Zhang Jun, Xi Kun, Deng Guohua, Zou Xi, Lu Peirong
Department of Ophthalmology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215000, China.
Department of Ophthalmology, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, 300 Lanlin North Road, Changzhou 213000, China.
Gels. 2023 Aug 22;9(9):676. doi: 10.3390/gels9090676.
Ocular alkali burns recruit neutrophils and triggers neutrophil extracellular trap (NET)-neovascularization cascade effects that limit ocular surface reconstruction and functional repair. However, effective inhibition of the release of neutrophil extracellular traps after a corneal chemical injury, coordination of intrinsic immunity with corneal repair, and exploration of more effective and non-invasive drug-delivery modes are still urgently needed. Using an in vitro coculture system, we found that an alkaline environment stimulates neutrophils to release NETs, which can be regulated by deoxyribonuclease I (DNase I). Inspired by this, we loaded DNase I, which effectively regulates NETs, onto chitosan nanoparticles and combined them with silk fibroin to construct a composite hydrogel that can sustainably regulate NETs. The hydrogel reduced neutrophil extracellular trap production by 50% and neovascularization by approximately 70% through sustained DNase I release after a corneal alkali burn. The complex hydrogel promotes ocular surface reconstruction by modulating the intrinsic immune-cascade neovascularization effect, providing a new research basis for the construction of nanobiomaterials that modulate pathological neovascularization.
眼部碱烧伤会募集中性粒细胞并引发中性粒细胞胞外陷阱（NET）-新生血管形成级联效应，从而限制眼表重建和功能修复。然而，角膜化学伤后有效抑制中性粒细胞胞外陷阱的释放、协调固有免疫与角膜修复以及探索更有效且无创的给药方式仍亟待解决。利用体外共培养系统，我们发现碱性环境刺激中性粒细胞释放NETs，而这可由脱氧核糖核酸酶I（DNase I）调节。受此启发，我们将能有效调节NETs的DNase I负载到壳聚糖纳米颗粒上，并将其与丝素蛋白结合，构建出一种能持续调节NETs的复合水凝胶。角膜碱烧伤后，该水凝胶通过持续释放DNase I使中性粒细胞胞外陷阱生成减少50%，新生血管形成减少约70%。这种复合水凝胶通过调节固有免疫-级联新生血管形成效应促进眼表重建，为构建调节病理性新生血管形成的纳米生物材料提供了新的研究依据。
