Guo Mengna, Wu Kai, Yang Mei, Yin Yue, Li Zhe, Wang Guoqing, Sun Jing, Fan Hongsong
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610065, Sichuan, PR China.
Department of Ophthalmology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610065, Sichuan, PR China.
Acta Biomater. 2025 Jul 1;201:198-211. doi: 10.1016/j.actbio.2025.05.054. Epub 2025 May 23.
Corneal alkali burns are a common ocular emergency that can lead to blindness, marked by inflammation and delayed epithelial healing due to elevated oxidative stress in the intraocular environment. Mitigating the levels of reactive oxygen species (ROS) and the inflammatory response is essential for developing corneal repair materials. Amniotic membrane (AM) is frequently employed for ocular surface repair but faces limitations such as limited availability and rapid degradation. This study developed a crosslinked decellularized bovine amniotic membrane (CAM) with high transparency, enhanced mechanical strength, and enzyme resistance. By introducing Manganese-based carbon dots (Mn CDs), the composite (CDs@CAM) retained the physical properties of CAM meanwhile brought in the multi-enzyme activities of Mn CDs. Extensive characterizations demonstrated CDs@CAM high CAT-like activity, SOD-like activity and scavenging ability of hydroxyl radical and nitrogen radical. Furthermore, cellular and animal experiments demonstrated that the CDs@CAM possessed good biocompatibility, strong antioxidant capabilities, and anti-inflammatory effects, and thus significantly promoted corneal epithelial regeneration, inhibited neovascularization, and prevented scarring in alkali burn repair. This study offers a feasible strategy for artificial corneas and corneal disease treatment. STATEMENT OF SIGNIFICANCE: In this study, we developed a crosslinked decellularized bovine amniotic membrane (CAM) integrated with manganese-based carbon dots (Mn CDs), creating a composite material (CDs@CAM) that addressed the issue of high oxidative stress and severe inflammation in the eye caused by corneal alkali burns. Different from the conventional amniotic membrane products, CDs@CAM retains advantageous physical properties and biocompatibility of CAM while offering potent antioxidant and anti-inflammatory capabilities. We confirmed its good biocompatibility, as well as reductions in intracellular ROS levels and inflammatory responses. Importantly, in an alkali-burned cornea model, we revealed its outstanding performance in promoting corneal epithelial repair, inhibiting neovascularization, and thus preventing scarring, restoring corneal thickness and clarity to normal levels.
角膜碱烧伤是一种常见的眼部急症，可导致失明，其特征是眼内环境中氧化应激升高，引发炎症和上皮愈合延迟。降低活性氧（ROS）水平和减轻炎症反应对于开发角膜修复材料至关重要。羊膜（AM）常用于眼表修复，但存在可用性有限和快速降解等局限性。本研究开发了一种具有高透明度、增强机械强度和酶抗性的交联脱细胞牛羊膜（CAM）。通过引入锰基碳点（Mn CDs），复合材料（CDs@CAM）保留了CAM的物理性质，同时具备了Mn CDs的多种酶活性。广泛的表征证明CDs@CAM具有高类过氧化氢酶活性、类超氧化物歧化酶活性以及对羟基自由基和氮自由基的清除能力。此外，细胞和动物实验表明，CDs@CAM具有良好的生物相容性、强大的抗氧化能力和抗炎作用，因此在碱烧伤修复中显著促进角膜上皮再生、抑制新生血管形成并防止瘢痕形成。本研究为人工角膜和角膜疾病治疗提供了一种可行的策略。重要意义声明：在本研究中，我们开发了一种与锰基碳点（Mn CDs）结合的交联脱细胞牛羊膜（CAM），制备出一种复合材料（CDs@CAM），解决了角膜碱烧伤引起的眼内高氧化应激和严重炎症问题。与传统羊膜产品不同，CDs@CAM保留了CAM的有利物理性质和生物相容性，同时具有强大的抗氧化和抗炎能力。我们证实了其良好的生物相容性，以及细胞内ROS水平和炎症反应的降低。重要的是，在碱烧伤角膜模型中，我们揭示了其在促进角膜上皮修复、抑制新生血管形成从而防止瘢痕形成、将角膜厚度和透明度恢复到正常水平方面的出色表现。
