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International Journal of Bioprinting                                         Hydrogels for 3D bioprinting



            Regenerative medicine employs methods to repair the   Applying suitable bioinks is the fundamental of 3D
            functions of cells, tissues, or organs, which are diseased   bioprinting. The general definition of bioinks is a formula
            or damaged, through substitution or regeneration [2,3] .   containing biomaterials and bioactive components that can
            Tissue engineering and regenerative medicine are two   be processed by automated manufacturing technology .
                                                                                                           [14]
            highly interrelated and multi-disciplinary research fields.   The types of bioinks include hydrogels, cell aggregates,
            However, in practice, the definitions of these two concepts   acellular matrix, etc. [15,16] . The ideal bioinks containing cells
            are  not  identical.  Regenerative  medicine  is  a  broader   should be smoothly squeezed out of the printing needle
            definition that not only includes tissue engineering, but   without damaging the cells due to shear stress [14,17,18] .
            also includes self-healing of the body’s tissue systems.   The hydrogels are high-molecular-weight polymer with
            Tissue  engineering and  regenerative  medicine are  now   a 3D-crosslinked network structure and water content
            widely conflated, mainly because the ultimate goal of   equivalent to soft  tissue, which is a commonly type  of
            tissue engineering is to replace or enhance the self-healing   bioinks applied in 3D bioprinting owing to its excellent
            of tissues. Many researchers have used biological and   characteristics of simulating extracellular matrix (ECM)
            engineering approaches to achieve the goal of promoting   and printability. Hence, the general conventional definition
            the repair and regeneration of tissues or organs, or even   of  bioinks  refers  to  a  cell-loaded  hydrogel  formulation
            giving them a normal structure or function. Magalhaes   that can be processed by automated biomanufacturing
            et al.  used autologous primary uterine cells attached   technologies . For a proper 3D bioprinting process,
                                                                         [14]
                [4]
            to a semi-circular poly-dl-lactide-coglycolide (PLGA)   it is necessary to have both hydrogel bioinks capable of
            and polyglycolic acid (PGA) biodegradable scaffold to   producing cell-loaded bioinks and a multi-scale spatial
            repair and reconstruct uterine defects in larger animal   resolution that can mimic the native ECM . The
                                                                                                      [19]
            models (i.e., rabbits), thus enabling the complete process   ideal hydrogel materials should have a series of good
            of pregnancy to term births. However, repairing and   physical, chemical, and biological characteristics, such
            regenerating larger animal models or human uterine   as printability, biocompatibility, degradability, mechanical
            defects by the same method failed [5, 6] . Although  in   properties, stability, non-toxic, and non-immunogenic
            vitro biomimetic tissues and organs can be made using   properties, and should be able to promote cell adhesion
            traditional  methods  that  include  electrospinning [7,8] ,   proliferation and differentiation [15,19,20] . First of all, from the
            rapid prototyping , and freeze-drying , the designed   aspect of printability, hydrogel bioinks for printing should
                          [9]
                                            [10]
            biomimetic tissues or/and scaffolds are difficult to form   possess several characteristics: (i) Shear-thinning. It is
            the  three-dimensional  (3D)  structures  compared  with   expected that the viscosity of the hydrogel is lower at high
            natural tissues or/and organs. Cells cannot be uniformly   shear rates. Because high shear thinning is beneficial to
            attached to traditional scaffolds and cannot proliferate and   improve cell viability, it can also maintain the shape fidelity
            differentiate. Therefore, the scaffold without physiological   of the scaffold after printing. (ii) Yield stress; to prevent
            activity will cause cell death and further cause tissue or/  the spread of bioinks on the surface. (iii) Self-healing. The
            and organ necrosis if cells are directly seeded .  viscosity of the hydrogel will change during the extrusion
                                                [11]
                                                               printing process, and the original viscosity is expected to
               3D printing is an emerging technology that has been   restore after printing. (v) Crosslinking ability, that is, the
            widely applied in the field of tissue engineering. Compared   process of gelation has stability in physical, chemical, or
            with traditional manufacturing technologies, it has made   biological media crosslinking agent. (v) Degradability.
            great progress, but there are still problems, such as low cell   The hydrogel and the by-products produced should be
            seeding efficiency, uneven distribution, and low spatial   biocompatible when degraded, with less toxicity or even
            resolution. Therefore, 3D bioprinting which combines   non-toxicity [21-25] . Therefore, in this review, we discuss and
            cells and biological materials has become a more attractive   summarize the researches of 3D bioprinting using hydrogel
            technology . 3D bioprinting can construct complex   as bioinks in recent years. According to the commonly
                     [12]
            and cell-loaded 3D structures, which are helpful for the   used classification methods of hydrogels, the preparation
            application of scaffold-based or scaffold-free tissue and   methods  such  as mixing, chemical  modification, and
            organ structures, microorganisms, and single-chip organ   nanodoping are analyzed from the perspective of different
            model systems. Generating functional human organs   printing technologies. At the same time, we discuss
            and tissues like the heart, liver, skin, and cartilage on the   the advantages and disadvantages of several common
            upcoming large-scale human body will play an essential   hydrogel bioinks available today, and present some ways
            role. With the increasing development, 3D bioprinting   to avoid the shortcomings so that these hydrogels can be
            technology is leading a global revolution in the medical   better matched with 3D bioprinting for tissue engineering
            field, and enormous changes will take place in the treatment   applications. We expect to discover the optimization and
            of diseases in the near future [2,13] .            improvement of  3D  bioprinting  technologies  to  realize

            Volume 9 Issue 5 (2023)                        209                         https://doi.org/10.18063/ijb.759
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