Multiplexed self-adaptable Janus hydrogels rescue epithelial malfunction to promote complete trachea repair

Yi Chen, Hai Tang, Yan Zhang, Lei Wang, Jun Zhu, Lele Wang, Anqi Li, Xiang Zeng, Binyu Yin, Yu Liang, Xiulin Dong, Qingfeng Bai, Ziyin Pan, Long Wang, Lei Zhang, Minglei Yang, Yunlang She, Weiyan Sun (), Kun Zhang () and Chang Chen ()
Additional contact information
Yi Chen: School of Medicine, Tongji University
Hai Tang: School of Medicine, Tongji University
Yan Zhang: University of Electronic Science and Technology of China
Lei Wang: School of Medicine, Tongji University
Jun Zhu: Tsinghua University
Lele Wang: Tongji University School of Medicine
Anqi Li: Tongji University School of Medicine
Xiang Zeng: Fudan University
Binyu Yin: University of Electronic Science and Technology of China
Yu Liang: University of Electronic Science and Technology of China
Xiulin Dong: University of Electronic Science and Technology of China
Qingfeng Bai: School of Medicine, Tongji University
Ziyin Pan: School of Medicine, Tongji University
Long Wang: School of Medicine, Tongji University
Lei Zhang: School of Medicine, Tongji University
Minglei Yang: Ningbo No.2 Hospital
Yunlang She: School of Medicine, Tongji University
Weiyan Sun: School of Medicine, Tongji University
Kun Zhang: University of Electronic Science and Technology of China
Chang Chen: School of Medicine, Tongji University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Epithelial malfunction rescue is the decisive step involved in complete trachea repair; however, this step remains challenging due to the harsh tracheal environment and unclear pathogenesis, which still made current bioengineered trachea transplants receive fatal complications. Herein, bacterial infection-induced neutrophilic oxidative stress imbalance and epithelial stemness loss were identified as the pathogenic factors. Targeting pathogenesis, multiplexed hydrogels with adhesive and anti-fouling Janus sides, anti-swelling and anti-bacteria properties are constructed to adapt in mucous and causative agent-rich trachea environments. In two epithelial injury models and two tracheal transplantation-related epithelial deficiency models, the hydrogels blockade oxidative stress-innate immune cascade axis, reactivate epithelial mucociliary regenerative ability to rescue epithelial malfunction with stenosis-free mucociliary epithelium regeneration. Importantly, the versatility of hydrogel is validated via its integration with routine bioengineered vascular and cartilage transplants, wherein the regenerated pseudostratification epithelium, cartilage and vascularization resemble native-like trachea, resulting in the complete tracheal repair including structure and respiratory function reinvigoration. Our research provides insights into epithelial interface diseases and guides related biomaterials design.

Date: 2025
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DOI: 10.1038/s41467-025-61135-z

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