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构建功能集成的人工角膜基质替代物:具有基于胶原蛋白的多尺度仿生骨架的双面生物粘合剂植入物。

Engineering a functionality-integrated artificial cornea stromal Substitute: Janus bio-adhesive implant with a collagen-based multi-scale biomimetic skeleton.

作者信息

Lei Miao, Ji Yue, Zhang Shaohua, Hou Bing, Lu Yi, Sun Jianguo, Liu Changsheng, Qu Xue

机构信息

Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Eye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.

出版信息

Bioact Mater. 2025 Jun 24;51:740-757. doi: 10.1016/j.bioactmat.2025.06.030. eCollection 2025 Sep.


DOI:10.1016/j.bioactmat.2025.06.030
PMID:40641839
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12242454/
Abstract

Corneal transplantation presents an urgent demand for artificial cornea stromal substitutes (ACSs) with comprehensive functional design, spanning from material biology to clinical application. Here, we report the use of an engineering integration strategy to develop Janus ACSs with collagen-based multiscale biomimetic skeletons and tissue-adhesion. Specifically, the electro-assembly of collagen is employed to construct the skeleton of Janus ACS that mimics the microstructure and macroscopic morphology of native corneal stroma, ensuring the desired transparency, refractive power and adaptable shape. The bi-component "bio-cement" coating on the surface of skeleton, composed of 4-arm polyethylene glycol succinyl succinate and ε-polylysine, undergoes fast and mild amidation reactions driven by interfacial moisture, curing into a transparent hydrogel coating. The coating establishes a stable covalent connection between the corneal stroma and the skeleton, achieving immediate (<10 s) and stable tissue adhesion to adapt to the wet, dynamic mechanical environment of the eye. and in vivo studies further confirmed that the customized bio-adhesive Janus ACSs allow sutureless implantation and facilitate corneal epithelialization, stroma integration and reconstruction. A foraging behavior test highlighted the significant advantages of Janus ACSs in rapid vision recovery. The engineered integrated manufacturing of Janus ACSs potentially maximizes practicality while minimizing costs in applications.

摘要

角膜移植对具有全面功能设计的人工角膜基质替代物(ACSs)提出了迫切需求,其功能设计涵盖从材料生物学到临床应用的各个方面。在此,我们报告了一种工程集成策略的应用,以开发具有基于胶原蛋白的多尺度仿生骨架和组织粘附功能的双面ACSs。具体而言,采用胶原蛋白的电组装来构建双面ACS的骨架,该骨架模仿天然角膜基质的微观结构和宏观形态,确保所需的透明度、屈光力和可适应的形状。骨架表面由四臂聚乙二醇琥珀酸琥珀酸酯和ε-聚赖氨酸组成的双组分“生物水泥”涂层,在界面水分的驱动下发生快速温和的酰胺化反应,固化成透明水凝胶涂层。该涂层在角膜基质和骨架之间建立了稳定的共价连接,实现了即时(<10秒)且稳定的组织粘附,以适应眼睛湿润、动态的机械环境。体内研究进一步证实,定制的生物粘附双面ACSs允许无缝植入,并促进角膜上皮化、基质整合和重建。觅食行为测试突出了双面ACSs在快速视力恢复方面的显著优势。双面ACSs的工程集成制造在应用中可能最大限度地提高实用性,同时降低成本。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/502428bb4b59/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/2c1b601a9c48/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/0bb7040c0268/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/f13bc6746ed4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/83bde6abe0a5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/44128b54ae40/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/5c56a3728b1a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/a673358061b7/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/502428bb4b59/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/2c1b601a9c48/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/0bb7040c0268/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/f13bc6746ed4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/83bde6abe0a5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/44128b54ae40/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/5c56a3728b1a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/a673358061b7/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/12242454/502428bb4b59/gr6.jpg

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本文引用的文献

[1]
Swift Covalent Gelation Coupled with Robust Wet Adhesive Powder: A Novel Approach for Acute Massive Hemorrhage Control in Dynamic and High-Pressure Wound Environments.

Small. 2024-8

[2]
Corneal fibrosis: From in vitro models to current and upcoming drug and gene medicines.

Adv Drug Deliv Rev. 2024-6

[3]
Electro-Sorting Create Heterogeneity: Constructing A Multifunctional Janus Film with Integrated Compositional and Microstructural Gradients for Guided Bone Regeneration.

Adv Sci (Weinh). 2024-3

[4]
A suture-free, shape self-adaptive and bioactive PEG-Lysozyme implant for Corneal stroma defect repair and rapid vision restoration.

Bioact Mater. 2023-6-28

[5]
ECM-Like Adhesive Hydrogel for the Regeneration of Large Corneal Stromal Defects.

Adv Healthc Mater. 2023-8

[6]
A "T.E.S.T." hydrogel bioadhesive assisted by corneal cross-linking for in situ sutureless corneal repair.

Bioact Mater. 2023-2-11

[7]
Sutureless transplantation using a semi-interpenetrating polymer network bioadhesive for ocular surface reconstruction.

Acta Biomater. 2022-11

[8]
Delivery of Cells to the Cornea Using Synthetic Biomaterials.

Cornea. 2022-10-1

[9]
Natural Dual-Crosslinking Bioadhesive Hydrogel for Corneal Regeneration in Large-Size Defects.

Adv Healthc Mater. 2022-11

[10]
Electrical Signal Initiates Kinetic Assembly of Collagen to Construct Optically Transparent and Geometry Customized Artificial Cornea Substitutes.

ACS Nano. 2022-7-26

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