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Artificial Meshed Vessel-Induced Dimensional Breaking Growth of Human Brain Organoids and Multiregional Assembloids
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-13 , DOI: 10.1021/acsnano.4c07844 Lei Xu 1, 2, 3 , Haibo Ding 1 , Shanshan Wu 2, 3, 4 , Nankun Xiong 1 , Yuan Hong 2, 3, 4 , Wanying Zhu 2, 3, 4 , Xingyi Chen 2, 3, 4 , Xiao Han 2, 3, 4 , Mengdan Tao 1 , Yuanhao Wang 2, 3, 4 , Da Wang 2, 3, 4 , Min Xu 2, 3, 4 , Da Huo 5 , Zhongze Gu 1 , Yan Liu 1, 2, 3, 4
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-13 , DOI: 10.1021/acsnano.4c07844 Lei Xu 1, 2, 3 , Haibo Ding 1 , Shanshan Wu 2, 3, 4 , Nankun Xiong 1 , Yuan Hong 2, 3, 4 , Wanying Zhu 2, 3, 4 , Xingyi Chen 2, 3, 4 , Xiao Han 2, 3, 4 , Mengdan Tao 1 , Yuanhao Wang 2, 3, 4 , Da Wang 2, 3, 4 , Min Xu 2, 3, 4 , Da Huo 5 , Zhongze Gu 1 , Yan Liu 1, 2, 3, 4
Affiliation
Brain organoids are widely used to model brain development and diseases. However, a major challenge in their application is the insufficient supply of oxygen and nutrients to the core region, restricting the size and maturation of the organoids. In order to vascularize brain organoids and enhance the nutritional supply to their core areas, two-photon polymerization (TPP) 3D printing is employed to fabricate high-resolution meshed vessels in this study. These vessels made of photoresist with densely distributed micropores with a diameter of 20 μm on the sidewall, are cocultured with brain organoids to facilitate the diffusion of culture medium into the organoids. The vascularized organoids exhibit dimensional breaking growth and enhanced proliferation, reduced hypoxia and apoptosis, suggesting that the 3D-printed meshed vessels partially mimic vascular function to promote the culture of organoids. Furthermore, cortical, striatal and medial ganglionic eminence (MGE) organoids are respectively differentiated to generate Cortico-Striatal-MGE assembloids by 3D-printed vessels. The enhanced migration, projection and excitatory signaling transduction are observed between different brain regional organoids in the assembloids. This study presents an approach using TPP 3D printing to construct vascularized brain organoids and assembloids for enhancing the development and assembly, offering a research model and platform for neurological diseases.
中文翻译:
人工网状容器诱导人脑类器官和多区域组合体的维度断裂生长
脑类器官广泛用于模拟大脑发育和疾病。然而,其应用中的一个主要挑战是核心区域的氧气和营养供应不足,限制了类器官的大小和成熟。为了使大脑类器官血管化并增强其核心区域的营养供应,本研究采用双光子聚合(TPP)3D打印来制造高分辨率网状血管。这些由光刻胶制成的血管,侧壁上有密集分布的直径为20μm的微孔,与脑类器官共培养,以促进培养基扩散到类器官中。血管化类器官表现出维度破坏性生长、增殖增强、缺氧和细胞凋亡减少,这表明 3D 打印的网状血管部分模仿血管功能,以促进类器官的培养。此外,通过 3D 打印血管分别分化皮质、纹状体和内侧神经节隆起 (MGE) 类器官,生成皮质-纹状体-MGE 组合体。在组合体中的不同脑区域类器官之间观察到增强的迁移、投射和兴奋性信号转导。本研究提出了一种使用TPP 3D打印构建血管化脑类器官和组合体的方法,以增强发育和组装,为神经系统疾病提供研究模型和平台。
更新日期:2024-09-13
中文翻译:
人工网状容器诱导人脑类器官和多区域组合体的维度断裂生长
脑类器官广泛用于模拟大脑发育和疾病。然而,其应用中的一个主要挑战是核心区域的氧气和营养供应不足,限制了类器官的大小和成熟。为了使大脑类器官血管化并增强其核心区域的营养供应,本研究采用双光子聚合(TPP)3D打印来制造高分辨率网状血管。这些由光刻胶制成的血管,侧壁上有密集分布的直径为20μm的微孔,与脑类器官共培养,以促进培养基扩散到类器官中。血管化类器官表现出维度破坏性生长、增殖增强、缺氧和细胞凋亡减少,这表明 3D 打印的网状血管部分模仿血管功能,以促进类器官的培养。此外,通过 3D 打印血管分别分化皮质、纹状体和内侧神经节隆起 (MGE) 类器官,生成皮质-纹状体-MGE 组合体。在组合体中的不同脑区域类器官之间观察到增强的迁移、投射和兴奋性信号转导。本研究提出了一种使用TPP 3D打印构建血管化脑类器官和组合体的方法,以增强发育和组装,为神经系统疾病提供研究模型和平台。