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RESEARCH ARTICLE
Fabrication of biomimetic corneas featuring epithelial, stromal, and endothelial layers via bioprinting
Tong Zhu1,2† ,
Renhao Ni1† ,
Haowen Sun1,3 ,
Shengkai Yu1 ,
Xu Cao1,4 ,
Shang Chen1 ,
Jingyu Shi4 ,
Cuicui Su1 ,
Yang Luo1,4* ,
Lu Yang2* ,
Hua Zhang1*
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1 Research Institute of Smart Medicine and Biological Engineering, Health Science Center, Ningbo University, Ningbo, Zhejiang,
China
2 Department of Ophthalmology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,
China
3 College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou,
China
4 Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,
China
†These authors contributed equally to this work.
IJB, 025380380 https://doi.org/10.36922/IJB025380380
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 gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA) composite hydrogel. The engineered scaffold successfully recapitulates the native cornea’s trilaminar architecture (epithelium, stroma, and endothelium) and exhibits 30–80% optical transparency across the visible spectrum. The hybrid hydrogel exhibits optimal wettability (a contact angle of approximately 50° and 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 revealed the phenotypic orientation of seeded cells toward key corneal lineages, with upregulation of epithelial (Klf4 and Pax6), stromal (Col1a1 and Col4a4), and endothelial (Zeb1 and Foxc1) markers. Overall, the bioprinted GelMA/HAMA biomimetic cornea presents a promising proof of concept for a trilayered tissue-engineered corneal construct.
Graphical abstract
Keywords
Biomimetic cornea
Hydrogel
Multi-cell types
Three-dimensional bioprinting
Tissue engineering
Funding
This research was supported by the Science and Technology Innovation 2035 Major Project of Ningbo (No. 2024Z212), the Ningbo Natural Science Foundation (No. 2022J121), Zhejiang Provincial Disease Prevention and Control Science and Technology Program (Grant No. 2025JK276) and the Key Laboratory of Polymeric Composite & Functional Materials of the Ministry of Education (No. PCFM-2025A02).
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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