Oriented cellulose hydrogel:Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers  

作　　者：Lina Dong Zixin Fan Bixing Fang Xiaoyu Zhao Hongyi Yao Gangpei Cai Shuo Yang Guoming Zhang Xiaoqi Cheng Yun Feng Shengli Mi Wei Sun 

机构地区：[1]Tsinghua Shenzhen International Graduate School,Tsinghua University,Shenzhen,518055,China [2]Department of Burns,The Second Affiliated Hospital,Zhejiang University School of Medicine,Zhejiang,China [3]Shenzhen Eye Hospital,Jinan University,Shenzhen Eye Institute,Shenzhen,Guangdong,518040,China [4]Department of Otolaryngology,The Second Affiliated Hospital,Zhejiang University School of Medicine,Zhejiang,China [5]Department of Mechanical Engineering,Biomanufacturing Center,Tsinghua University,Beijing,China [6]Department of Mechanical Engineering,Drexel University,Philadelphia,PA,USA [7]Department of Ophthalmology,Peking University Third Hospital,Beijing,100191,China

出　　处：《Bioactive Materials》2024年第11期15-29,共15页生物活性材料（英文）

基　　金：Tsinghua Berkeley Shenzhen Institute and the Project of Basic Research of Shenzhen,China(JCYJ20170412101508433&JCYJ20180507183655307);National Key Research and Development Program of China(2023YFE0203100);National Natural Science Foundation of China(Grant Nos.82271051,82070926).

摘　　要：Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries.Corneal scars such as leukoplakia are formed due to inflammation,oxidative stress and non-directed repair,which seriously affect the patients'subsequent visual and life quality.In this study,drawing inspiration from the oriented structure of collagen fibers within the corneal stroma,we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning.It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer.The results showed that it effectively inhibited Candida albicans,Aspergillus Niger,Fusarium sapropelum,which mainly affects TNF,NF-kappa B,and HIF-1 signaling pathways,achieving effective antifungal functions.More importantly,the fibroblasts interacted with extracellular matrix(ECM)of corneal stroma through formation of focal adhesions,promoted the proliferation and directional migration of cells in vitro,induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo.This process is mainly associated with MYLK,MYL9,and ITGA3 molecules.Furthermore,the downregulation the growth factors TGF-βand PDGF-βinhibits myofibroblast development and reduces scar-type ECM production,thereby reducing corneal leukoplakia.It also activates the PI3K-AKT signaling pathway,promoting corneal healing.In conclusion,the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers,inhibits inflammation,eliminates reactive oxygen species,and reduces corneal leukoplakia,which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

关 键 词：Corneal leukoplakia Fungal corneal ulcers Oriented tissue regeneration Nanozyme Cellulose hydrogel 

分 类 号：R772.2[医药卫生—眼科]