Journal of Zhejiang University-SCIENCE B

, Volume 20, Issue 12, pp 945–959 | Cite as

Integrated 3D bioprinting-based geometry-control strategy for fabricating corneal substitutes

  • Bin Zhang
  • Qian Xue
  • Han-yi Hu
  • Meng-fei Yu
  • Lei Gao
  • Yi-chen Luo
  • Yang Li
  • Jin-tao Li
  • Liang MaEmail author
  • Yu-feng Yao
  • Hua-yong Yang



The shortage of donor corneas is a severe global issue, and hence the development of corneal alternatives is imperative and urgent. Although attempts to produce artificial cornea substitutes by tissue engineering have made some positive progress, many problems remain that hamper their clinical application worldwide. For example, the curvature of tissue-engineered cornea substitutes cannot be designed to fit the bulbus oculi of patients.


To overcome these limitations, in this paper, we present a novel integrated three-dimensional (3D) bioprinting-based cornea substitute fabrication strategy to realize design, customized fabrication, and evaluation of multi-layer hollow structures with complicated surfaces.


The key rationale for this method is to combine digital light processing (DLP) and extrusion bioprinting into an integrated 3D cornea bioprinting system. A designable and personalized corneal substitute was designed based on mathematical modelling and a computer tomography scan of a natural cornea. The printed corneal substitute was evaluated based on biomechanical analysis, weight, structural integrity, and fit.


The results revealed that the fabrication of high water content and highly transparent curved films with geometric features designed according to the natural human cornea can be achieved using a rapid, simple, and low-cost manufacturing process with a high repetition rate and quality.


This study demonstrated the feasibility of customized design, analysis, and fabrication of a corneal substitute. The programmability of this method opens up the possibility of producing substitutes for other cornea-like shell structures with different scale and geometry features, such as the glomerulus, atrium, and oophoron.

Key words

3D bioprinting Corneal alternative Digital light processing (DLP) Extrusion Geometry-control 

集成式生物3D 打印构建几何结构可控的角膜替 代物方法


目 的

供体角膜短缺是一个全球性问题。现有的角膜替 代物主要依赖于传统的组织工程制造方法, 仅支 持具有不可控曲率的平坦或弯曲膜的制备。我们 提出构建具有设计几何特征的弯曲薄膜, 以通过 生物3D 打印实现厚度及曲率半径可控的角膜替 代物。


提出一种集成的3D 角膜替代物打印系统, 为3D 角膜支架提供了一种新颖的制作方法; 提出角膜 光学特性与角膜支架几何特征的关系, 并分析影 响角膜光学功能的相关影响因素。根据扫描数 据, 采用该方法可以快速构建具有天然角膜几何 形状和尺度的角膜支架。使用该方法可获得具有 高细胞活力的载有细胞的复杂弯曲角膜状结构。 该方法具有低制造成本和高重复性, 是根据需要 快速构建角膜预替代物的有效方法。

方 法

通过建立角膜数学模型, 研究维持角膜视功能和 生理学的关键几何参数和其他主导因素; 根据天 然角膜的表面拓扑结构, 通过计算机辅助设计对 精确定制的人造角膜进行建模; 通过集成数字光 处理和挤出生物打印来制备用于角膜替代的曲 面薄膜。

结 论

由于结构可控性等优点, 生物3D 打印是制备具有 几何结构可控人工生物合成角膜的有效工具, 可 以个性化构建具有天然角膜尺度的角膜替代物。


生物3D 打印 角膜替代物 光固化打印 挤出 打印 结构控制 

CLC number

R779.65 Q819 


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Bin ZHANG, Qian XUE, Liang MA, and Han-yi HU planned the study and performed the experimental work and data analysis. Qian XUE wrote the manuscript. Meng-fei YU, Lei GAO, Yi-chen LUO, Yang LI, Jin-tao LI, Yu-feng YAO, and Hua-yong YANG assist in reviewing papers. All authors read and approved the final manuscript. Therefore, all authors had full access to all the data in the study and take responsibility for the integrity and security of the data.

Compliance with ethics guidelines

Bin ZHANG, Qian XUE, Han-yi HU, Meng-fei YU, Lei GAO, Yi-chen LUO, Yang LI, Jin-tao LI, Liang MA, Yu-feng YAO, and Hua-yong YANG declare that they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Fluid Power & Mechatronic SystemsZhejiang UniversityHangzhouChina
  2. 2.School of Mechanical EngineeringZhejiang UniversityHangzhouChina
  3. 3.Department of Ophthalmology, Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouChina
  4. 4.The Affiliated Stomatologic Hospital, School of MedicineZhejiang UniversityHangzhouChina

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