Engineered micro-structured biomimetic material for modelling the outer blood-retinal barrier

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-04-23 DOI:10.1016/j.biomaterials.2025.123357

Chloé Dujardin , Walter Habeler , Paola Aprile , Alessandra Dellaquila , Christelle Monville , Didier Letourneur , Teresa Simon-Yarza

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Abstract

The outer blood-retinal barrier (oBRB) is compromised in several retinal pathologies, such as age-related macular degeneration affecting over 200 million people worldwide. This 200–350 μm thick tissue includes the retinal pigment epithelium (RPE), the Bruch's membrane, and the vascularized choroid supplying the outer retina. Degeneration of the RPE and/or choroid leads to photoreceptor loss and, ultimately, blindness. Current in vitro co-culture oBRB models developed to better understand the diseases and to propose therapeutic alternatives are often simplistic, focusing on 2D cultures, or face limitations including non-physiological dimensions or low throughput.

This study presents an innovative scaffold-driven approach to model the oBRB using a polysaccharide membrane engineered by freeze-drying. Our specific protocol allowed to mimic the oBRB structure, within physiological dimensions, generating a non-porous surface to culture the hiPSC-derived RPE monolayer, and an internal 3D porous structure for the choroidal network. Results showed that the inner porous structure promoted physiological self-organization of endothelial cells and pericytes. Our single-piece functional material allowed the cultivation of both RPE and choroidal compartments in close proximity, favoring cellular interactions, while maintaining them in their designated locations. This cyto-compatible, easy-to-use, and off-the-shelf membrane, produced at large amounts and low costs, provides a physiologically relevant biomaterial for oBRB tissue modelling.

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用于模拟血液-视网膜外屏障的工程微结构仿生材料

外血视网膜屏障（oBRB）在几种视网膜病变中受损，例如影响全球超过2亿人的年龄相关性黄斑变性。这个200-350 μm厚的组织包括视网膜色素上皮（RPE）、布鲁氏膜和供应外视网膜的血管化脉络膜。RPE和/或脉络膜的退化导致光感受器丧失，最终导致失明。目前为更好地了解疾病和提出治疗方案而开发的体外共培养oBRB模型通常过于简单，侧重于2D培养，或者面临包括非生理维度或低通量在内的限制。本研究提出了一种创新的支架驱动方法，利用冷冻干燥的多糖膜来模拟oBRB。我们的特定方案允许在生理尺寸内模拟oBRB结构，生成无孔表面来培养hipsc衍生的RPE单层，以及用于脉络膜网络的内部3D多孔结构。结果表明，内部多孔结构促进了内皮细胞和周细胞的生理自组织。我们的单片功能材料允许近距离培养RPE和脉络膜隔室，有利于细胞相互作用，同时将它们保持在指定位置。这种细胞兼容，易于使用，现成的膜，大量生产和低成本，为oBRB组织建模提供了生理相关的生物材料。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.