Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.
Int J Mol Sci. 2021 Jan 22;22(3):1095. doi: 10.3390/ijms22031095.
Retinal pigment epithelium (RPE) is a monolayer of the pigmented cells that lies on the thin extracellular matrix called Bruch's membrane. This monolayer is the main component of the outer blood-retinal barrier (BRB), which plays a multifunctional role. Due to their crucial roles, the damage of this epithelium causes a wide range of diseases related to retinal degeneration including age-related macular degeneration, retinitis pigmentosa, and Stargardt disease. Unfortunately, there is presently no cure for these diseases. Clinically implantable RPE for humans is under development, and there is no practical examination platform for drug development. Here, we developed porcine Bruch's membrane-derived bioink (BM-ECM). Compared to conventional laminin, the RPE cells on BM-ECM showed enhanced functionality of RPE. Furthermore, we developed the Bruch's membrane-mimetic substrate (BMS) via the integration of BM-ECM and 3D printing technology, which revealed structure and extracellular matrix components similar to those of natural Bruch's membrane. The developed BMS facilitated the appropriate functions of RPE, including barrier and clearance functions, the secretion of anti-angiogenic growth factors, and enzyme formation for phototransduction. Moreover, it could be used as a basement frame for RPE transplantation. We established BMS using 3D printing technology to grow RPE cells with functions that could be used for an in vitro model and RPE transplantation.
视网膜色素上皮（RPE）是一层位于称为布鲁赫膜的薄细胞外基质上的色素细胞。这单层是外层血视网膜屏障（BRB）的主要组成部分，具有多种功能。由于其关键作用，该上皮的损伤会导致广泛的与视网膜变性相关的疾病，包括年龄相关性黄斑变性、色素性视网膜炎和斯塔加特病。不幸的是，目前这些疾病尚无治愈方法。目前正在开发用于人类的临床可植入 RPE，并且没有用于药物开发的实用检查平台。在这里，我们开发了猪布鲁赫膜衍生的生物墨水（BM-ECM）。与传统的层粘连蛋白相比，BM-ECM 上的 RPE 细胞表现出增强的 RPE 功能。此外，我们通过整合 BM-ECM 和 3D 打印技术开发了类似于天然布鲁赫膜的结构和细胞外基质成分的布鲁赫膜模拟底物（BMS）。开发的 BMS 促进了 RPE 的适当功能，包括屏障和清除功能、抗血管生成生长因子的分泌以及光转导的酶形成。此外，它可用作 RPE 移植的基底框架。我们使用 3D 打印技术建立了 BMS，以培养具有可用于体外模型和 RPE 移植的功能的 RPE 细胞。
