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International Journal of Bioprinting                       3D-printed nanocomposites: Synthesis & applications




            substrate stiffness in some representative tissues has been   provide finer control over filler alignment than those with
            investigated.  Therefore, by controlling the alignment   single-material extrusion capability. By extruding multiple
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            of AFs, the scaffold exhibits anisotropic mechanical   materials at once, each with its own unique properties,
            properties, thus regulating cellular behaviors. For instance,   scientists may design structures with precisely controlled
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            human umbilical vein endothelial cells (HUVECs) are   filler orientation.  This method is perfect for fabricating
            found  to align themselves  along  the  direction of  fibers.   composite tissues and scaffolds with tailored architectural
            Additionally,  aligning  the  conductive  fillers  increases   properties. In smart rheological control, the viscosity and
            the possibility of filler connections, which help establish   shear-thinning behavior of the bioink are adjusted for
            conductive network and promote cell growth in scaffolds,   optimal performance. By fine-tuning these characteristics,
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            such as cardiac tissues.                           we can improve the bioink’s ability to aid with filler
                                                               alignment during printing. Rheological optimization
               Filler alignment is a complex problem warranting a   keeps the filler oriented while the bioink flows smoothly.
            solution by means of novel technical approaches. There
            are a number of intriguing approaches for achieving exact   Filler alignment can be stabilized through post-printing
            filler orientation, including the use of external stimuli like   crosslinking techniques. After bioprinting, the structure
            magnetic and electric fields, the optimization of nozzle   can be treated with UV radiation, chemical crosslinkers,
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            design, gradient printing, and multimaterial extrusion.   or enzymatic reactions.  The fillers can be permanently
            Researchers can use external magnetic fields to precisely   fixed in their preferred orientation using any one of these
            move and align fillers in bioink that contains magnetic   treatments to enhance the structure’s durability.
            nanomaterials.  This method provides interesting new   The combination of smart rheological control, real-
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            opportunities for the printing of highly shaped tissues   time monitoring, and post-printing crosslinking has
            by allowing for dynamic control over filler orientation   placed us closer to realizing the full potential of bioprinting
            both during and after the printing process. Pardo et al.   in regenerative medicine and tissue engineering. However,
            suggested that magnetically assisted 3D bioprinting and   recreating the organization of ECM and the cell patterns
            matrix-assisted 3D bioprinting be used together to make   of anisotropic tissues in bioengineered constructs is still a
            high-resolution hybrid composites that can not only copy   major problem in the realm of biofabrication.
            the anisotropy of native tissues but also allow for remote
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            control of tissue constructs as they mature.  For this   6. Applications of 3D-printed polymer
            purpose, bioinks made of gelatin-methacryloyl (GelMA),   composites for biomedical applications
            short magnetically responsive microfibers (sMRFs), and
            human adipose-derived stem cells (hASCs) were extruded   To demonstrate the applicability of bioprinting in tissue
            into  fibrillar  cellulose  nanocrystals  (CNCs)-based  baths   engineering, most studies focused on developing bioink
            while low-strength magnetic fields were applied. This   materials because cell-friendly environment is one of the
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            produced high-resolution constructs with controlled   most important factors influencing its feasibility.
            anisotropic architectures.                         Additionally, AF-PNCs are under investigation as the
                                                               orientation of the AF has significant influence on the
               In the quest for filler alignment, electric fields are   cellular behaviors.
            another potent instrument. Electrostatic forces can be used
            to  direct  and  orient  charged  fillers  within  the  bioink.    6.1. Skin tissue
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            It is feasible to engineer tissues with desired qualities by   Skin is the largest organ of human body and composed of
            aligning charged fillers to form structures using controlled   multilayered structures, including epidermis, dermis, and
            electric fields. Moreover, shear forces within the printing   hypodermis, and various cell types, such as keratinocytes,
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            nozzle can be manipulated to achieve filler alignment.   fibroblasts, and melanocytes.  Artificial skins can not
            With optimized nozzle design, bioprinters may generate   only serve as skin grafts for wound healing but also
            controlled shear pressures on the bioink during extrusion.    experimental platform to investigate its permeability
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            Mechanically enforcing filler alignment along the shear   and inflammatory response during the transdermal and
            direction paves the way for highly anisotropic design. By   topical drug formulation development and screening.
            adjusting the filler content or bioink properties, gradient   The development of techniques has allowed for the highly
            printing is a flexible method. Fillers position themselves as   accurate and complex 3D bioprinting of multistratified
            bioink moves from one area to another, creating structures   skin tissue that closely resembles natural skin.
            with acceptable orientation gradients. This method is   Cubo et al. fabricated a human plasma-derived bi-
            applicable to the development of multilayered, complex   layered skin.  To replicate the structure of natural skin,
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            tissues.  Bioprinters with dual or multinozzle systems   they printed the dermis with fibroblasts-laden fibrin
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            Volume 10 Issue 2 (2024)                        89                                doi: 10.36922/ijb.1637
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