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


            relevant fields have spawned various 3D printing techniques   (e.g., irradiation intensity, light penetration, and
            with unique working mechanisms. As defined in the ASTM   polymerization), functional additives, such as magnetic
            F2792 standard, AM techniques are divided into seven   particles, conductive compounds, biochemical reagents,
            categories:  Binder  jetting,  directed  energy  deposition,   and chromogenic payloads, can be flexibly incorporated
            material extrusion, material jetting, powder bed fusion,   into constructs, which further expand environment-
            sheet lamination, and vat photopolymerization . This   responsive intelligence.
                                                   [21]
            section focuses on relevant techniques frequently applied   Because of the advantage for shaping materials
            to  precision medicine  and discusses  their  principles,   with high resolution and complex architectures, these
            benefits, and limitations, as well as the materials used in   techniques are useful for constructing ultrafine and
            each technique.                                    delicate smart biomedical devices, such as microneedles
            2.2.1. Stereolithography                           and micro-/nano-biorobots. In combination with
                                                               programmed dynamic changes, these devices are equipped
            Stereolithography (SLA) was the first 3D printing   with advanced performances. For instance, relying on
            technique developed and was patented by Charles Hulk   intensity decays as light penetrates the resin precursor
            in  1986 .  As SLA  is  a typical  technique  based  on vat   solution during a DLP process, a microneedle arrays with
                  [22]
            photopolymerization, the exposed photocurable resins   back-facing barbs can be created through the desolvation-
            used in this technique are selectively polymerized through   induced deformation of multiple horizontal struts
            several  types  of  resin  chemical  reactions  (e.g.,  free   (100 μm thickness and 450 μm length) on microneedles
            radical, methacrylate, and cationic reactions) under light   as a post-printing procedure, which enhances the tissue
            irradiation. By sketching the profile of each layer using   adhesion effect by 18 times compared with those of barb-
            ultraviolet (UV), infrared, or visible lasers, a solid slice of   free products . As another representative example,
                                                                          [28]
            a 3D object can be generated. The vertical movement of   micro-/nano-biorobots with exquisite designs can be easily
            the working platform at a certain distance induces the flow   constructed through polymerization-based 3D printing
            of liquid resins to form another “blank paper” for printing   techniques . When propelled in response to physical or
                                                                       [29]
            the  next  layer   (Figure  3A(i)).  Due  to  the  precision  of   chemical stimuli, these biorobots may complete various
                       [23]
            computer-controlled laser beams, complex geometries and   medical tasks (e.g., cancer therapy, targeted drug delivery,
            submicron printing resolutions can be obtained . The   track imaging, and microsurgery).
                                                    [24]
            emergence of two photon polymerization (TPP) technique
            further refines the printing resolution down to nanometer   2.2.2. Selective laser sintering (SLS)
            scale. However, the point-by-point scanning of laser beams   As  shown  in  Figure  3B,  SLS  is a  powder  bed  fusion
            substantially limits the printing efficiency of early SLA.  technique in which a laser beam is used on the surface

              To accelerate the fabrication speed, digital light   of a thermoplastic powder to produce a designed image.
            processing (DLP) introduced a digital projector consisting   The powder is then recovered from the surface, and
            of micro-mirror arrays to flash an image of a layer across the   the  procedure  is  repeated. The  laser  produces  a  high
            entire platform, curing all the targeted resin simultaneously   temperature  and  selectively  melts  the  powder  such  that
            (Figure 3A(ii)) . This improvement converts the scanning   the scaffold structure has low porosity. Modulating the
                       [25]
            manner from point-by-point to layer-by-layer, facilitating   laser power and scanning speed can result in different
            the efficient printing of 3D constructs. Kelly  et al.    phenomena. Decreasing the laser scanning speed could
                                                        [26]
            reported a volumetric additive manufacturing approach   result in a dense structure because the powder is exposed to
            (VAM) by rotating a photopolymer in  a dynamically   the laser beam for longer duration; however, the fabricated
            evolving light field, allowing for the printing of an entire   structure would be more imprecise. Increasing the laser
            complex structure through a complete revolution, skipping   scanning speed could result in a porous structure because
            the need for layering (Figure  3A(iii)). Using this novel   the powder absorbs less laser power .
                                                                                           [30]
            technique, several centimeter-scale objects can be printed   Many types of materials can be used in SLS. Thermoplastic
            in seconds.                                        polymers, including natural and synthesized polymers,
              With this working principle, the materials applicable   such as cellulose  and polycaprolactone (PCL) , have
                                                                             [31]
                                                                                                      [32]
            to photopolymerization-based 3D printing techniques   been used to manufacture scaffolds. Bioactive glass,
            are generally compatible to photocurable materials,   ceramics, and metals can be used in SLS. Because polymers
            enabling a wide range of materials to be adoptable for   possess elasticity  and low  stiffness and  ceramics  have  a
            engineering smart structures, including hydrogels, shape-  greater stiffness than polymers, mixing polymers and
            memory polymers, and liquid crystal elastomers .   ceramics (e.g., PCL and hydroxyapatite [HA]) can improve
                                                        [27]
            Without impeding key parameters in a printing procedure   the mechanical properties of the structure . The SLS
                                                                                                   [33]
            Volume 9 Issue 1 (2023)                        233                      https://doi.org/10.18063/ijb.v9i1.638
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