AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025380380
RESEARCH ARTICLE
Early Access

Fabrication of biomimetic corneas featuring epithelial, stromal, and endothelial layers via bioprinting

Tong Zhu1,2† Renhao Ni1† Haowen Sun1,3 Shengkai Yu1 Xu Cao1,2 Shang Chen1 Jingyu Shi2 Cuicui Su1 Yang Luo1,2* Lu Yang2* Hua Zhang1*
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1 Research Institute of Smart Medicine and Biological Engineering, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China
2 The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China
3 College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550025, China
†These authors contributed equally to this work.
Received: 15 September 2025 | Accepted: 12 December 2025 | Published online: 18 December 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

The bioengineering of full-thickness corneal substitutes presents significant challenges, primarily due to the complex stratified structure of the cornea, which consists of the epithelium, stroma, and endothelium, as well as its critical functional requirements, including optical transparency, mechanical stability, and biocompatibility. Herein, we present an integrated fabrication strategy that combines embedded hydrogel bioprinting with subsequent two-dimensional endothelial cell seeding to create biomimetic corneal structures using a GelMA/HAMA composite hydrogel. The engineered scaffold successfully recapitulates the native cornea's trilaminar architecture (epithelium, stroma, endothelium) and exhibits moderate 30–80% optical transparency across the visible spectrum. The hybrid hydrogel exhibits optimal wettability, a contact angle of approximately 50°, minimal swelling of less than 10%, and controlled degradation kinetics, effectively addressing the limitations of single-component hydrogels. The scaffold maintains structural integrity during suturing and supports robust cellular proliferation and migration. Gene expression analysis reveals the phenotypic orientation of seeded cells toward key corneal lineages, with upregulation of epithelial (KLF4, PAX6), stromal (COL1A1, COL4A4), and endothelial (ZEB1, FOXC1) markers. Overall, the bioprinted GelMA/HAMA biomimetic cornea presents a promising proof of concept for a trilayered tissue-engineered corneal construct.

Keywords
Biomimetic cornea
Hydrogel
3D bioprinting
Multi-cell types
Tissue engineering
Funding
This research was supported by the Science and Technology Innovation 2035 Major Project of Ningbo (2024Z212), the Ningbo Natural Science Foundation (2022J121), and the Key Laboratory of Polymeric Composite & Functional Materials of Ministry of Education (PCFM-2025A02).
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing