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International Journal of Bioprinting                         3D printing of smart constructs for precise medicine



            Table 1. Comparison of performances of commonly used 3D bioprinting techniques.
             Technique   Advantages                              Drawbacks                           References
            Inkjet based  • Low cost                             • Low cell density (<10  cells mL )  [45,154-157]
                                                                                6
                                                                                      -1
                        • High cell viability (75% – 90%)        • Low‑viscosity bioinks (~3 – 12 mPa·s)
                        • Fine printing resolution (~30 μm)      • Risk of nozzle clogging
                        • Rapid printing speed (up to 10,000 droplets per second)
            Microextrusion  • High cell density (~10  cells mL , e.g., cell spheroids)  • Low resolution (~100 μm)  [158-162]
                                             -1
                                       8
                        • High viscosity bioinks (30 mPa·s‑6×10  mPa·s×10  mPa·s)  • Slow printing speed (~10 – 50 μm s )
                                                         7
                                                  7
                                                                                         -1
                        • Medium cell viability (40% – 95%)      • High shear stress
                                                                 • Nozzle clogging
            Light assisted  • Ultrafine printing resolution      • High cost                        [159,163,164]
                        • High cell viability (>95%)             • Post‑printing cell damage
                        • High cell density (10  cells mL )      • Difficulty in assembling multiple types of bioinks
                                      8
                                            -1
                        • Low‑viscosity cell suspensions (1 – 300 mPa·s),
                        • Free from nozzle clogging
                                                               3.2. pH-responsive biomaterials
                                                               The development of pH-sensitive biomaterial inks
                                                               to improve the efficiency of drug release for tumor
                                                               therapy is underway [72,73] . Polymers that are used
                                                               to study pH responsiveness include polyacrylate,
                                                               poly(N-isopropylacrylamide), n-vinylcaprolactam, sodium
                                                               alginate, and carrageenan . Bivalent copper can be used
                                                                                   [74]
                                                               in combination with alginate to form biomaterial ink.
                                                               Notably, it has proven in this study that the encapsulation
                                                               system is able to retain its structural integrity at pH = 1.2.
                                                               The contents were then released slowly only at a pH > 5,
            Figure 5. Stimulation-responsive biomaterials in tissue engineering.
                                                               suggesting slow release of the contents in the intestinal
            formulated with polyvinyl alcohol (PVA), which is capable   tract [75,76] . Furthermore, novel biomaterial inks have been
            of  interpenetrating  with  chemically  cross-linked  PEG   developed using a gelation mechanism that crosslinks
            during crystallization. After three cycles of freezing and   polyvinylpyrrolidone  polymer  and  crotonic  acid  under
                                                                                [76]
            thawing, the hydrogel composed of 70% PVA and 30% PEG   gamma (γ) radiation . The drug release rate from the
            exhibited a stable helical morphology. The results of these   resulting gel was much lower in an acidic medium than
            studies showed that the degree of thermoresponsiveness   in a  neutral medium.  Some biomaterial  inks  must also
            was affected by the crystallinity of the polymers. Xu et al.    include the stability of their pores to avoid swelling. Silica
                                                        [71]
            merged dynamic ionic and covalent bonds to formulate a   nanocomposites on top of poly(N-isopropylacrylamide)
                                                                                            [77]
            novel thermally responsive polybutadiene (PB) rubber.   have been employed for this purpose . The pH-responsive
            More specifically, the ionic bonds were formed through the   biomaterial inks depend on the ionic side chains, that is, they
            combination between PB-COOH and PB-NH . Afterward,   depend on the protonation of electrostatic repulsion with
                                                2
                                                                                       [78]
            they were cross-linked with different concentrations of   the surrounding environment . pH-responsive cellulose
            the trithiol cross-linker. The SPB-6% hydrogel exhibited   biomaterial inks have also been used in wound dressings
            a permanent spiral-like structure when the SPB film was   for better skin tissue engineering. These are biomaterial
            photocrosslinked after rolling on a rod. As the spiral   inks that can be degraded on acidic skin and have the
                                                                                                    [79]
            biomaterial ink was heated to 60°C, the structure was   ability to self-heal. For example, Akhlaghi et al.  revealed
            changed into a temporary flat shape, which reverted to   that the functionalized cellulose nanocrystals (CNCs) with
            spiral  shape  on  cooling.  This  transformation  may  have   amine (CNC-NH ) moieties could lead to pH-responsive
                                                                             2
            been caused by the thermoreversibility of the ionic   characteristics. The biomaterial ink was degraded at a low
            bonds. Different types of thermoresponsive materials are   pH. This ink can be added into a poly(vinyl acetate) to
            widely utilized in various tissue engineering applications.   obtain pH-responsive composite nanofilms. In addition,
            Therefore, they have great potential in smart 3D bioprinting,   pH-responsive characteristics can be used to improve
            in which the shape of biomaterial ink can be transformed   micropores within a biomaterial ink [80,81] . For example,
            by altering the temperature within ideal ranges.   Bao et al.  manufactured micropore-forming viscoelastic
                                                                      [80]

            Volume 9 Issue 1 (2023)                        238                      https://doi.org/10.18063/ijb.v9i1.638
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