Artificial Meshed Vessel-Induced Dimensional Breaking Growth of Human Brain Organoids and Multiregional Assembloids

被引:13
作者
Xu, Lei [1 ,2 ,3 ,4 ]
Ding, Haibo [1 ,2 ]
Wu, Shanshan [3 ,4 ,5 ]
Xiong, Nankun [1 ,2 ]
Hong, Yuan [3 ,4 ,5 ]
Zhu, Wanying [3 ,4 ,5 ]
Chen, Xingyi [3 ,4 ,5 ]
Han, Xiao [3 ,4 ,5 ]
Tao, Mengdan [1 ,2 ]
Wang, Yuanhao [3 ,4 ,5 ]
Wang, Da [3 ,4 ,5 ]
Xu, Min [3 ,4 ,5 ]
Huo, Da [6 ]
Gu, Zhongze [1 ,2 ]
Liu, Yan [1 ,2 ,3 ,4 ,5 ]
机构
[1] Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Digital Med Engn, Nanjing 210096, Peoples R China
[2] Southeast Univ, Zhongda Hosp, Dept Neurol, Nanjing 210096, Peoples R China
[3] Nanjing Med Univ, State Key Lab Reprod Med & Offspring Hlth, Nanjing 211166, Peoples R China
[4] Nanjing Med Univ, Inst Stem Cell & Neural Regenerat, Sch Pharm, Nanjing 211166, Peoples R China
[5] Nanjing Med Univ, Collaborat Innovat Ctr Cardiovasc Dis Translat Med, Key Lab Targeted Intervent Cardiovasc Dis, Nanjing 211166, Peoples R China
[6] Nanjing Med Univ, Sch Pharm, Key Lab Cardiovasc & Cerebrovasc Med, Nanjing 211166, Peoples R China
基金
中国国家自然科学基金;
关键词
TPP 3D printing; vascularized organoids; artificialvessels; biomaterial engineering organoids; brainorganoids; CEREBRAL ORGANOIDS; MODEL; SPECIFICATION; INTERNEURONS; DIFFUSION; MIGRATION;
D O I
10.1021/acsnano.4c07844
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 mu m 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.
引用
收藏
页码:26201 / 26214
页数:14
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