Bacterial keratitis is one of the leading causes of blindness in the world. Frequent administration of antibiotic eye drops is the first-line treatment, which has difficulties in achieving favorable outcomes in some cases due to the emerging antibiotic resistance and low bioavailability. Antimicrobial peptides have been shown to overcome antibiotic resistance through diverse bactericidal mechanisms including antibiofilm effects, enabling them to be a promising strategy to combat resistance. Here, we report a novel antibacterial strategy with collagen nanosheets (CN) loaded with the cationic antimicrobial short peptide Tet213 (Tet213-CN). In this study, we demonstrated that Tet213-CN possessed excellent properties with good adherence, high oxygen permeability, transparency, biocompatibility, and showed no ocular irritation. In vitro and in vivo assays demonstrated that Tet213-CN had enhanced antibacterial and corneal epithelial healing effects. Furthermore, we observed that Tet213-CN treatment facilitated innate immune defense by promoting M1 macrophage polarization, increasing intracellular ROS generation and proinflammatory cytokine secretion, and enhancing phagocytosis of bacteria via the TLR2/MyD88/NF-κB signaling pathway. Most impressively, Tet213-CN achieved considerable outcomes in Pseudomonas aeruginosa keratitis models with a one-time application. Overall, Tet213-CN may serve as an ideal strategy in the management of bacterial keratitis, and shed new light onto the treatment against antibiotic-resistant bacteria. In addition, these results provide a conceptual framework for a novel macrophage-based strategy in the treatment of corneal infection diseases.

中文翻译：

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载有抗菌肽的胶原纳米片可增强细菌性角膜炎的抗菌活性、角膜伤口愈合和 M1 巨噬细胞极化

细菌性角膜炎是世界上导致失明的主要原因之一。频繁使用抗生素滴眼液是一线治疗方法，但由于抗生素耐药性的出现和生物利用度较低，在某些情况下很难取得良好的效果。抗菌肽已被证明可以通过包括抗菌膜效应在内的多种杀菌机制克服抗生素耐药性，使其成为对抗耐药性的有前景的策略。在这里，我们报告了一种新型抗菌策略，即胶原纳米片（CN）负载阳离子抗菌短肽Tet213（Tet213-CN）。在这项研究中，我们证明了Tet213-CN具有良好的粘附性、高透氧性、透明度、生物相容性和无眼部刺激等优异性能。体外和体内试验表明，Tet213-CN 具有增强抗菌和角膜上皮愈合作用。此外，我们观察到 Tet213-CN 治疗通过促进 M1 巨噬细胞极化、增加细胞内 ROS 生成和促炎细胞因子分泌以及通过 TLR2/MyD88/NF-κB 信号通路增强细菌吞噬作用来促进先天免疫防御。最令人印象深刻的是，Tet213-CN一次性应用在铜绿假单胞菌角膜炎模型中取得了可观的成果。总体而言，Tet213-CN可能作为治疗细菌性角膜炎的理想策略，并为抗生素耐药细菌的治疗提供新的思路。此外，这些结果为治疗角膜感染疾病的基于巨噬细胞的新型策略提供了概念框架。