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International Journal of Bioprinting Attractiveness of 4D printing in medical field
each of these kinds of materials, for example, in terms maximum percentage of recovery for PLA was increased.
of the first three categories; according to the authors, the Conversely, increasing the thickness of the sample showed
most predominantly researched temperature-responsive a negative effect on shape recovery . On the other hand,
[44]
materials are poly(N-isopropylacrylamide) (PNIPAM)- Pieri et al. (2023) studied the degree to which the printing
based polymers since they have a relatively low critical process parameters (of an extrusion-based process), such as
solution temperature (LCST) of ≈32°C; while for pH- temperature, extrusion rate multiplier, and fiber orientation,
responsive materials, alginate has an important role in affect the shape-memory properties of an SMP, and their
3D bioprinting and consequently exhibits an attractive effect on shape memory fixing and recovery ratios was
potential to be used in 4D bioinks; and for moisture- evaluated. The results demonstrated that fiber orientation
responsive materials, cellulose fibrils embedded in a soft has a significant impact on the fixing ratio and the recovery
acrylamide matrix to print composite hydrogels with high ratio, whereas temperature and extrusion rate multiplier
swelling capacity have been studied . have almost no effect on these properties. Also, a cell
[16]
Regarding specific contributions, by combining viability assay was realized on 3D-printed samples with
biocompatible hydrogels and magneto-reactive materials, varying temperatures and extrusion rate multiplier; the
Simińska-Stanny et al. (2022) have recently produced soft results showed that a reduction in extrusion rate multiplier
actuators printed by multimaterial direct ink printing increased cell viability and that fiber orientation impacted
(4D printing) . Non-cytotoxic and biocompatible shape memory functionality. This study can provide
[41]
[45]
bionanocomposites were studied for biomedical insights on optimizing biomedical applications . Solis
applications. Hydrogel structures were printed using a BioX and Czekanski (2022) investigated the effect of the printing
3D printer (CELLINK, Sweden). The author’s proposal temperature on PNIPAM hydrogel properties manufactured
[46]
involves the combination of magnetically responsive using DLP . When the printing temperature varied
hydrogel materials with programmable patterning to meet between 5, 10, and 15°C, the results showed that increasing
biocompatibility and functionality requirements of future the temperature by 10°C caused a reduction in 50% in the
soft robotics for medicine and biomedical engineering maximum swelling capacity, almost a 10% increase in water
applications . On the other hand, a cellulose–hydrogel retention, and a 6.5°C variation in the low critical solution
[41]
composite ink for 4D printing applications was developed temperature. The second trend concerns the development of
[46]
by Mulakkal et al. (2018) . They created an ink formulation cell-friendly bioprinting methods . Stroganov et al. (2018)
[42]
through a 3D extrusion process using a commercially proposed an innovative approach for 4D biofabrication of
available Prusa Mk2, and a petal architecture was chosen 3D cellular structures using thermosensitive shape-changing
to analyze the 3D printing capabilities and subsequent polymer films with a photolithographically patterned
4D morphing of the designed cellulose formulations. surface that is able to selectively absorb cells in specific
They claimed that a sustainable and cost-effective ink was regions. This method holds the potential in bioscaffolds
[47]
produced, aiming to make 4D printing more accessible and fabrication and finds use in tissue engineering . Ding
encourage the adoption of this technology . Mathews et al. et al. (2022) presented a 4D bioprinting process that allowed
[42]
(2017) fabricated a 4D bionanoink composition containing the formation of a shape-morphing cell condensate-
monomers, crosslinker, photoinitiator, bacteriorhodopsin, laden bilayer system that had tunable deformability and
carbon nanotubes, and silver nanoparticles . The acrylic- microgel degradation, enabling controllable morphological
[43]
based composition was developed considering the same transformations and on-demand liberation of deformed
[48]
proportions of 2-hydroxyethyl methacrylate (2-HEMA) and cell condensates . Díaz-Payno et al. (2023) reported a 4D
di(ethylene glycol) dimethacrylate (dEGdMA) and 15% of bioprinting method to fabricate curved structures from
crosslinker di(trimethylolpropane) tetraacrylate (dTMP4A). hyaluronan and alginate with potential use in cartilage
[49]
A biophoton-electrochemical cell was printed by SLA using engineering . In 2020, Kim et al. proposed a cell-friendly
an Ember 3D printer with a 405-nm LED source. The result and biocompatible 4D bioprinting system based on DLP,
[50]
is a bionanoink with improved bioactivity and durability . which is applicable in tissue engineering .
[43]
Regarding the printing methods category, two trends Concerning the mathematical models category, two
were identified. The first trend involves the investigation of trends were identified. The first trend considers the use
the effect of printing parameters on printed parts. Eryildiz of theoretical-experimental approaches to predict shape
(2023) studied the effect of 4D printing parameters, such deformation. Zhao et al. (2022) applied an effective
as sample thickness, nozzle temperature, deformation method to predict the folding angle of a 3D-printed
temperature, and holding time, on the percentage of thermo-responsive hydrogel/elastomer bilayer structure
shape recovery. The results showed that by increasing the and analyzed the effect of variations in manufacturing and
[51]
deformation, holding time, and nozzle temperature, the material properties on the folding angle . This method
Volume 9 Issue 6 (2023) 192 https://doi.org/10.36922/ijb.1112

