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International Journal of Bioprinting                                3D bioprinted vascularized tissue models



            Table 1. Major 3D bioprinting strategies for developing vascular structures
             Bioprinting   Descriptions                             Major benefit in vascularized tissue construction
             strategies
             Coordinated   Spatial arrangement of cell-laden or cell-compatible inks   Coordinated (spatially defined) patterning of desired vascular
             patterning    at desired locations to produce 3D cellular construct with   cell sources and pro-angiogenic factors with high design
                           inter-connected pre-vascular networks    flexibility of manipulating internal structures and porosity
                                                                    throughout the construct
             Sacrificial printing  Deposition of a fugitive ink in any desired geometry, followed   Introduction of physical architectures, such as open and
                           by casting and removal of sacrificial material, enabling manual  inter-connected pores or perfusable micro-channels, within
                           cell seeding to create endothelialized channels  3D hydrogel-based constructs with high freedom on designing
                                                                    channel geometries and a wide size range
             Embedding     Extrusion of designated ink materials into the liquid sus-  Beneficial for improving printability of soft bioink and for
             printing      pension bath to hold the printed filaments and their desired   increasing structural integrity with high design flexibility and
                           geometry while printing                  resolution
             Coaxial printing  Through a core/shell printing configuration, simultaneous   Direct printing of freestanding tubular structure with high
                           extrusion of different materials to create hollow tubular struc-  dimensional flexibility (e.g., diameter, wall thickness, and
                           tures in a single process                length) in a uniform size

            2. 3D bioprinting strategies to build              vascularized tissue constructs. Further, through a multi-
            vascular structures                                material printing process, spatial patterning of vascular
                                                               precursors at desired locations using cell-laden or cell-
            Numerous 3D bioprinting techniques, such as inkjet-based,   compatible materials as (bio)inks can produce a 3D cellular
            laser-assisted, and extrusion-based ones, are being used to   construct with inter-connected pre-vascular networks.
            develop multi-scale vascular structures. The fundamental   For example, Jang  et  al.  developed multi-cellular and
                                                                                   [26]
            principles and characteristics of prevailing bioprinting   multi-layered constructs through the 3D spatial patterning
            techniques have already been extensively reviewed   of vessel-forming cell sources and pro-angiogenic
            elsewhere [22-25] . Among these prevailing techniques,   growth factors to achieve a pre-vascularized cardiac
            extrusion-based  bioprinting  is  widely  employed  to   patch, resulting in improved cell–cell interaction and
            fabricate complex hierarchical vascular structures. Thus,   differentiation as well as vascularized tissue regeneration.
            here we focus on the application of extrusion-based   Maiullari et al.  presented a multi-cellular 3D bioprinting
                                                                          [27]
            bioprinting methods. In extrusion-based bioprinting,   approach to fabricate heterogeneous vascularized cardiac
            cells are encapsulated in an exogenous biomaterial ink   tissue by tailoring the spatial organization of the two cell
            (i.e., hydrogel), which acts as the supporting matrix.   types,  which  can facilitate  enriched  vascular  networks.
            According to the programmed G-code, the designated   Bioprinted constructs with pre-patterning of vascular
            3D tissue structure can be created. Once the printing   precursors can possibly use paracrine signals to enhance
            process is completed, the cell-laden construct undergoes   cell–cell communication and differentiation capacity,
            solidification to retain its desired shape. The extrusion-  thereby improving the vascularization of the engineered
            based method is preferred over other bioprinting methods   tissue.
            owing to its ability to utilize a broad library of biomaterials
            with high-viscosity inks at a higher cell density. In this   Employing the coordinated pattering strategy is
            section, we outline the prominent extrusion-based   beneficial for the precise spatial localization of desired
            bioprinting strategies and elaborate on their principles for   cell types and bioactive molecules and provides high
            vascularized tissue fabrication (Table 1).         design flexibility by allowing the manipulation of internal
                                                               structures and porosity throughout the construct.
                                                               However, the integrated processing of multiple materials
            2.1. Coordinated patterning                        poses technical drawbacks, such as cross-compatibility
            Coordinated patterning strategy refers to the subsequent   between  the  materials  and  rapid  solidification  for  stable
            process of extruding at least one cell-containing ink and one   construction, all of which require continuous efforts in
            biomaterial ink by iteratively switching between different   advancing bioprinting techniques and biomaterials.
            printing heads and spatially pattering them on demand.
            Based on the primary mechanisms of vasculogenesis and   2.2. Sacrificial bioprinting
            angiogenesis in the formation of vascular networks ,   As a top-down approach, sacrificial bioprinting deposits a
                                                        [9]
            coordinated (spatially defined) patterning of vascular   fugitive material in any desired geometry and subsequently
            cell sources and pro-angiogenic factors allows to build   casts it onto another hydrogel. “Sacrificial” ink materials


            Volume 9 Issue 5 (2023)                         17                         https://doi.org/10.18063/ijb.748
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