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International Journal of Bioprinting                                     3D bioprinting for vascular system




            4.1. Bio-inks with good performance                epithelial cells and stimulate the formation of vascular
            Making a printable pro-angiogenic bio-ink includes   buds in the wound surface . Bacterial cellulose is an
                                                                                      [47]
            mixing  multiple  hydrogels  and  chemically  modifying   organic compound biosynthesized by  Gluconacetobacter
            a single hydrogel. Substances that improve rheology or   xylinus. After dehydration, the bacterial cellulose matrix
            elasticity are added to compound bio-inks to optimize the   can generate a microchannel structure for cell adhesion
            mechanical properties of naturally derived hydrogels. Wu    and proliferation in the vascular scaffold and promote the
            et al. synthesized a shrinkage glycyrrhizin-methacrylate silk   construction of a smooth muscle layer in the vascular wall
            (SilkMA) with excellent mechanical properties and mixed   (Figure 3B) . De-cellularization of tissues is a promising
                                                                        [48]
            it with GelMA and sodium alginate . They found that the   technique that allows the removal of cellular components
                                        [42]
            higher concentrations of GelMA (7.5%) and SilkMA (20%)   while preserving ECM structure and  composition. By
            were better suited for cell adhesion and proliferation, and   mixing pig ovary dECM solution with seaweed gelatin
            by using this method, they rapidly generated an inch-long   mixture solution, the printed ovarian 3D scaffold
                                                [42]
            blood vessel construct in as little as 3 days . Xanthan   showed more positive signals for new angiogenesis, cell
                                                                                                 [49]
            gum is a microbial extracellular polysaccharide produced   proliferation, and survival (Figure 3C) . ECM  not
            by fermentation engineering, which has good rheology   handled thoroughly poses a threat to the body’s immune
            and  biocompatibility.  Muthusamy  et al.  utilized  xanthan   response or pathogen transfer. Oliveira et al. solved this
            gum as a collagen thickener and found that collagen bio-  problem using a cell assembly extracellular matrix (CAM)
            ink with 10 pc xanthan gum added has the best printing   synthesized from normal skin fibroblasts in vitro . The
                                                                                                       [50]
            adaptability, shape fidelity, and good capillary network   thick structure printed by CAM can support the survival
            generation . Laponite is a montmorillonite nanoclay   and maturation of capillary networks and successfully
                    [43]
            suspension that self-assembles to form a reversible shear-  connect with the host circulatory system to establish
            dilute gel. Laponite and alginate nanocomposite showed   active perfusion .
                                                                            [50]
            improved rheological properties,  printing compatibility,   Sacrificial bioprinting is a classic indirect bioprinting
            and higher  recovery  rate  after  shear  under  higher  clay   method. Sacrificial bioprinting of vascularized tissue
            concentration, and the constructed bone tissue scaffold   removes soluble bio-inks, usually through temperature
            showed in vitro angiogenesis ability . Poly (itconic acid-  change or enzymatic ablation, leaving behind a perfusable
                                        [44]
            co-citrate-co-octanediol) and poly (octanediol-co-maleic   channel. Indirect printing is usually bioprinting based on
            anhydride-co-octanediol) are synthetic elastic polymers   extrusions with low resolution and minimum characteristic
            that can be mixed with hydrogels to improve their stability   sizes  larger  than  100  μm,  making  them  less  suitable  for
            and elasticity. Cell traction or body movement prevents the   fabricating capillary structures. How to improve the
            resulting blood vessels from irreversible deforming .  resolution of sacrificial bioprinting is a new research
                                                    [45]
               Endothelial  cells  can  regulate  vascular  inflammation   direction. Li  et  al. combined a heat-sensitive polymer
            and thrombosis, and rapid endothelialization of early   (n-isopropyl acrylamide) with biocompatible GelMA to
                                                                                          [51]
            vascular  grafts  can  effectively  prevent  the  blockage  of   form a heat-responsive hydrogel . In cell culture, the
            small-diameter vessels. The biological properties of   thermo-responsive hydrogel underwent significant volume
            bio-inks are essential for the rapid endothelialization of   shrinkage, which effectively triggered the production
            vascular grafts. To improve the ability of hydrogel scaffolds   of smaller microscale vasculatures, with a minimum
                                                                              [51]
            to promote the formation of microvascular networks,   diameter of 50 µm . Thomas et al. have proposed a two-
            substances that can induce the adhesion and proliferation   component biomaterial system using a photo-crosslinked
                                                                                                           [52]
            of endothelial cells can be added to the composite bio-ink.   methacrylate hyaluronic acid (HAMA) and GelMA .
            Natural alginate is biologically inert but can be modified   With highly-resolution enzyme-digested photo inks based
            with cell adhesion peptides to customize its biological   on hyaluronic acid and the complementary enzyme, they
            activity with excellent performance, precision, and control.   printed vascular structures using stereolithography 3D
                                                                        [52]
            To promote vascular morphogenesis, Barrs et al. modified   bioprinting .
            alginate scaffolds to promote vascular morphogenesis
            using RGD (an integrin-binding peptide for cell adhesion)   4.2. High-resolution printing technology
            and vascular endothelial growth factor (VEGF) mimic   Currently,  most  microvascular  networks  are  constructed
            peptides (Figure  3A) .  Paeonia  lactiflora extract is a   by an uncontrolled spontaneous induction because
                              [46]
            compound derived from the herb peony that regulates   previous printing techniques have not been able to
            the inflammatory microenvironment in skin wounds.   accurately print microvessels with an internal diameter of
            Combining 3% paeoniflorin with a 3D mesh structure   fewer than 500 microns. The vascular network formed by
            of the scaffold can promote the secretion of collagen by   self-assembly, which is less efficient in material exchange

            Volume 9 Issue 6 (2023)                        263                          https://doi.org/10.36922/ijb.0012
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