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3D Printing of hydrogel composite systems: Recent advances in technology for tissue engineering

           microdots. The thickness of microstrand can be controlled   spreading during extrusion.
           by the viscosity of hydrogel, deposition rate, diameter   2.2.3 Pressure-assisted Microsyringe (PAM)
           of nozzle, and applied pressure. The material dispensing
           head generally moves in x, y, z directions, while the build   The PAM technique, similar to FDM without heating
                                                                                                 [46]
           platform is kept in place. Liquid flow is generated by   system is first proposed by Vozzi in 2002 . In the initial
           working stepper motor (volume-driven injection nozzle)   stage, pneumatic driven glass capillary microsyringe which
           or filtered air pressure (pneumatic nozzle). The key point   moves in the vertical plane was used to deposit materials
           of this technique is to plot hydrogel into a liquid solution   on a substrate. Vozzi and his research group modified PAM
                                                                                              [47]
           with a carefully designed density that matches that of the   systems for hydrogel microfabrication . Compressed air
           hydrogel.                                           and pneumatic driven microsyringe were replaced with a
            Various materials can be used in 3D plotting system such   stepper motor and piston assisted microsyringe, respectively.
           as hydrogels, nanocomposite hydrogels, polymer sol, and   Moreover,a temperature controlled syringe module with an
           bioactive polymers such as proteins [39–42] . Materials with   aluminum jacket was added to control the temperature of
           low viscosity can also be used in plotting since deposition   deposit materials.
           takes place in a liquid medium with a matching density.   2.2.4 Low-temperature Deposition and Manufacturing
           Moreover, thermal sensitive biocomponents such as growth   (LDM)
           factor and even cells can be incorportated into hydrogels
           because heating is not required. Extruded hydrogels can be   Xiong et al. designed LDM systems to overcome heating
                                                                     [48]
           cured by plotting in a reactive solution or by using mixing   process  . In this technique, temperature is decreased
           nozzles with multiple dispensing component. However,   to solidify materials. Materials such as hydrogels are
           the microstrands of scaffolds constructed by 3D plotting   embedded in feeder connected to a screw pump nozzle
           technique normally possess smooth surfaces, which cause   and injected from the nozzle that can move along
           unfavorable environment for initial cell adhesion. Thus   the XY axis onto a building stage at a temperature
           additional surface treatment has been researched for   below 0 °C. Printed scaffolds are necessary to undergo
           fabricating the favorable surface with modified initial cell   freeze-drying process to remove the solvent. Modified
                  [43]
           adhesion .                                          LDM technique, called multinozzle low-temperature
                                                               deposition and manufacturing (M-LDM) was developed
           2.2.2 Direct Ink Writing (DIW)                      by incorporating multiple nozzles with different types
           Direct ink writing (DIW) or direct write assembly (DWA)   [49] . They are used for fabrication of scaffolds with
           was first investigated by Lewis et al. [44]  A variety of inks   gradient structures and materials by the incorporation of
           such as hydrogels, nanoparticle filled inks, colloidal   additional jetting nozzles into the LDM process.
           suspensions and gels, and organic inks can be printed in   2.2.5 Robocasting
           2D and 3D patterns with feature sizes ranging from 100
           nm to 1000 μm. Components of DIW apparatus are the   Robocasting is also a nozzle based process which was
           three-axis translation platform, compressed air supply,   originally adapted to produce ceramic scaffold using
                                                                                       [50]
           cylindrical nozzle, and optical microscope for real-time   highly loaded ceramic slurries . The system is composed
           monitoring. The hydrogels are stored in each orifice   of stationary dispensing head and movable platform that
           mounted on the Z direction motion stage and printed   can move in X, Y and Z axis. The slurry injected layer by
           through a nozzle onto a moving XY stage. The pressure   layer from a syringe has to sustain their weight and the
           of orifice and printing speed depend on nozzle diameter   weight of next layers to sustain the printed features. Thus,
           and rheology of hydrogel, respectively.             low viscous slurry or hydrogel alone are inadequate for
            There are two important considerations regarding   robocasting technique. Recently, hydrogels were applied
           the hydrogels used in DIW technique. First, they must   as carriers for ceramic powder in this system. Although the
           obtain self-supporting ability and spanning shapes   final product is a ceramic scaffold that is formed through
           with controlled viscoelastic characteristics. Therefore,   burning out hydrogels, this result indicates the great
           extruded hydrogels should set instantly to enable   potential of robocasting process in fabrication of hydrogel-
                                                               based composites.
           feature retention of the printed structures. Second, high
           concentration of nanoparticle or colloid in hydrogels is   2.2.6 Other Apparatus
           preferred to reduce shrinkage during the drying process   Nozzle-based 3D printing process is a promising technique
           of the completed assembly. Generally, 70–85 wt% of   to fabricate hydrogel-based composite scaffolds due to its
           solid loadings in hydrogels are preferred for assembling   versatility in various printing conditions. This technique is
           planar and spanning filaments [45] . The nanoparticle or   capable of printing large porous structures for infiltrating
           colloid network in hydrogels is able to resist compression   body fluid and controlling mechanical and biological
           stress caused by capillary tension, thereby preventing   properties, which cannot be carried out by other hydrogel


           6                           International Journal of Bioprinting (2018)–Volume 4, Issue 1
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