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International Journal of Bioprinting                                  3D bioprinting of artificial blood vessel


            the  primary technique of vat polymerization  printing,   5. Conclusion and future perspectives
            enables relatively fast production of volumetric structures
            with  precise  internal  and  external  architectures.   Bioprinting has an important place in the field of tissue
            Stereolithography  was  developed  in  the  1980s  and  was   repair  due  to its  ability to  spatially deposit biological
            one of the first commercial additive manufacturing   materials in a layer-by-layer manner. Bioinks are a
            processes [191] . The 3D models (inlets, outlets, and a box-  core aspect of bioprinting because they undertake
            like container) for stereolithography were designed in   the  responsibilities  in  organizational  formation  and
            Blender CAD software [192] . Han et al. developed a vascular   supporting  cell viability. Therefore, bioink  consists of
            network by adhering to a set of comprehensive design rules   special elements, such as ECM component and nutrient
            to design a blood vessel network on a skin patch [193] .  substance. The ideal bioink should have better printability,
                                                               high degree of biocompatibility and biodegradability, as
              Some  of  the  advantages  of  vat polymerization are  the   well as can be completely cured by cell-friendly treatment.
            improved the manufacturing rate and the ability to generate   Designing  the  ideal  bioinks  that  have  high  mechanical
            objects with smooth surface (overall high resolution), which   strength and can support cell migration or proliferation is
            overcome  major  disadvantages  of  contemporary  additive   highly challenging. Until now, various kinds of hydrogel
            manufacturing. The limitation of this method is the diameter   have been introduced in this area, such as the HA, collagen,
            of the vessel that needs to be narrowed down to a range of   alginate, fibrous protein, and dECM. However, it is hard
            100 – 400 μm [192] . It is important to note that comprehensive   for these materials to simulate the natural ECM due to
            studies on using vat polymerization to rebuild blood vessel   the complex topologies and components. The dECM is
            are scarce. Besides, the materials with low stiffness are suitable   a promising bioink material with bionic properties for
            to rebuild the soft tissue that needs better cell viability, while   establishing  artificial  blood  vessel;  however,  enhancing
            stronger materials are used in stereolithography to achieve   support capability is a challenge. Common methods for
            high-resolution construction, which hinders the application   addressing  this  include  increasing  the  concentration
            of this method in blood vessel bioprinting.        of the dECM, adding biological molecules such as HA,
                                                               collagen or  alginate, or  changing the  cross-linking
            4.4. Freeform reversible embedding of suspended    method.
            hydrogel (FRESH)
                                                                 The ultimate objective of 3D bioprinting is to print the
            To bioprint the complex blood vessel structures, FRESH is   injured or damaged organ  in situ. At recent stage, only
            a method using a thermoreversible support bath to enable   bioprinting of the shallow tissue (such as skin, cornea, or
            deposition of hydrogels [194] . The technique revolves around   cartilage) is almost achievable. In regard to the artificial
            printing a structure in the support bath to maintain
            the expected structure and printing fidelity [195] . The   blood vessel, the current technology is only capable of
            thermoreversible support bath is made of gelatin particles,   pre-fabrication and further  in vitro maturation before
            which is similar to Bingham plastics, and they behave as   implantation. In the in situ printing of blood vessel, a faster
            rigid bodies at low shear stresses but as viscous fluids at   cross-linking method is needed in the FSCR system, which
            higher shear stresses [196] . These properties ensure that the   needs to be combined with the scanning system and 3D
            bath is at a low mechanical resistance when the needle   rebuild software. Besides, more attention should be paid
                                                               to the sterilization and safety of the  in situ bioprinting
            moves across, while the hydrogel is kept in place after   systems.
            being extruded from the nozzle at 22°C. After completing
            the structure, the temperature is increased to 37°C and the   The challenges that hinder the development of artificial
            gelatin will melt in a nondestructive manner. This method   blood  vessel  are  the  regulatory  processes  and  funding
            requires that  the  bioink  must  gel  quickly  to  a fine  wire   approval. The Current Good Tissue Practice for human
            without spreading in the support bath. Hinton et al. used   cell, tissue, and cellular and tissue-based product by the
            the alginate-CaCl 0.16%) system to print in the FRESH   FDA requires that the bioinks must be manufactured
                          2 (
            and obtained the 199 ± 41 μm fine wire, and fabricated the   in  adherence  to  the  stipulated  guideline.  For  example,
            right coronary artery vascular tree with a wall thickness   the preparation of bioink and cells should be more than
            of <1 mm, as shown in Figure 11 [196] . Lee et al. also used   1 – 3 months, and in vitro cell culture may lead to unexpected
            the FRESH to design the human heart components of   cell differentiation, increase the risk of infection, and raise
            all sizes, from the capillaries to the whole organs [197] .   the production cost. Besides, the FDA guidelines clearly
            Following the regulation of the collagen pH, the resolution   require that no more than 1 living microbe can be detected
            of fabricated items could reach up to 10 microns with cells,   in every million sterilized final products of the blood
            and the microvessels fabricated using FRESH had optimal   vessel prosthesis. Therefore, for bioinks made by natural
            mechanical strength and cell viability [197] .     materials, sterilization technique is the final difficult aspect


            Volume 9 Issue 4 (2023)                        425                         https://doi.org/10.18063/ijb.740
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