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International Journal of Bioprinting                                         Hydrogels for 3D bioprinting



            is difficult to use them alone as bioprinting inks, so many   chitosan affects the stability of the scaffolds, they first tested
            researchers introduced exogenous crosslinking methods   the  high-molecular-weight  and  low-molecular-weight
            or mixed natural polymer-based hydrogels with other   chitosan materials. Then, the ratio of the materials was
            polymers or printed them with other structural support   optimized. Under low ratios (1:5 and 1:10) and high ratios
            materials, and the hydrogels can be tissue-specific adjusted   (1:10 and 1:15), the results showed that high-molecular-
            to the specific repair site and repair modality. For example,   weight chitosan has lower mechanical properties and
            genipin crosslinking of gelatin will lead to reduced swelling   smaller  cell  adhesion. However, low-molecular-weight
            and increased hardness of gelatin due to the powerful   chitosan exhibits a good outcome. In the end, they chose
            crosslinking effect of genipin. Therefore, it is more suitable   low-molecular-weight chitosan and PEGDA to study the
            for the repair of hard areas such as bone tissue. In contrast,   optimal ratio, which is 1:7.5.
            crosslinking of gelatin with mTG provides gelatin with   The bioink of this ratio is suitable for the printing
            uniform pore space and higher swelling properties, making   of complex shapes. They created a human ear-shaped
            it more suitable for repair of soft tissue sites and endowing   scaffold that showed interconnected porous structures
            it with the ability to load or encapsulate other substances   after freeze-drying. Human bone marrow mesenchymal
            such as drugs  or cytokines. These approaches provide   stem cells (hBMSCs) can adhere to the scaffold and
            useful assistance for people to use natural polymer-based   proliferate. Jia et al. [78]  designed a hybrid bioink composed
            hydrogels as bioinks for 3D bioprinting in the future.  of 4-arm poly (ethylene glycol)-tetraacrylate (PEGTA)
            3.2. Synthetic polymer-based hydrogel              and other hydrogels combined with a multi-layer coaxial
            The most common synthetic hydrogels are alcohols,   extrusion system. Through ionic bonding and covalent
            acrylates, and their derivatives, such as PEG and PEGDA,   photocrosslinking, a highly organized perfusion vascular
            polyacrylamide (PAAM), and polyurethane (PU) [39,53,76] .   structure  is  formed.  The  addition  of  PEGTA  enhances
            Besides, Pluronic is also a common sacrificial material.   the mechanical properties of the scaffold. Compared
            We can process and modify natural hydrogels according   with linear PEG molecules, PEGTA scaffold allows better
            to requirements.                                   cell growth.
                                                               3.2.2. Pluronic
            3.2.1. Polyethylene glycol                         Pluronic, which is the trade name of poloxamer, is a synthetic
            PEG has good biocompatibility, non-immunogenicity, and   block polymer composed of a hydrophobic polypropylene
            non-toxicity, but due to a lack of cell adhesion sites on the   oxide (PPO) block and two hydrophilic polyethylene oxide
            surface, it cannot provide a suitable growth environment   (PEO) blocks. The Pluronic gel is a temperature-sensitive
            for cells. Therefore, it is often modified by blending,   polymer with reversible gel properties; the gelation
            grafting, and interpenetrating with natural polymer   temperature of it depends on its type and concentration.
            hydrogels to optimize the performance of hydrogels [39,77] .   Unlike gelatin and SA hydrogel, Pluronic is liquid at low
            PEG  and  SA can  form  an  interpenetrating  network to   temperatures  (usually  4°C),  forms  a  physical  gel  at  high
            stably keep the 3D structure of the hydrogels in the form   temperature (37°C), and can be dissolved in deionized
            of covalent crosslinking. Different molecular weights of   water. Therefore, after printing scaffolds, lowering the
            PEG and different crosslinking agents have a tremendous   temperature can remove Pluronic smoothly [79-81] .
            impact on the elasticity of the hydrogel. The application of
            Ca -containing crosslinking agents in PEG-SA hydrogels   Pluronic materials show better results in cartilage
              2+
            can significantly increase its fracture energy. Conversely,   tissue engineering. The high concentration of Pluronic can
            with the molecular weight of PEG increasing, the length   meet the rheological and gelling conditions required for
            of the polymer chains also increases, resulting in higher   extrusion printing. For example, Müller et al. [80]  proposed
            tensile properties and higher fracture energy of the   a nanostructured method that can meet the performance
            hydrogel . PEG is usually used as a light-curing material   requirements of Pluronic F127 gels during the entire
                   [53]
            after modification. PEG derivatives are mainly PEG   bioprinting process.  The pure  Pluronic  F127  hydrogel
            acrylates, which include PEGDA, PEG dimethacrylate   cannot culture cells for a long time. But after acrylate
            (PEGDMA), and multi-arm PEG acrylates [39,78] . As a   modification, a high concentration of Pluronic F127 is used
            bioink for 3D bioprinting, a blended solution of chitosan   in the printing process, and then it is eluted for chondrocyte
            and PEG acrylic hydrogel is a potential candidate material.   culture. The results showed that cell viability increased
            Morris et al.  used chitosan and PEGDA as bioinks to   from 62% to 86%. Besides, to improve the mechanical
                      [39]
            print scaffolds through stereolithography technology, and   properties of Pluronic F127 hydrogel, a photocrosslinked
            its mechanical strength met the requirements of cartilage   hyaluronic acid methacrylate (HAMA) is mixed to form a
            tissue engineering. Because the molecular weight of   stable network structure. Pluronic F127 is usually used as


            Volume 9 Issue 5 (2023)                        214                         https://doi.org/10.18063/ijb.759
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