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International Journal of Bioprinting                                        Progress in bioprinting of bone




























            Figure 2. Bioprinting technologies for bone tissue. (A) Extrusion-based bioprinting with traditional pneumatic/piston extrusion (A1), coaxial nozzle for
            the printing of core-shell filaments (A2), dual-nozzle setup for bioprinting of multiple bioinks (A3), and post-printing polymerization for photocurable
            bioink, (B) droplet-based bioprinting, (C) laser-based bioprinting, and (D) aspiration-assisted bioprinting.

            main components of bone, including HAp and tricalcium   vascular  network  with  anatomic  similarity.  In  one  case,
            phosphate (TCP) [33-35] , as well as polycaprolactone (PCL),   a geometry consisting of two phases was envisioned,
            polylactic acid (PLA), and polyether ether ketone, which   with HAp forming part of the shape (bone tissue) and
            are known for their great mechanical properties .   alginate and gelatin filling the tubular structure (vascular
                                                        [36]
                                                                       [51]
                                                                                                 [52]
            Furthermore, studies have been conducted with 45S5   structure) . Moreover, Byambaa  et al.  designed a
            Bioglass, polyP, and biosilica, which enhance the ability   pyramidal construct that included a perfusable vascular
            of cells to synthesize mineral deposits and induce   lumen and was functionalized with gradient concentrations
            the expression of alkaline phosphatase (ALP), bone   of  vascular  endothelial growth  factor  (VEGF).  Media
            morphogenetic protein 2 (BMP-2), and COL-I [37,38] .  perfusion for 5 days was performed to produce a hollow
                                                               perusable main vessel. For example, Cui et al.  fabricated
                                                                                                   [53]
            2.3. Vascularized bone structure                   a biphasic structure using a dual bioprinting procedure
            Considering that bone is a complex tissue with a hierarchically   that combined fused deposition modeling (FDM) and
            organized structure, biomimetic design becomes an essential   stereolithography (SLA). The honeycomb-pored units in
            consideration. Cells within the bone are encapsulated by the   the hard portion of the scaffold mimicked the osteon or
            mineral matrix, which is surrounded by blood vessels [39-42] . It   Haversian system of bone, while the channels filled with
            is widely recognized that interconnected pores are necessary   GelMA hydrogel resembled the vascular system. Cell
            for the growth of blood vessels. According to the general   growth and expansion in the hydrogel were expected to
            viewpoint of tissue engineering, a pore size of 5 microns is   render the formation of capillaries.
            optimal for neovascularization, 5 – 15 microns for fibroblast   2.4. Cell source
            ingrowth, 40 – 100 microns for osteoid ingrowth, and 100
            – 400 microns for bone regeneration [43,44] . Other than the   Bone bioprinting has continued to use similar cell types that
            use of porous structures, a number of strategies have been   are popular in bone tissue engineering. A mouse osteoblast
            developed to promote angiogenesis, including the use of   precursor cell line (MC3T3) has been proven to be highly
                                                    [47]
            angiogenic growth factors [45,46] , dynamic culture , and   feasible and physiologically relevant for bone bioprinting.
            coculture of endothelial cells (ECs) with mesenchymal stem   Nevertheless, it is important to exercise caution when
                                                               extrapolating these results to primary cells. In research
            cells (MSCs) [48-50] .
                                                               pertaining to the bone, human osteosarcoma cell line
              A functional blood vessel system at the network level   (SaOS-2) that is derived from the primary osteosarcomas
            within the implant is required for the effective restoration   is commonly used as osteoblast-like cells . The SaOS-2
                                                                                                 [54]
            of  bone.  It  is  expected  that  the  endothelium  and  vessel   cell line has several advantages, including the ability to
            wall are organized in a networked fashion. In this context,   propagate quickly and to differentiate in a manner similar
            bioprinting is possible to remodel a hierarchically branched   to that of osteoblasts .
                                                                               [55]

            Volume 9 Issue 1 (2023)                         80                      https://doi.org/10.18063/ijb.v9i1.628
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