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Materials Science in Additive Manufacturing                      From 3D printed molds to bioprinted scaffolds


            NH  (IZZK) peptide bioinks for bioprinting applications   suction force-driven, high-velocity flow of the hydrogel
               2
            have been reported . These peptides have been rationally   prepolymer that backs up the continuous replenishment
                           [17]
            designed as ultrashort and self-assembling are considered to   of the prepolymer solution below the curing part and
            be an encouraging class of biomaterials as they address several   the nonstop part growth. The process is unique for the
            limitations that are affiliated with bioinks . Amphiphilic   hydrogel prepolymer without externally supplemented
                                             [18]
            peptides are composed of 3 – 7 amino acids in length and   oxygen. The rapid printing of centimeter-sized hydrogel
            they self-assemble under physiological conditions to form   models using FLOAT has exhibited a significant reduction
            hydrogels from nanofibers that meticulously resemble fibers   in deformation and cellular injury caused by prolonged
            within the extracellular matrix. The characteristics previously   exposure to environmental stresses in layer-by-layer-based
            mentioned make ultrashort peptides a suitable biomaterial for   printing methods.
            regenerative medicine applications and tissue engineering .
                                                        [19]
            Susapto  et al. have demonstrated the excellent tunable   Meanwhile, the additional degrees of freedom of robots
            mechanical properties of their bioinks, thus making them   have increased the capability, quality, and productivity of
                                                                                    [25]
            suitable as robust bioinks for 3D bioprinting . These bioinks   traditional 3D fabrication . One of the major issues in
                                             [17]
            avoid cell compromising abrasive conditions like chemical   conventional additive manufacturing addressed by Bhatt
            treatments or ultraviolet (UV) cross-linking during the printing   et  al. is that printing structural layers perpendicularly
                                                                                                     [26]
            process. Their peptide bioinks verified an instantly solidifying   limits the types of geometry that can be printed . Robot-
            cell-embedding 3D bioprinting process under physiological   assisted additive manufacturing allows for change of
            conditions at a low, cost-effective bioink concentration. These   directions during 3D fabrication, thus making fabrication
                                                                                       [27]
            peptide bioinks are capable of being considered superior   of complex geometry feasible . A  study by Song  et  al.
            due to their biocompatible, body-like, synthetic nature, and   concluded that printing in tilted orientations can help avoid
            support of an automated cell printing process.     the staircase effect that occurs due to the approximation of
                                                               planar layers for highly curved geometry . Moreover, a
                                                                                                 [28]
              The main classification of hydrogels is based on their   3D printing robot can decrease or eliminate, in some cases,
            sources - natural, synthetic, and hybrid. Natural hydrogels   the need for support structures due to its ability to orient
            can be obtained from proteins (elastin, collagen, fibrin, silk   the printing tool to reach the objects from different angles.
            fibroin, and gelatin), polysaccharides, and decellularized   In other words, the tool path of the deposition head can
            tissues . Synthetic hydrogels display more versatile and   be non-planar in space . This survey paper, Bhatt et al.,
                 [20]
                                                                                  [26]
            easily  controlled  physical  and chemical  properties  when   also mentioned two other advantages of utilizing robots
            compared to natural-origin hydrogels . Hybrid hydrogels,   as 3D printers in manufacturing which are scalability and
                                         [21]
            on the other hand, are a mixture of natural and synthetic   mobility of the printed structures . For instance, a recent
                                                                                         [26]
            hydrogels, which incorporate structures with desirable   study highlights the application of additive manufacturing
            characteristics . Hydrogels can also be classified by their   in the fabrication of lateral flow assays for the rapid in-field
                       [22]
            structural integrity (durable and biodegradable). Durable   detection of COVID-19 .
                                                                                  [29]
            hydrogels are mostly synthetic and mechanically stronger
            in comparison to hydrogels of natural origin, while   In this study, we combined the advancing technologies
            biodegradable hydrogels are natural polymers, commonly   of  additive  manufacturing,  3D  biofabrication,  and
            non-toxic, and demonstrate minimal adverse effects   robotics to develop a hybrid fabrication approach for
            compared to synthetic alternatives . For the hydrogels to   high-quality printing of cellular bio-scaffolds with
                                       [23]
            function properly, they are expected to meet several design   soft  bioinks (Figure  1).  We  offer  a multi-step method
            criteria so that they can stimulate new tissue formation and   involving SLA and extrusion-based printing technologies
            induce minimal to no immune reaction from the recipient.   to precisely engineer customizable mold support
            The selection of these hydrogels depends primarily   structures to improve printing resolution and mechanical
            on their physical parameters (mechanical properties,   fidelity. Our process is implemented by 3D bioprinting a
            biodegradability or bioresorbability, porosity, and   human ear model with peptide-based bioink embedded
            swelling) and biological performance (biocompatibility,   with MSCs and assessing the 3D scaffold for mechanical
            cell adhesion, vascularization, and bioactivity) .  fidelity and cell viability.
                                                 [20]
              On the other  hand, a fast hydrogel projection   2. Method
            stereolithography (SLA) technology (FLOAT), which
            allows the fabrication of centimeter-sized and multi-  We proposed a hybrid fabrication approach to enable 3D
            scale solid hydrogel models in minutes has been    bioprinting using soft bioink materials, such as peptide
            reported . This was achieved by precisely controlling   hydrogels, for the printing of complex organ and tissue
                   [24]
            the photopolymerization condition and establishing low   structures. The hybrid approach involves a multi-step “3D

            Volume 1 Issue 1 (2022)                         3                      https://doi.org/10.18063/msam.v1i1.7
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