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     International Journal of Bioprinting                             Bio-inks for 3D printing cell microenvironment
            Table 1. Stiffness values of living tissues at different scales
             Tissue          Modulus      Modulus value     Dimension      Test mode                     Refs.
             Bone            E            1.28–1.97 GPa     Nanoscale      AFM                           [36]
             Bone            E            10.4–20.7 GPa     Macroscale     USE, Micro-tensile            [29]
             Cardiac muscle  E            8 kPa             Macroscale     MRE, Tension                  [84]
             Cardiac muscle  G            5–50 kPa          Macroscale     USE, MRE                      [85]
             Lung            G            0.84–1.5 kPa      Macroscale     MRE                           [86,87]
             Lung            E            1.96 kPa          Nanoscale      AFM                           [88]
             Liver           E            1.5–6.5 kPa       Macroscale     USE, Cyclic compression-relaxation  [89–91]
             Liver           G            2 kPa             Macroscale     MRE                           [92,93]
             Liver           E            162–248 kPa       Macroscale     Probing (Entire organ)        [94]
             Pancreas        E            2.8 kPa           Macroscale     USE                           [95]
             Pancreas        G            1.11 kPa          Macroscale     MRE                           [96]
             Kidney          E            1–2 kPa           Nanoscale      Nanoindentation               [74]
             Kidney          E            35.3–68.9 kPa     Macroscale     Probing (Entire organ)        [94]
            Abbreviations: AFM, atomic force microscopy; E, elasticity modulus; G, shear modulus; MRE, magnetic resonance elastography; USE, ultrasonic
              elastography.
            properties of the material itself, which is independent   bone’s porous 3D structure enhances the overall system’s
            of shape and structure. However, given the inseparable   stiffness .
                                                                     [33]
            complexity of biomaterials (especially polymeric materials
            and anisotropic biological tissues), the “stiffness” for   It is worth noting that although most studies provide
            biomaterials in research is often characterized using   specific values for tissue stiffness, there is no gold standard
            modulus (e.g., elastic modulus). In many studies, although   test for measuring stiffness in biological tissues. Stiffness
            a piece of tissue may contain both, dense fibers and   values in tension (elastic modulus), compression (elastic
            loose matrix at the molecular (microscale) level, it is still   modulus), and shear (shear modulus) are likely to differ for
            measured  as a whole, without considering the  uneven   bulk structures, and tests for surface stiffness (indentation
            distribution of matter at a smaller scale.         test) may provide different stiffness values. For cellular
                                                               stiffness, measurements by atomic force microscopy
               Living tissues have a wide range of stiffness, especially   (AFM)  and optical tweezers  are commonly used. This
                                                                    [34]
                                                                                       [35]
            in  higher  animals with more  complicated structures,   leads to significant differences between the macroscale
            such as the intuitive difference in stiffness between a   and microscale stiffness  of the same material. When
            “hard” bone and a “soft” brain . Comparing only in   bone tissue is measured at the microscopic scale, it may
                                      [28]
            terms of elastic modulus, the elastic modulus of bone is   only show a stiffness of 1.97 GPa , which differs from
                                                                                           [36]
            as high as 20 GPa , while that of mucus is only 11 Pa .   the macroscopic result. Living tissue  in vivo is usually
                          [29]
                                                        [30]
            The specific functions of distinct organs determine the   measured using elastography (Table 1). Table 1 shows the
            variances in stiffness of living tissues (e.g., weighed bone   stiffness values measured by different methods for certain
            has the highest stiffness of all tissues), and the cells within   living tissues in the human body.
            the matrix have specialized interactions with the stiffness
            microenvironment. The stiffness of abnormal tissues also   Different organs or tissues have specific structures,
            has its own specificity. For instance, there is significant   owing to the uneven distribution of internal substances.
            difference  in  tumor  stiffness  among liver  malignancies,   For example, more fibers confer elasticity to blood vessel
            with cholangiocellular carcinoma (75 kPa) being stiffer   walls. The renal cortex has more blood vessels than the
            than hepatocellular carcinoma (55 kPa) and metastatic   renal medulla. This macrostructure has a decisive influence
            tumors (66.5 kPa) . This stiffness difference may provide   on the overall mechanical property. According to Table 1,
                          [31]
            the basis for clinical diagnosis. It is also worth noting that   intact livers and kidneys have high compressive moduli,
            cell stiffness differs from tissue stiffness. Although bone   allowing them to withstand certain shocks without damage.
            has a stiffness of 20 GPa, the stiffness of osteoblasts, which   However, in micromechanical tests, in which organs are
              are cells that synthesize bone, is only 2.6 kPa (unspread   cut into small samples, they show mechanical properties
            spherical) or 6.5 kPa (spread) . Hard bone is the result   on the  order of magnitude of lungs.  By eliminating the
                                    [32]
            of the accumulation and mineralization of ECM and the   effects of part of the macrostructure, seemingly dissimilar
            Volume 9 Issue 1 (2023)                        147                     https://doi.org/10.18063/ijb.v9i1.632





