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

study revealed that 3D printing was utilized to ameliorate chemical heterogeneity was explored (Figure 8C). Oxygen
the efficacy of conventional shapes, which were used in dynamics resulting from respiration and photosynthesis
drug administration by controlling the geometric criteria could be captured, and the metabolic activity of different
(Figure 7C). Due to the responsiveness of the printed bioink, cell types could be distinguished within the engineered 3D
drug release in oral delivery systems can be manipulated structures (Figure 8D). Based on these results, the authors
according to variations in the pH of the system. Melocchi stated that the suggested bioinks with sensor nanoparticles
et al. [121] fabricated a device for intravenous drug delivery. enabled non-invasive monitoring of cell metabolism and
Engineered SMHs were used to maintain a temporal form spatiotemporal dynamics in 3D-bioprinted structures. This
for bladder administration. As the device contacted water major advantage facilitates swift evaluations of cell activities
in the bladder, it reverted to its original shape (Figure 7D). in bioprinted constructs without post-processing, including
Increased treatment time was able to improve the efficiency a function of structural complexity, metabolic interactions,
of treatment by facilitating localized and extended and response to external incubation conditions. This is the
drug delivery. Next, Ceylan et al. [122] investigated the first attempt to combine a 3D bioprinting technique with a
degradation properties of gelatin methacryloyl bioink to luminescent sensor nanoparticle. In another example, Iversen
manufacture a biodegradable microrobot for the detection et al. [124] suggested a wearable, flexible smart patch through
of the matrix metalloproteinase 2 (MMP-2) enzyme. Their 3D printing acting as a pH and hydration sensor for wound
findings showed that MMP-2 could entirely degrade the healing. Wound healing is a complex biological regeneration
microswimmer after 118 h to solubilize non-toxic materials process with the physical-chemical microenvironments [125] .
(Figure 7E). After the injection of microswimmers into Therefore, real-time monitoring would offer strong benefits,
the tumor, an external magnetic field allowed the remote particularly for bedridden patients. Their study reported
control to reach a targeted location (Figure 7F). During the low-cost, flexible, and printed sensors that can be attached
process of tissue remodeling, MMP-2 destroyed collagen to the skin for the measurement of pH change and fluid
matrix and formed the structure. Taken together, these contents in a wound. The components of the printed patch
findings show that stimuli-responsive bioinks can be are shown in Figure 8E; specifically, components 1, 2, 3, 4,
utilized to create 3D engineered structures with localization and 6 were printed, and components 5, 7, and 8 were then
and control over drug release. used to conduct the measurements without interfering with
the printed parts. Eventually, a sensor consisting of different
4.3. Biosensors electrodes was printed on a polydimethylsiloxane substrate

Due to the increasing interest in precision medicine to sense pH and moisture (Figure 8F). For the pH sensor,
and personalized therapy, studies on 3D bioprinting of patches were submerged in a buffer solution, and changes
living cells have focused on the real-time monitoring of in resistance were detected with a digital Keithley model
cell growth in bioprinted structures after implantation. 2110. Afterward, the sensor output was recorded using
Trampe et al. [123] formulated a functionalized smart Kickstart (version 2.4). The printed patch was maintained in
hydrogel with luminescent optical sensor nanoparticles for buffer solution until the detected resistance was in a steady
use in combination with 3D bioprinting (Figure 8A). They state. In addition, the repeatability of the printed sensor was
developed a novel functionalized bioink incorporated investigated with time. The maximum difference between
sensor that enabled spatiotemporal mapping of oxygen the first maximum and minimum resistance values was 0.9.
dynamics in 3D-bioprinted constructs with living cells. With the fabricated hydration sensors, the hydration (or
Oxygen is a key element for the survival of encapsulated fluid) level could be measured with respect to the measured
cells and a crucial indicator to determine metabolic activity, resistance of the sensor ranging from 0% to 100%. The
which is the most important for tissue functionalities. developed sensor patch had included a sensitivity in wound
After printing was completed, the oxygen level in the pH levels of 7.1 ohm/pH. In addition, the results of the
printed construct was measured using a ratiometric RGB fabricated hydration sensor demonstrated that the moisture
camera system. Specifically, sensor particles were excited levels could be evaluated on a semi-porous surface based on
using a 445 nm customized LEP chip equipped with a the change in resistance.
bandpass filter. The combination of sensing nanoparticles
with green microalgae did not impair the viability of stem 5. Advantages and considerations of
cells (Figure 8B). Moreover, the rheological properties 3D-printed and 3D-bioprinted smart
of the bioink enabled layer-by-layer 3D bioprinting of constructs
the developed sensing bioink with a smart response to
oxygen concentration. Using the printed bioink with 5.1. Advantages over other manufacturing techniques
microalgae and oxygen sensor nanoparticles, the ability Smart constructs are considered next-generation tools in
to use luminescence imaging to map the spatiotemporal precision medicine because they can responsively perform

Volume 9 Issue 1 (2023) 245 https://doi.org/10.18063/ijb.v9i1.638