AccScience Publishing / IJB / Volume 9 / Issue 3 / DOI: 10.18063/ijb.710
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ARTICLE

3D bioprinting as a prospective therapeutic strategy for corneal limbal epithelial stem cell deficiency

Qian Xue1,2† Liang Ma1,2† Hanyi Hu3,4 Qi Li1,2 Weiwei Wang3,4 Huayong Yang1,2 Bin Zhang1,2*
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1 State Key Laboratory of Fluid Power & Mechatronic Systems, Zhejiang University, Hangzhou, 310058, People’s Republic of China
2 School of Mechanical Engineering, Zhejiang University, Hangzhou, 310058, People’s Republic of China
3 School of Medicine, Zhejiang University, Hangzhou, 310058, People’s Republic of China
4 Department of Ophthalmology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310058, People’s Republic of China
Submitted: 21 October 2022 | Accepted: 23 November 2022 | Published: 15 March 2023
© 2023 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

Limbal epithelial stem cells (LESCs) are responsible for the maintenance and repair of the corneal surface. Injuries and diseases of the eye may result in a vision condition called limbal stem cell deficiency (LSCD). Without limbal stem cells, the cornea becomes opaque, vascularized, and inflamed. Cultured LESC therapy as a treatment method was first described in 1997, and LESCs cultured from either patients or donors have been used to treat LSCD successfully. However, the main source of cornea for LSCD treatment is from donors, which are too few to meet the demand (less than 1:70 of cases). The global shortage of donor cornea promotes the need for studies exploring corneal limbus alternatives. Many problems still remain unresolved, such as original geometry reconstruction, corneal epithelial regeneration, and ocular optical function restoration. 3D bioprinting has garnered tremendous attention in recent years, and significant advances have been made in fabricating cell–laden scaffolds. These advancements could lead to a promising treatment for LSCD. It is possible that alternative limbus stem cells can be constructed using 3D printing, which, in corneal limbus regeneration, enables personalized corneal implants and fabrication of single- or multilayer corneal limbus equivalents with corneal limbal stem cells. In this review, the progress, applications, and limitations of the most influential works regarding current treatments of LESC deficiency are discussed. The advantages of 3D bioprinting are illustrated, and some first promising steps toward the creation of a functional cornea limbus with 3D bioprinting are discussed. Finally, insights into the prospects and technical challenges facing the future research of 3D bioprinting of corneal limbus alternatives in vivo and in vitro are provided.

Keywords
3D bioprinting
Corneal limbus
Regenerative medicine
Limbal stem cell deficiency
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing