Bioinspired Hyaluronic Acid-Based Hydrogel Fuels Bi-Directional Lung Organoid Maturation via PIEZO1 and ITGB1 Mediated Mechanosensation

被引：1

作者：

Zhang, Junyao ^{[1
,2
]}

Marciano, Daniele ^{[3
]}

Wang, Lei ^{[1
,2
]}

Wang, Weiwei ^{[2
]}

Gossen, Manfred ^{[2
]}

Yang, Mengting ^{[1
]}

Peng, Tingying ^{[4
]}

Gautrot, Julien ^{[3
]}

Xu, Xun ^{[2
]}

Ma, Nan ^{[1
,2
]}

机构：

[1] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany

[2] Inst Act Polymers, Helmholtz Zentrum Hereon, D-14513 Teltow, Germany

[3] Queen Mary Univ London, Sch Engn & Mat Sci, London E1 4NS, England

[4] Helmholtz Munich, Inst Computat Biol, D-85764 Neuherberg, Germany

来源：

ADVANCED MATERIALS INTERFACES | 2024年 / 11卷 / 28期

关键词：

biomechanics; hyaluronic acid (HA); hydrogel; lung organoid; piezo1; ACTOMYOSIN CONTRACTILITY; EPITHELIAL-CELLS; PROGENITOR CELLS; DIFFERENTIATION; GENERATION; REGENERATION; MECHANISMS; MODELS;

D O I：

10.1002/admi.202400194

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Lung diseases are one of the leading causes of global mortality. Advances in induced pluripotent stem cell (iPSC) differentiation have enabled the creation of bronchiolar and alveolar lung organoids, advancing research on lung conditions. Traditional Matrigel encapsulation, reliant on the spontaneous assembly and propagation of cells with limited external intervention, often results in variability and low reproducibility. The absence of hyaluronic acid (HA) in Matrigel, a key lung extracellular matrix component, limits bronchiolar and alveolar cell differentiation, reducing the efficacy and reproducibility of iPSC-derived organoid generation. To address this, a novel hybrid hydrogel combining HA and 23% Matrigel, inspired by the natural lung environment, is developed. This hydrogel offers improved biochemical support and viscoelastic properties, significantly accelerating organoid development. Within eight days, the hydrogel produces uniformly sized organoids containing both bronchiolar and alveolar epithelial cells. Increased levels of active mechanosensors and transducers, including PIEZO1, Integrin, and Myosin, suggest that the hydrogel's altered viscoelasticity triggers a mechanotransduction cascade. This bioinspired hydrogel provides a robust, fast model for biomedical research, facilitating rapid drug screening, respiratory disease treatment studies, and surfactant trafficking investigations. Furthermore, it enables the exploration of underlying biomechanical mechanisms to enhance the controllability of organoid generation and maturation. Advances in induced pluripotent stem cell (iPSC)-derived lung organoids aid hypoplasia, pathogenesis, and fibrosis studies. Conventional Matrigel culture lacks native lung properties, reducing reproducibility. A novel hydrogel containing the native lung matrix component hyaluronic acid (HA) accelerates organoid maturation, producing uniform bronchial and alveolar cells in eight days. This bioinspired approach may enhance biomedical research and speed up pharmaceutical development. image

引用

页数：13