集成式生物3D打印构建几何结构可控的角膜替代物方法（英文）

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

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。创新点: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。

Background: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.Objective:To overcome these limitations,in this paper,we present a novel integrated three-dimensional(3 D) bioprintingbased cornea substitute fabrication strategy to realize design,customized fabrication,and evaluation of multi-layer hollow structures with complicated surfaces.Methods:The key rationale for this method is to combine digital light processing(DLP) and extrusion bioprinting into an integrated 3 D 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.Results: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.Conclusions: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.