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International Journal of Bioprinting                          Unique characteristics of 3D-printed microneedles




            the cutting speed may be slow. In comparison, laser   thinning ink ensures smooth flow during extrusion and
            ablation directly burns the substrate material with a laser   solid-like behavior post-extrusion. It is worth noting
            (e.g., CO  laser) in order to carve the desired structure.   that the precision of extrusion-based 3D printing is
                   2
            However, when dealing with polymers with low melting   relatively  low,  making  it  challenging  to  directly  print
            point, thermal defects, such as scorching, re-curing, and   sharp microneedles.
            shrinkage, may occur.  Representative works for each type   Recently, researchers have used extrusion-based printers
                             22
            fabrication method are summarized in Table 1.      to directly print drug-loaded microneedles. Researchers
            2.2. 3D printing methods for                       have also combined FDM with etching to enhance the
            microneedle manufacturing                          3D printing resolution, achieving a microneedle diameter
            According to the American Society for Testing and   of 100 μm. The mechanical properties and characteristic
            Materials (ASTM) standards, 3D printing technology   dimensions of the microneedles were further improved
            can be divided into seven categories. Among them,   by replacing the photopolymer with materials with
                                                                                                  65
            the  technologies  suitable  for  microneedle  fabrication   higher hardness 49,63,64  (Figure 3A). Wu et al.  used a dual-
            include  material  extrusion, vat photopolymerization,   nozzle Allevi 2 bioprinter to create microneedles with
            and powder bed fusion. Table 2 provides an overview of   a tip diameter of approximately 20 μm (Figure 3B). By
            the characteristics of these 3D printing technologies and   mixing the ink with the drug, they were able to bypass the
            the types of microneedles they can directly manufacture.    secondary drug loading step, but with lower precision. In a
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            Table 3 summarizes the microneedle performance achieved   recent report,  DIW was successfully used to manufacture
            by different 3D printing technologies.             double-layer microneedles with water-soluble bases and
                                                               drug-loaded top layers. The yield strength of the material
            2.2.1. Extrusion-based 3D printing                 was enhanced with added nanosilica particles, which
            Extrusion-based  3D  printing,  which  includes  fused   significantly improved the printing precision by about two
            deposition molding (FDM) and direct ink writing (DIW),   orders of magnitude.
            is a common method of manufacturing microneedles.
            FDM prints the model by heating thermoplastic filaments   2.2.2. Vat photopolymerization
            and extruding them from a movable nozzle. DIW      Vat photopolymerization (VP) creates 3D objects by
            extrudes viscoelastic ink from a nozzle, and the shear-  solidifying photosensitive resins layer by layer with a light


            Table 1. Summary of traditional microneedle manufacturing methods

             Fabrication methods                   Materials         Pros                Cons
             Indirect fabrication  Direct molding  Polymer, hydrogel,  Simple operation, low cost,   Complex structures and
                                                   ceramics, water 15,23,24  high precision, and reusable  material limitations; structure
                            Reverse molding                          molds 25            is easily damaged 26
             Direct fabrication  Microfabrication  Silicon, metal 27  Easy to control etching   High cost and low speed 30
                            (dry etching)                            direction, high precision
                                                                     (compared with wet
                                                                     etching) 28,29
                            Microfabrication       Silicon, metal 31  Fast speed and low cost   Difficulty in
                            (wet etching)                            (compared with dry   manufacturing complex
                                                                     etching) 32         structures and low precision 32
                            Microfabrication       SU-8, PMMA 33,34  Expected to have low mass   Limitations in material, harsh
                            (photolithography)                       production costs 35  processing conditions 36
                            Microfabrication       Biodegradable polymers,  Super sharp needle tip, fast   Many influencing factors
                            (thermal drawing)      metal 37,38       speed and can be fabricated   (temperature, motion), poor
                                                                     on curved surfaces 39  uniformity 40
                            Laser machining (laser cutting)  Silicon   Have great potential in   Limitations in material, slow
                                                   (stainless        terms of mass productivity   speed 43
                                                   steel), polymer 41  and economy, sharp needle
                                                                     tips 42
                            Laser machining (laser ablation)  Poly-lactic acid 44  Easy to operate with high   Limitations in materials 43
                                                                     accuracy, low cost 22
            Abbreviations: SU-8, submicron photoresist; PMMA, poly(methylmethacrylate).


            Volume 10 Issue 4 (2024)                        64                                doi: 10.36922/ijb.1896
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