate cell adhesion through light- Ultrasound pressure waves at frequencies above 20 kHz are
[82]
triggered activation of RGD peptide. Growth factors that used as controllable remote stimuli for 3D structures .
are delivered by light-responsive nanoparticles through The pressure caused by oscillation and the resultant
a biomaterial ink could also promote cell function and mechanical effects have been widely used in various tissue
activity. Therefore, recent achievements in the study of engineering applications, including controlling the release
novel applications of light-responsive biomaterial inks from acoustically responsive carriers, enhancing the
in 3D cell culture hold great promise for future clinical transdermal permeability of agents through sonophoresis,
applications. Carbon nanotube (CNT), gold nanoparticles, and manipulating cells in vitro into defined geometric
graphene oxide (GO), and graphite carbon nitride are assemblies. Ultrasound waves are readily penetrated

Volume 9 Issue 1 (2023) 240 https://doi.org/10.18063/ijb.v9i1.638