Hotaling Nathan A, Khristov Vladimir, Wan Qin, Sharma Ruchi, Jha Balendu Shekhar, Lotfi Mostafa, Maminishkis Arvydas, Simon Carl G, Bharti Kapil
1 Biosystems and Biomaterials Division, National Institute of Standards and Technology , Gaithersburg, Maryland.
2 Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health , Bethesda, Maryland.
J Ocul Pharmacol Ther. 2016 Jun;32(5):272-85. doi: 10.1089/jop.2015.0157. Epub 2016 Apr 25.
Clinical-grade manufacturing of a functional retinal pigment epithelium (RPE) monolayer requires reproducing, as closely as possible, the natural environment in which RPE grows. In vitro, this can be achieved by a tissue engineering approach, in which the RPE is grown on a nanofibrous biological or synthetic scaffold. Recent research has shown that nanofiber scaffolds perform better for cell growth and transplantability compared with their membrane counterparts and that the success of the scaffold in promoting cell growth/function is not heavily material dependent. With these strides, the field has advanced enough to begin to consider implementation of one, or a combination, of the tissue engineering strategies discussed herein. In this study, we review the current state of tissue engineering research for in vitro culture of RPE/scaffolds and the parameters for optimal scaffold design that have been uncovered during this research. Next, we discuss production methods and manufacturers that are capable of producing the nanofiber scaffolds in such a way that would be biologically, regulatory, clinically, and commercially viable. Then, a discussion of how the scaffolds could be characterized, both morphologically and mechanically, to develop a testing process that is viable for regulatory screening is performed. Finally, an example of a tissue-engineered RPE/scaffold construct is given to provide the reader a framework for understanding how these pieces could fit together to develop a tissue-engineered RPE/scaffold construct that could pass regulatory scrutiny and can be commercially successful.
功能性视网膜色素上皮（RPE）单层的临床级制造需要尽可能紧密地重现RPE生长的自然环境。在体外，可以通过组织工程方法实现这一点，即让RPE在纳米纤维生物或合成支架上生长。最近的研究表明，与膜状支架相比，纳米纤维支架在细胞生长和移植性方面表现更佳，并且支架在促进细胞生长/功能方面的成功并不严重依赖于材料。随着这些进展，该领域已经取得了足够的进步，开始考虑实施本文讨论的一种或多种组织工程策略。在本研究中，我们回顾了用于RPE/支架体外培养的组织工程研究的现状，以及在这项研究中发现的最佳支架设计参数。接下来，我们讨论能够以生物学、监管、临床和商业上可行的方式生产纳米纤维支架的生产方法和制造商。然后，讨论如何从形态学和力学方面对支架进行表征，以开发出一种适用于监管筛选的可行测试方法。最后，给出一个组织工程化RPE/支架构建体的示例，为读者提供一个框架，以理解这些部分如何组合在一起，从而开发出一个能够通过监管审查并取得商业成功的组织工程化RPE/支架构建体。
