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International Journal of Bioprinting                                           Robotic in situ bioprinting


            2. In situ bioprinting modalities                    The aforementioned methods are the most common
                                                               modalities in bioprinting. Their derivatives, which include
            2.1. Extrusion-based bioprinting                   acoustic droplet ejection , direct-write assembly , fused
                                                                                  [24]
                                                                                                      [25]
                                                                               [26]
                                                                                                   [27]
            Extrusion-based bioprinting involves the continuous   deposition modeling , and powder printing , have also
            deposition of bio-ink through syringes or nozzles to   been developed recently. These printing modalities can be
            construct 3D tissues or organs . Applied pressure,   further applied to a variety of printers (or end effectors)
                                        [21]
            piezoelectric effect, and solenoid dispensing have been   mounted  on  robotic  arms  for  dexterous  and  precision
            employed by bioprinters of this type. Extrusion-based   biofabrication.
            bioprinting generally offers gentle fabrication with high   3. Bioprinting robots
            regard for cell viability. One of the most promising features
            of this technology lies in the fact that multiple cells and   Robots and handheld devices are commonly employed to
            biocompatible materials can be simultaneously applied   achieve in situ fabrication of 3D structures with complex
                                                                                       [15]
            through different nozzles. Furthermore, it is regarded as   shapes  and curved surfaces . Robotics can  facilitate
            the most mature solution for in vivo clinical applications,   bioprinting tasks with high accuracy and automation level
            owing to its decadal recognition in arthroscopy repair.   without  exhaustion.  Robots  have  been  routinely  used  in
                                                                                             [28]
            Commercial bioprinters that are based on this technology   minimally invasive surgical settings , thereby paving
                                                                                         [29]
            have been successfully developed.                  the way for  in situ  bioprinting . Robot configurations
                                                               determine the working space, deposition flexibility, and
            2.2. Inkjet bioprinting                            operational precision of bioprinting, of which Cartesian
            In inkjet bioprinting, bio-ink is sprayed onto the deposition   coordinate, articulated, and parallel robots are the main
                                                                          [30]
            substrate via droplet or continuous ejection to establish 3D   configurations . The typical robotic-assisted bioprinting
            living constructs . Similar to traditional inkjet printing,   process is shown in Figure 2.
                         [22]
            this technology has certain merits, including a broad   3.1. Configurations
            selection of commercial apparatus due to the low cost of
            machine modification. Ease of multiple printer heads   3.1.1. Cartesian coordinate robots
            installation facilitates heterogeneous architectures of   Conventional 3D printers deposit materials layer-by-
            tissue or organ and ensures a sound printing resolution.   layer along the vertical direction (Figure 3A) using the
            An ability to keep integrity is critical as newly printed   axis-aligned  slicing  method.  A  planar  surface  is  often
            cells are expected to have long-term survival in the in vivo   needed to support the printed structure. Adopting this
            environment. A  prompt establishment of mechanical   mechanism allows for individualized modeling and
            properties  through  supporting  biomaterials  is  valuable.   rapid fabrication. The procedure involves 3D computer
            Since the printing conditions and size are limited, inkjet   model design and slicing followed by layer deposition of
            bioprinting  is  merely  practical  for  in vivo  repair  or   biomaterials through force, sound, light, electricity, and
            fabrication of exterior structures, such as skin.  heat. Extrusion-, inkjet-, and optics-based methods can
                                                               be  readily combined  with Cartesian  coordinate robots.
            2.3. Laser-assisted bioprinting
                                                               The advantages of this technology for bioprinting include
            Laser-assisted bioprinting employs a laser to polymerize   low cost, technology transferability from conventional
            bio-ink  into  solid  structures .  Laser  direct-write   3D printing, and a high degree of stiffness of the
                                      [23]
            techniques have  been  widely used in  this  approach.  By   printing platform, whereas the challenges are evident
            laser pulses, living cells are selectively transferred from   in  anisotropic  bioprinting .  Since  body  tissues  are
                                                                                      [31]
            the supply container to defect locations. Stereolithography   anisotropic, different anisotropic material properties
            can also be used for in vivo bioprinting to allow precise   along an axis are needed. Moreover, the stair-step effect is
            fabrication of structures with micro or nanoscale resolution.   non-negligible . During the fabrication of each layer, the
                                                                           [32]
            The fact that the heat generated by the laser or exposure   motion of the nozzle is restricted to a two-dimensional
            to  ultraviolet  lights  may impair  cell viability  should be   plane along the direction of gravity. This inevitably
            considered. Moreover, laser or stereolithography-based   results in the staircase effect, where surface distortion
            techniques may be unsuitable for in vivo scenarios due to   occurs between neighboring layers. To improve printing
            the machine size. Although the advantage of optics-assisted   flexibility, Edward Shi et al. proposed a method combining
            bioprinting in ultrahigh resolution and precision to meet   Cartesian and curvilinear printing head motion for  in
            the requirements of clinical settings, there is still room for   vivo bioprinting. A biomimetic “tendon cable” soft robot
            improvement in terms of photocrosslinkable biomaterials   arm was added to a conventional Cartesian three-axis
            and photonics techniques.                          3D printer to facilitate motion along six independent


            Volume 9 Issue 1 (2023)                        100                      https://doi.org/10.18063/ijb.v9i1.629
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