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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
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