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Abstract: Background: The shortage of donor corneas is a severe global issue, and hence the development of corneal alternatives is imperative and urgent. Although attempts to produce artificial cornea substitutes by tissue engineering have made some positive progress, many problems remain that hamper their clinical application worldwide. For example, the curvature of tissue-engineered cornea substitutes cannot be designed to fit the bulbus oculi of patients. Objective: To overcome these limitations, in this paper, we present a novel integrated three-dimensional (3D) bioprinting-based cornea substitute fabrication strategy to realize design, customized fabrication, and evaluation of multi-layer hollow structures with complicated surfaces. Methods: The key rationale for this method is to combine digital light processing (DLP) and extrusion bioprinting into an integrated 3D cornea bioprinting system. A designable and personalized corneal substitute was designed based on mathematical modelling and a computer tomography scan of a natural cornea. The printed corneal substitute was evaluated based on biomechanical analysis, weight, structural integrity, and fit. Results: The results revealed that the fabrication of high water content and highly transparent curved films with geometric features designed according to the natural human cornea can be achieved using a rapid, simple, and low-cost manufacturing process with a high repetition rate and quality. Conclusions: This study demonstrated the feasibility of customized design, analysis, and fabrication of a corneal substitute. The programmability of this method opens up the possibility of producing substitutes for other cornea-like shell structures with different scale and geometry features, such as the glomerulus, atrium, and oophoron.

集成式生物3D打印构建几何结构可控的角膜替代物方法

[1]Ahadian S, Khademhosseini A, 2018. A perspective on 3D bioprinting in tissue regeneration. Bio-Des Manuf, 1(3):157-160.

[2]Alaminos M, del Carmen Sánchez-Quevedo M, Muñoz-Ávila JI, et al., 2006. Construction of a complete rabbit cornea substitute using a fibrin-agarose scaffold. Invest Ophthalmol Vis Sci, 47(8):3311-3317.

[3]Bae H, Ahari AF, Shin H, et al., 2011. Cell-laden microengineered pullulan methacrylate hydrogels promote cell proliferation and 3D cluster formation. Soft Matter, 7(5):1903-1911.

[4]Burek H, Douthwaite WA, 1993. Mathematical models of the general corneal surface. Ophthalmic Physiol Opt, 13(1):68-72.

[5]Duarte Campos DF, Rohde M, Ross M, et al., 2019. Corneal bioprinting utilizing collagen-based bioinks and primary human keratocytes. J Biomed Mater Res Part A, 107(9):1945-1953.

[6]Fagerholm P, Lagali NS, Ong JA, et al., 2014. Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold. Biomaterials, 35(8):2420-2427.

[7]Gain P, Jullienne R, He ZG, et al., 2016. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol, 134(2):167-173.

[8]Gill EL, Li X, Birch MA, et al., 2018. Multi-length scale bioprinting towards simulating microenvironmental cues. Bio-Des Manuf, 1(2):77-88.

[9]Gullstrand A, 1910. The optical system of the eye. Physiol Opt, 1:350-358.

[10]Isaacson A, Swioklo S, Connon CJ, 2018. 3D bioprinting of a corneal stroma equivalent. Exp Eye Res, 173:188-193.

[11]Kiely PM, Smith G, Carney LG, 1982. The mean shape of the human cornea. Opt Acta: Int J Opt, 29(8):1027-1040.

[12]Kim H, Park MN, Kim J, et al., 2019. Characterization of cornea-specific bioink: high transparency, improved in vivo safety. J Tissue Eng, 10:1-12.

[13]Lawrence BD, Marchant JK, Pindrus MA, et al., 2009. Silk film biomaterials for cornea tissue engineering. Biomaterials, 30(7):1299-1308.

[14]Lawrence BD, Pan Z, Liu AH, et al., 2012. Human corneal limbal epithelial cell response to varying silk film geometric topography in vitro. Acta Biomater, 8(10):3732-3743.

[15]Levis HJ, Peh GSL, Toh KP, et al., 2012. Plastic compressed collagen as a novel carrier for expanded human corneal endothelial cells for transplantation. PLoS ONE, 7(11):e50993.

[16]Meek KM, Knupp C, 2015. Corneal structure and transparency. Prog Retin Eye Res, 49:1-16.

[17]Mi SL, Chen B, Wright B, et al., 2010. Ex vivo construction of an artificial ocular surface by combination of corneal limbal epithelial cells and a compressed collagen scaffold containing keratocytes. Tissue Eng Part A, 16(6):2091-2100.

[18]Na K, Shin S, Lee H, et al., 2018. Effect of solution viscosity on retardation of cell sedimentation in DLP 3D printing of gelatin methacrylate/silk fibroin bioink. J Ind Eng Chem, 61:340-347.

[19]Sasaki S, Funamoto S, Hashimoto Y, et al., 2009. In vivo evaluation of a novel scaffold for artificial corneas prepared by using ultrahigh hydrostatic pressure to decellularize porcine corneas. Mol Vis, 15:2022-2028.

[20]Taylor ZD, Garritano J, Sung S, et al., 2015. THz and mm-wave sensing of corneal tissue water content: electromagnetic modeling and analysis. IEEE Trans Terahertz Sci Technol, 5(2):170-183.

[21]Torricelli AAM, Wilson SE, 2014. Cellular and extracellular matrix modulation of corneal stromal opacity. Exp Eye Res, 129:151-160.

[22]Wang BH, Xu YS, Xie WJ, et al., 2018. Effects of corneal thickness distribution and apex position on postoperative refractive status after full-bed deep anterior lamellar keratoplasty. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(11):863-870.

[23]Ying GL, Jiang N, Yu CJ, et al., 2018. Three-dimensional bioprinting of gelatin methacryloyl (GelMA). Bio-Des Manuf, 1(4):215-224.

[24]Yoeruek E, Bayyoud T, Maurus C, et al., 2012. Decellularization of porcine corneas and repopulation with human corneal cells for tissue-engineered xenografts. Acta Ophthalmol, 90(2):e125-e131.

[25]Zhang B, Gao L, Gu L, et al., 2017. High-resolution 3D bioprinting system for fabricating cell-laden hydrogel scaffolds with high cellular activities. Procedia CIRP, 65: 219-224.

[26]Zhang B, Xue Q, Li JT, et al., 2019. 3D bioprinting for artificial cornea: challenges and perspectives. Med Eng Phys, 71: 68-78.