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International Journal of Bioprinting                                  3D bioprinting for corneal regeneration




             Table 3. (Continued)
             Stroma    Corneal origin decellular-  Extrusion  Turbinate-   Good transparency, keratocytes   Rabbit  90,127,131,132
                       izes ECM bioink             derived mesenchy-  activated after transplantation
                                                   mal stem cells by
                                                   keratocyte induc-
                                                   tion
                       Alginate-nanocellu-  Extrusion  Human adipose   Good transparency, High viability,   No  94
                       lose-type I collagen        tissue-, bone mar-  ECM production
                       hydrogel                    row-, and corneal
                                                   stroma-derived
                                                   mesenchymal stem
                                                   cells
             Endothelium  Gelatin-RGD bioink;   Extrusion  Human corneal   No data        Rabbit   90,127,133
                       amniotic membrane           endothelial cells
                       decellularizes ECM
            Abbreviations: ECM: extracellular matrix; PCL: poly(caprolactone); PEG: poly(ethylene glycol); RGD: arginyl-glycyl-aspartic acid.

            to acknowledge the overarching challenge that currently   types and organs using 3D printing, such as the skin or
            there are no medical devices or Good Manufacturing   liver, underscoring the complexity of the field. 36,39
            Practice (GMP)-certified tissue printers capable of mass-  To date, stem cells or progenitor cells are the most
            producing artificial tissues with the requisite clinical and   commonly utilized cell types in research, primarily due to
            therapeutic quality. Consequently, only a fraction of the   their expansive differentiation potential and wound-healing
            localized and personalized therapeutic needs are presently   capabilities. The immunomodulation effect exhibited by
            met. These challenges underscore the need for continued   these cells further positions them to potentially mitigate
            advancements in technology and regulatory frameworks   inflammation during transplantation.
            to fully realize the potential of 3D bioprinting in meeting
            broader clinical demands for corneal regeneration.    The future commercialization of 3D-bioprinted
                                                               tissues necessitates the consideration of additional
            11. Conclusion                                     criteria, including the control of production processes,
                                                               standardization of protocols, cost-effectiveness, and
            Studies  revealed  that  3D  bioprinting  holds  significant   the logistics of manufactured products. For biological
            promise in advancing regenerative medicine research.   products, challenges related to storage and potential
            Among the myriad printing techniques available, extrusion   ethical considerations await resolution. However,
            processes predominate in research owing to their relative   ongoing research, in parallel with the development of
            cost-effectiveness. However, despite notable progress, tissue   3D-bioprinted tissues  in vitro and further investigations
            printing with 3D bioprinting remains in its nascent phases.   into in vivo applications, will collectively contribute to the
            While the majority of research focuses on developing   advancement of 3D bioprinting for clinical use. 90
            stromal substitutes, promising results are also emerging in
            the reconstruction of the epithelial and endothelial layers.
                                                               Acknowledgments
               Materials utilized in bioprinting must meet stringent
            criteria, encompassing bifunctionality, stability, and the   All  figures  were  generated  using  Biorender
            ability to foster appropriate biochemical and physiological   (www.app.biorender.com).
            interactions with cells. Equally critical is the requirement   Funding
            that these materials do not induce autoimmune reactions
            in the body. Frequently, 3D-printed cornea analogs   This work was supported by the National Research,
            are limited to using only one or two cell types and can   Development, and Innovation Office (NKFI PD 132570,
            successfully print in only one or two layers. Consequently,   awarded to Z.V.). Z.V. was also the recipient of the Bolyai
            artificial corneas fall short of wholly resembling native   János  Postdoctoral  Fellowship  (BO/00190/20/5),  funded
            tissue. An additional important consideration before   by the New National Excellence Program of the Hungarian
            clinical application revolves around  the challenges   Ministry for Innovation and Technology through the
            of vascularization and the implantation of artificially   National Research Development and Innovation Fund.
                         95
            produced tissue.  These issues are pervasive not only in   Projects TKP2021-EGA-28 and TKP2021-EGA-32 were
            artificial corneas but also in the exploration of other tissue   carried out with support from the Ministry of Innovation


            Volume 10 Issue 2 (2024)                       124                                doi: 10.36922/ijb.1669
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