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International Journal of Bioprinting                         Application and prospects of 3D printable microgels



            structures. Simply put, microgels, which are formed from   simulate the in vivo structure of neural tissue. Microgels
            hydrogel–microgel with certain rigidity, are materials that   have the characteristics to solve the above difficulties,
            can smoothly transition from solid state to liquid state, and   so they have great potential in 3D bioprinting of neural
            vice versa. Therefore, under the impact of printing injection   tissue. The regeneration of cartilage tissue is also a focus
            ports, the microgel liquefies and quickly solidifies after   of 3D bioprinting, as cartilage has limited regenerative
            the external force is removed, forming the desired shape.   capabilities and can be broadly categorized into transparent
            This microgel printing method eliminates the influence of   cartilage, fibrous cartilage, and elastic cartilage, which have
            surface tension, gravity, and particle diffusion, enhancing the   structural and physiological differences. Osteoarthritis
            design freedom of the printed structure. Bhattacharjee et al.    and rheumatoid arthritis are the most common diseases
            utilized microgel support baths to print a range of shapes   that  lead  to  damage  in  joint  cartilage,  and  the  number
            with high aspect ratios, demonstrating the precision and   of patients suffering from these conditions is increasing
            versatility of this method [124] . This type of microgel-based   annually [156,157] . Normal joint cartilage is an inhomogeneous
            printing strategy is versatile and can be extended to various   layered tissue, and this layering is crucial for maintaining
            fields in biomedicine. Compaan et al. utilized this strategy   the structure and function of cartilage [158-160] . Thus, the
            to print the fundamental structure of a vascular system,   particle heterogeneity of hydrogels and higher printing
            namely well-connected branching channels formed by fork   precision can ideally replicate this layered structure for 3D
            printing paths [123] . Jeon et al. employed this strategy to print   bioprinting. In summary, the recent progress of hydrogels
            high-resolution complex 3D structures for the purpose   for 3D bioprinting has been impressive, and it can be
            of repairing bone defects or cartilage injuries [153] . Taken   anticipated that this field will continue to grow and evolve
            together, microgel support baths enable precise and high-  in the coming years, providing solutions for reconstructing
            resolution printing, providing a new strategy for printing   intricate and complex organs and replicating specificity of
            complex organ structures such as vascular and neural tissues.  functional tissues.

               One aspect of 3D bioprinting that has rapidly developed   The use of microgels in 3D bioprinting is still in
            in recent years is the research on new bioinks. Microgels, as   the initial stages of exploration, with many different
            bioinks, are able to replicate specific ECMs while maintaining   approaches being tested, evaluated, refined, integrated, or
            high cell viability and activity, and induce organ-specific   abandoned. In this review, we focus on the use of microgels
            cell behavior. As a new type of bioink, microgel not only   in extrusion-based 3D printing, a technology that we
            have the advantages of common hydrogels, but also make   believe offers unique advantages in terms of simplicity,
            up for their deficiencies, making them more suitable for   versatility, and performance. The future trend of extrusion-
            cell survival and ensuring the performance of biological   based 3D printing is to print multi-layered, high-precision,
            functions. In addition to maintaining cell viability, microgel   biologically functional tissue structures, and to achieve
            can enhance mechanical properties by adjusting the   this goal, extrusion-based 3D printing in the form of
            particle size and assembly mode, thus meeting the stability   coagulation and support baths has been proposed in earlier
            requirements of various organ structures. The complexity   studies, and even further coaxial extrusion systems have
            of organ structure is also a difficulty in 3D bioprinting.   been proposed. Despite the limitations related to materials,
            By  using a  microgel support bath, higher  degrees  of   microgels are perfectly adapted to the support bath system.
            freedom can be achieved for precise printing, providing   Therefore, in the future, the extrusion-based 3D printing
            an effective solution for printing precise tissue structures.   approach should probably focus on the support bath system
            Although the research prospects of microgel as a new   of microgels. Second, the development of heterogeneity of
            type of biological ink are very attractive, many challenges   microgels is the focus of future development. Based on the
            still need to be overcome in order to achieve clinical   complexity of the structure and function of cells, tissues
            translation. To achieve ideal 3D bioprinting, it is necessary   and organs, the interconnection of multiple cells, growth
            to recreate the complex structure and biological function   factors and cellular microenvironment should be the focus
            of tissues and organs. For example, vascular networks,   of 3D bioprinting in future. The availability of a diverse
            nervous tissue, and cartilage tissue all have complex   array of microgels enables 3D bioprinting involving
            structures and functions [125,154,155] . At present, vascularized   multiple cells or growth factors from the bottom up. In
            tissues or independent microvascular network structures   addition,  microgels with  micron-sized pores are  more
            can be printed through the use of microgel support baths.   suitable for simulating cellular microenvironment.
            There are two difficulties in printing neural tissue: (i)   Acknowledgments
            the printing medium must have good cell viability and
            sufficient pores for nerve cells to extend and communicate;   We are grateful for the support of Life Science Institute of
            and (ii) it is necessary to print fine structures that can   Chongqing Medical University.


            Volume 9 Issue 5 (2023)                        103                         https://doi.org/10.18063/ijb.753
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