Kim Jongmin, Kong Jeong Sik, Kim Hyeonji, Jo Yeonggwon, Cho Dong-Woo, Jang Jinah
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 37673, Republic of Korea.
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 37673, Republic of Korea.
Adv Healthc Mater. 2022 Dec;11(24):e2200728. doi: 10.1002/adhm.202200728. Epub 2022 Jul 27.
The retinal pigment epithelium (RPE) not only forms the outer blood-retinal barrier (oBRB) but also plays a multifunctional role in the ocular system. The loss of this epithelium leads to serious diseases resulting in vision impairment. No effective treatment is available for the repair of RPE damage. A functional in vitro RPE model that allows the recapitulation of oBRB-related pathophysiological responses is lacking. Here, a hybrid membrane printing technology is developed to fabricate cellular monolayers on the basement membrane to mimic human Bruch's membrane (BM). Using this technology, in vitro oBRB model containing the RPE monolayer on the printed BM with stable mechanical properties and fibril diameter similar to that of natural BM is developed. Compared to traditional collagen bioink, BM-based bioink significantly promotes RPE functions in vitro. Finally, smoking-like conditions are exposed to the model to recapitulate the absorption of mainstream cigarette smoke which is known as one of the risk factors for the disease progression. RPE function is damaged due to oxidative stress. Furthermore, the versatility of the model as a drug-testing platform is confirmed by the suppression of oxidative stress via antioxidants. This technology shows potential for fabricating a functional oBRB model that reflects patient conditions.
视网膜色素上皮（RPE）不仅构成了外血视网膜屏障（oBRB），还在眼系统中发挥着多功能作用。这种上皮细胞的丧失会导致严重疾病，进而导致视力损害。目前尚无有效的治疗方法来修复RPE损伤。缺乏一种能够重现与oBRB相关的病理生理反应的功能性体外RPE模型。在此，开发了一种混合膜打印技术，用于在基底膜上制造细胞单层，以模拟人布鲁赫膜（BM）。利用该技术，开发了一种体外oBRB模型，该模型在打印的BM上含有RPE单层，其机械性能稳定，纤维直径与天然BM相似。与传统的胶原蛋白生物墨水相比，基于BM的生物墨水在体外显著促进RPE功能。最后，将类似吸烟的条件施加于该模型，以重现主流香烟烟雾的吸收情况，而主流香烟烟雾是疾病进展的危险因素之一。由于氧化应激，RPE功能受损。此外，通过抗氧化剂抑制氧化应激证实了该模型作为药物测试平台的多功能性。该技术显示出制造反映患者状况的功能性oBRB模型的潜力。
