A bilayer photoreceptor‐retinal tissue model with gradient cell density design: A study of microvalve‐based bioprinting

ARPE‐19 and Y79 cells were precisely and effectively delivered to form an in vitro retinal tissue model via 3D cell bioprinting technology. The samples were characterized by cell viability assay, haematoxylin and eosin and immunofluorescent staining, scanning electrical microscopy and confocal microscopy, and so forth. The bioprinted ARPE‐19 cells formed a high‐quality cell monolayer in 14 days. Manually seeded ARPE‐19 cells were poorly controlled during and after cell seeding, and they aggregated to form uneven cell layer. The Y79 cells were subsequently bioprinted on the ARPE‐19 cell monolayer to form 2 distinctive patterns. The microvalve‐based bioprinting is efficient and accurate to build the in vitro tissue models with the potential to provide similar pathological responses and mechanism to human diseases, to mimic the phenotypic endpoints that are comparable with clinical studies, and to provide a realistic prediction of clinical efficacy.

[1]  S. D. Carlson,et al.  The Photoreceptor Cells , 1984 .

[2]  B. Schlosshauer,et al.  In vitro model of the outer blood-retina barrier. , 2004, Brain research. Brain research protocols.

[3]  Activin Inhibits Cell Growth and Induces Differentiation in Human Retinoblastoma Y79 Cells , 2009, Current eye research.

[4]  Club Jules Gonin,et al.  Graefe's archive for clinical and experimental ophthalmology , 1982 .

[5]  P. Walter,et al.  The in vitro and in vivo behaviour of retinal pigment epithelial cells cultured on ultrathin collagen membranes. , 2009, Biomaterials.

[6]  Sailesh Kumar,et al.  Reducing the risk of fetal distress with sildenafil study (RIDSTRESS): a double-blind randomised control trial , 2016, Journal of Translational Medicine.

[7]  A. Mikos,et al.  Retinal pigment epithelial cell function on substrates with chemically micropatterned surfaces. , 1999, Biomaterials.

[8]  Jianzhong Fu,et al.  Bone regeneration in 3D printing bioactive ceramic scaffolds with improved tissue/material interface pore architecture in thin-wall bone defect , 2017, Biofabrication.

[9]  P. Adamson,et al.  Basement membrane-dependent modification of phenotype and gene expression in human retinal pigment epithelial ARPE-19 cells. , 2004, Investigative ophthalmology & visual science.

[10]  H. Rodemann,et al.  Establishment of a novel retinoblastoma (Rb) nude mouse model by intravitreal injection of human Rb Y79 cells – comparison of in vivo analysis versus histological follow up , 2016, Biology Open.

[11]  Takashi Kojima,et al.  Transmembrane proteins of tight junctions. , 2008, Biochimica et biophysica acta.

[12]  Z. Ahmed,et al.  Animal models of retinal injury. , 2012, Investigative ophthalmology & visual science.

[13]  R. L. Font,et al.  Immunohistochemical Demonstration of Neuronal and Astrocytic Differentiation in Retinoblastoma , 1985 .

[14]  J. Jonas,et al.  Count and density of human retinal photoreceptors , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.

[15]  G. Seigel,et al.  Comparison of mature retinal marker expression in Y79 and WERI-RB27 human retinoblastoma cell lines , 2012 .

[16]  G. Chader Multipotential differentiation of human Y-79 retinoblastoma cells in attachment culture. , 1987, Cell differentiation.

[17]  H. Tähti,et al.  Toxicity of Selected Cationic Drugs in Retinoblastomal Cultures and in Cocultures of Retinoblastomal and Retinal Pigment Epithelial Cell Lines , 2004, Neurochemical Research.

[18]  May Win Naing,et al.  Polyvinylpyrrolidone-Based Bio-Ink Improves Cell Viability and Homogeneity during Drop-On-Demand Printing , 2017, Materials.

[19]  Kang Zhang,et al.  3D printing of functional biomaterials for tissue engineering. , 2016, Current opinion in biotechnology.

[20]  G. Chader,et al.  Morphologic description of Y79 retinoblastoma cells by a simple image analysis system , 1990, In Vitro Cellular & Developmental Biology.

[21]  Wei Zhu,et al.  Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. , 2017, Biomaterials.

[22]  G. Whitesides,et al.  Patterning proteins and cells using soft lithography. , 1999, Biomaterials.

[23]  Peter C. Searson,et al.  In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform , 2016, Front. Bioeng. Biotechnol..

[24]  M. Simon,et al.  Cone cell-specific genes expressed in retinoblastoma. , 1988, Science.

[25]  M. Pennesi,et al.  Animal models of age related macular degeneration. , 2012, Molecular aspects of medicine.

[26]  G. Seigel,et al.  Differentiation of Y79 retinoblastoma cells induced by succinylated concanavalin A. , 1993, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[27]  R. Vento,et al.  Differentiation of Y79 cells induced by prolonged exposure to insulin , 1997, Molecular and Cellular Biochemistry.

[28]  S. Kaliki,et al.  Animal models in retinoblastoma research. , 2013, Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society.

