Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA.
William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio, USA.
J Biomed Mater Res A. 2022 Oct;110(10):1621-1635. doi: 10.1002/jbm.a.37412. Epub 2022 May 23.
Many disease pathologies, particularly in the eye, are induced by oxidative stress. In particular, injury to the optic nerve (ON), or optic neuropathy, is one of the most common causes of vision loss. Traumatic optic neuropathy (TON) occurs when the ON is damaged following blunt or penetrating trauma to either the head or eye. Currently, there is no effective treatment for TON, only management options, namely the systematic delivery of corticosteroids and surgical decompression of the optic nerve. Unfortunately, neither option alleviates the generation of reactive oxygen species (ROS) which are responsible for downstream damage to the ON. Additionally, the systemic delivery of corticosteroids can cause fatal off-target effects in cases with brain involvement. In this study, we developed a tunable injectable hydrogel delivery system for local methylene blue (MB) delivery using an internal method of crosslinking. MB was chosen due to its ROS scavenging ability and neuroprotective properties. Our MB-loaded polymeric scaffold demonstrated prolonged release of MB as well as in situ gel formation. Additionally, following rheological characterization, these alginate hydrogels demonstrated minimal cytotoxicity to human retinal pigment epithelial cells in vitro and exhibited injection feasibility through small-gauge needles. Our chosen MB concentrations displayed a high degree of ROS scavenging following release from the alginate hydrogels, suggesting this approach may be successful in reducing ROS levels following ON injury, or could be applied to other ocular injuries.
许多疾病病理学，特别是眼部疾病，都是由氧化应激引起的。特别是视神经（ON）损伤，即视神经病变，是导致视力丧失的最常见原因之一。外伤性视神经病变（TON）是由于头部或眼部受到钝器或穿透性损伤后导致视神经受损而发生的。目前，TON 没有有效的治疗方法，只有管理选项，即系统给予皮质类固醇和视神经减压手术。不幸的是，这两种方法都不能减轻活性氧（ROS）的产生，ROS 是导致 ON 下游损伤的原因。此外，皮质类固醇的全身给药在涉及大脑的情况下会引起致命的脱靶效应。在这项研究中，我们使用内部交联方法开发了一种用于局部亚甲蓝（MB）递送的可调式可注射水凝胶递送系统。选择 MB 是因为它具有清除 ROS 的能力和神经保护特性。我们负载 MB 的聚合物支架表现出 MB 的延长释放以及原位凝胶形成。此外，在流变学特性分析之后，这些藻酸盐水凝胶在体外对人视网膜色素上皮细胞显示出最小的细胞毒性，并且可以通过小口径针头进行注射。从藻酸盐水凝胶释放后，我们选择的 MB 浓度表现出高度的 ROS 清除能力，这表明这种方法可能成功地降低 ON 损伤后的 ROS 水平，或者可以应用于其他眼部损伤。
