Development of Müller cell-based 3D biomimetic model using bioprinting technology.

Müller cells are the principal glial cells for the maintenance of structural stability and metabolic homeostasis in the human retina. Although various in vitro experiments using two-dimensional (2D) monolayer cell cultures have been performed, the results provided only limited results because of the lack of 3D structural environment and different cellular morphology. We studied a Müller cell-based 3D biomimetic model for use in experiments on the in vivo -like functions of Müller cells within the sensory retina. Isolated primary Müller cells were bioprinted and a 3D-aligned architecture was induced, which aligned Müller cell structure in retinal tissue. The stereographic and functional characteristics of the biomimetic model were investigated and compared to those of the conventional 2D cultured group. The results showed the potential to generate Müller cell-based biomimetic models with characteristic morphological features such as endfeet, soma, and microvilli. Especially, the 3D Müller cell model under hyperglycemic conditions showed similar responses as observed in the in vivo diabetic model with retinal changes, whereas the conventional 2D cultured group showed different cytokine and growth factor secretions. These results show that our study is a first step toward providing advanced tools to investigate the in vivo function of Müller cells and to develop complete 3D models of the vertebrate retina.