[29]  Huifang Zhou,et al.  Recent advances in bioprinting techniques: approaches, applications and future prospects , 2016, Journal of Translational Medicine.

[30]  Wai Yee Yeong,et al.  Microvalve-based bioprinting - process, bio-inks and applications. , 2017, Biomaterials science.

[31]  Minhwan Chung,et al.  Wet‐AMD on a Chip: Modeling Outer Blood‐Retinal Barrier In Vitro , 2018, Advanced healthcare materials.

[32]  L. Leach,et al.  Establishment of a human in vitro model of the outer blood–retinal barrier , 2007, Journal of anatomy.

[33]  A. F. Wiechmann Recoverin in Cultured Human Retinoblastoma Cells: Enhanced Expression During Morphological Differentiation , 1996, Journal of neurochemistry.

[34]  M. Naash,et al.  Expression of cone-photoreceptor-specific antigens in a cell line derived from retinal tumors in transgenic mice. , 2004, Investigative ophthalmology & visual science.

[35]  S. Patil,et al.  Retinoblastoma Y79 cell line: A study of membrane structures , 1979, Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie.

[36]  L. Rizzolo Barrier properties of cultured retinal pigment epithelium. , 2014, Experimental eye research.

[37]  B. Ruggeri,et al.  Animal models of human disease: challenges in enabling translation. , 2014, Biochemical pharmacology.

[38]  F. Giordano,et al.  Use of the ARPE-19 cell line as a model of RPE polarity: basolateral secretion of FGF5. , 1998, Investigative ophthalmology & visual science.

[39]  Utkan Demirci,et al.  Cell encapsulating droplet vitrification. , 2007, Lab on a chip.

[40]  X. Illa,et al.  A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood-retinal barrier. , 2018, Lab on a chip.

[41]  M. Mandai,et al.  Retinal regeneration by transplantation of retinal tissue derived from human embryonic or induced pluripotent stem cells , 2016, Inflammation and Regeneration.

[42]  G. Chader,et al.  Behavior of human retinoblastoma cells in tissue culture , 1987 .

[43]  Chee Kai Chua,et al.  Bioprinting: Principles and Applications , 2015 .

[44]  Hyeong-Jin Lee,et al.  Recent cell printing systems for tissue engineering , 2017, International journal of bioprinting.

[45]  S. Bent,et al.  Thin collagen film scaffolds for retinal epithelial cell culture. , 2007, Biomaterials.

[46]  A. Di Polo,et al.  Rod photoreceptor-specific gene expression in human retinoblastoma cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[47]  J. Stone,et al.  Combining Neuroprotectants in a Model of Retinal Degeneration: No Additive Benefit , 2014, PloS one.

[48]  Sahar Javaherian,et al.  A Fast and Accessible Methodology for Micro-Patterning Cells on Standard Culture Substrates Using Parafilm™ Inserts , 2011, PloS one.

[49]  A. Lotery,et al.  Optimisation of polymer scaffolds for retinal pigment epithelium (RPE) cell transplantation , 2009, British Journal of Ophthalmology.

[50]  Irina Klimanskaya,et al.  Retinal pigment epithelium. , 2006, Methods in enzymology.

[51]  Wai Yee Yeong,et al.  Design and Printing Strategies in 3D Bioprinting of Cell‐Hydrogels: A Review , 2016, Advanced healthcare materials.

[52]  C. Chiba The retinal pigment epithelium: an important player of retinal disorders and regeneration. , 2014, Experimental eye research.

[53]  Barbara Rothen-Rutishauser,et al.  Engineering an in vitro air-blood barrier by 3D bioprinting , 2015, Scientific Reports.

[54]  S. Retterer,et al.  The effect of retinal pigment epithelial cell patch size on growth factor expression. , 2014, Biomaterials.

[55]  Xiulan Zhang,et al.  3D Printing: Print the future of ophthalmology. , 2014, Investigative ophthalmology & visual science.

[56]  May Win Naing,et al.  Skin Bioprinting: Impending Reality or Fantasy? , 2016, Trends in biotechnology.

[57]  L. Hjelmeland,et al.  ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. , 1996, Experimental eye research.

[58]  T. Reh,et al.  Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. , 2009, Cell stem cell.

[59]  T. Triche,et al.  Retinoblastoma—origin from a primitive neuroectodermal cell? , 1984, Nature.

[60]  Shu-zhen Wang,et al.  The Retinal Pigment Epithelium: a Convenient Source of New Photoreceptor cells? , 2014, Journal of ophthalmic & vision research.

[61]  I. Hutchings,et al.  Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing , 2013, Biofabrication.

[62]  D. Albert,et al.  Characteristics of an established cell line of retinoblastoma. , 1974, Journal of the National Cancer Institute.

[63]  Gordon G. Wallace,et al.  Biofabrication: an overview of the approaches used for printing of living cells , 2013, Applied Microbiology and Biotechnology.

[64]  T. Chirila,et al.  The cultivation of human retinal pigment epithelial cells on Bombyx mori silk fibroin. , 2012, Biomaterials.