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Materials Science in Additive Manufacturing                             3D-printed nozzle for 3D bioprinting



            eco-friendly coral restoration [5-7] . One of the main branches   low-viscosity bioinks to reduce shear force in the nozzle
            of 3D printing technology is 3D bioprinting, which fabricates   and eliminate post-printing crosslinking procedures. For
            cell-based tissue constructs for tissue  engineering  and   instance, several low-viscosity bioinks for 3D bioprinting
            regenerative medicine . 3D bioprinting is revolutionizing   and cell culture have been developed [19,20] . Incorporating
                             [8]
            tissue engineering with its ability to create cell-integrated   the mixing of multiple solutions before extrusion offers the
            structures with complex geometries, which were previously   potential for creating structures with various properties.
            unattainable with traditional manufacturing methods.   Multi-material bioinks consisting of solutions such as
            Nevertheless, 3D bioprinting technology is still confined   proteins, hydrogels, and cells can create a more realistic
            by certain constraints. One significant constraint is   3D-bioprinted structure that could be advantageous for
            related to the 3D printing of structures similar to the   tissue engineering applications.
            complex hierarchical structure of natural tissues . Various
                                                  [9]
            3D printing technologies are used today in 3D bioprinting,   In multiple studies, extrusion-based 3D bioprinting and
            such as extrusion-based and vat polymerization.    customized 3D-printed parts have been combined to create
                                                               tissue scaffolds with desired characteristics. For instance,
              Vat polymerization is one of the 3D printing     Khan et al.  combined vat polymerization and extrusion-
                                                                       [21]
            technologies used in fabricating tissue engineering   based 3D bioprinting to create a complex human-like ear
            scaffolds, relying on a light source, and polymerization   structure. Likewise, Abdelrahman  et al. implemented a
            reaction to cure a photocurable bio-based resin . The   hybrid 3D bioprinting and vat polymerization approach
                                                    [10]
            materials utilized in vat polymerization for 3D bioprinting   for the modeling of Parkinson’s disease using dopaminergic
            are usually photocurable resins and photocrosslinkable   neurons . Furthermore, Scott  et al.  have 3D-printed
                                                                     [22]
                                                                                             [23]
            hydrogels.  Using  photocrosslinkable  hydrogel  in  vat   a nozzle to enable multi-material 3D bioprinting using
            polymerization can enable cell encapsulation and replicate   an extrusion-based system. This allows the nozzle to mix
            the extracellular matrix found in native tissue . Elomaa   multiple solutions and create a multi-material structure.
                                                 [11]
            et al.   developed  a bioactive  photocrosslinkable  resin   Through further research, researchers have looked into
                [12]
            derived from a decellularized small intestine submucosa   the advantages of merging various 3D printing techniques
            for vat polymerization-based 3D bioprinting. The   for utilization in different applications [6,24] . It has been
            developed bioactive resin offers a printable material that   demonstrated that the convergence of 3D printing
            acts as a suitable medium for fabricating a complex 3D   techniques can upgrade 3D bioprinters and exploit material
            tissue model. However, vat polymerization application in   characteristics for enhanced printability and resolution.
            fabricating cell-based scaffolds is limited due to the high
            ultraviolet (UV) exposure intensity and the cytotoxicity   Herein, we propose a design and fabrication process
            effect of polymerization reaction . Consequently, this   for disposable nozzle connectors (DNC) to accelerate the
                                       [13]
            technique is limited to fabricating acellular scaffolds that   nozzle-making process for low-viscosity bioinks. It was
            can only be seeded with cells post-printing. Therefore,   curated to allow instantaneous mixing of three solutions for
            other 3D printing technologies can provide the necessary   the formulation of a continuous bioink thread embedded
            freedom in fabricating and mimicking 3D tissue models.  with cells. The connectors were designed to easily fit into
                                                               standard Luer lock needle tips, making them versatile and
              Extrusion-based 3D printing is a technique that is
            widely used in fabricating cell-based scaffolds in the 3D   compatible with a wide range of mixing requirements and
                                                               bioink viscosities. Our design parameters were set for the
            bioprinting process [14,15] . More recently, there has been
            an interest to integrate smart and intelligent biomaterials   material characteristics of peptide bioinks, and several
            with 3D printing technology . A  pressure-based or   tests were performed to assess workability and printability.
                                     [16]
            mechanical feeder is used to extrude material through a   With a thorough evaluation, the developed DNC proved
            nozzle .  While  this  layer-by-layer  approach  facilitates   to be cost-effective, reproducible, and highly practical for
                 [17]
            fabrication, it has limitations with low-viscosity materials   standardization.
            when creating complex structures due to resolution   2. Methods
            constraints  and instantaneous gelation  properties  of  soft
            matter bioinks, such as peptide hydrogels. On the other   With  the  assistance of  vat  polymerization  technology,
            hand, high-viscosity biomaterials produce a high shear   several DNCs were designed to suit peptide bioink
            force, resulting in a high degree of cell destruction during   requirements and 3D-printed with varied final diameters
            extrusion. Often, cross-linking methods are used to reduce   and mixing regions. An ideal design was selected based
            the viscosity of biomaterials and improve cell viability .   on ease of flow and effective gelation. The 3D-printed
                                                        [18]
            However, alternative solutions could be developed by   DNCs  were  assembled  with  Luer  lock  needle  tips  to
            maximizing  the  instantaneous  gelation  property  of   create fully functional nozzles with multiple inlets and a


            Volume 2 Issue 1 (2023)                         2                        https://doi.org/10.36922/msam.52
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