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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

