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Recent advances in 3D models of the nervous system for neural regeneration research and drug development

Acta Biomaterialia 2025年

作者： Hui Zhu Cong Yao Zhengqi Xu Guojin Shang Jianhua Peng Huangfan Xie Tingyu Qian Zhennan Qiu Lidia Maeso Mao Mao Yucheng Liao Yong Jiang Dichen Li Gorka Orive Aldo R. Boccaccini State Key Laboratory for Manufacturing Systems Engineering Xi'an Jiaotong University Xi'an 710049 P. R. China National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices Xi'an Jiaotong University Xi'an 710049 P. R. China State Industry-Education Integration Center for Medical Innovations Xi'an Jiaotong University Xi'an 710049 P. R. China Department of Neurosurgery The Affiliated Hospital of Southwest Medical University Luzhou Sichuan 646000 China NanoBioCel Research Group School of Pharmacy University of the Basque Country (UPV/EHU) Vitoria-Gasteiz Spain Precision Pharmacy and Drug Development Center Department of Pharmacy Tangdu Hospital Air Force Medical University Xi' an Shaanxi China Bioaraba NanoBioCel Research Group Vitoria-Gasteiz Spain Biomedical Research Networking Centre in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) Vitoria-Gasteiz Spain University Institute for Regenerative Medicine and Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua) Vitoria 01007 Spain Institute of Biomaterials Department of Material Science and Engineering University of Erlangen-Nuremberg 91085 Erlangen Germany

The development of drugs for nervous diseases poses distinctive difficulties owing to the incomplete understanding of the physiology and complex pathogenesis of the multifaceted central (CNS) and peripheral (PNS) nervous systems. Conventional animal tests and in vitro two-dimensional (2D) cell cultures fail to reproduce the sophisticated structure of natural human tissues, hindering the new drug discovery process. The emerging three-dimensional (3D) neural tissue models, including organoids, organ-on-chips and 3D-printed neural scaffolds, can provide an improved reproduction of the critical features, structural complexity, biological functions, dynamic circulation micro-environment and cell-matrix/cell interactions of the nervous systems. This review examines state-of-the-art 3D models for neural physiology/pathology, emphasizing their drug development applications. Fundamental advantages of various in vitro 3D neural models for investigating the mechanisms of nerve regeneration and disorders in both the CNS and PNS are compared in terms of the different modeling techniques. In addition, the applications of 3D neural models in drug development are summarized covering a range of areas such as disease modeling for basic research, pharmacokinetic and pharmacodynamic testing for drug screening and drug safety evaluation. Furthermore, current challenges and future outlook of biomimetic models and the existing bottlenecks hindering their successful translation into clinical use are discussed. statement of significance This review highlights the groundbreaking potential of 3D neural models—organoids, organ-on-chips, and 3D-printed scaffolds—to revolutionize neurological research and drug development. Unlike conventional methods, these models replicate the intricate structure and function of human nervous systems, enabling precise study of diseases like Alzheimer’s, spinal injuries, and brain tumors. By synthesizing recent advancements, the review compares techniques, their

关键词： 3D neural tissue models CNS/PNS Drug development Nervous system-on-chips Neural organoids

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Phase-Separated Multienzyme Compartmentalization for Terpene Biosynthesis in a Prokaryote

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Angewandte Chemie 2022年第29期134卷

作者： Yue Wang Min Liu Qixin Wei Wanjie Wu Yanping He Jiayang Gao Renjie Zhou Liwen Jiang Jianan Qu Jiang Xia Department of Chemistry and Center for Cell & Developmental Biology The Chinese University of Hong Kong Shatin Hong Kong SAR China Departments of Electronic and Computer Engineering Center of Systems Biology and Human Health School of Science and Institute for Advanced Study Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong SAR China Department of Biomedical Engineering The Chinese University of Hong Kong Shatin Hong Kong SAR China Center for Cell & Developmental Biology School of Life Sciences State Key Laboratory of Agrobiotechnology The Chinese University of Hong Kong Shatin Hong Kong SAR China

Liquid–liquid phase separation (LLPS) forms biomolecular condensates or coacervates in cells. Metabolic enzymes can form phase-separated subcellular compartments that enrich enzymes, cofactors, and substrates. Herein, we report the construction of synthetic multienzyme condensates that catalyze the biosynthesis of a terpene, α-farnesene, in the prokaryote E. coli . RGGRGG derived from LAF-1 was used as the scaffold protein to form the condensates by LLPS. Multienzyme condensates were then formed by assembling two enzymes Idi and IspA through an RIAD/RIDD interaction. Multienzyme condensates constructed inside E. coli cells compartmentalized the cytosolic space into regions of high and low enzyme density and led to a significant enhancement of α-farnesene production. This work demonstrates LLPS-driven compartmentalization of the cytosolic space of prokaryotic cells, condensation of a biosynthetic pathway, and enhancement of the biosynthesis of α-farnesene.

关键词： α-Farnesene Multienzyme Catalysis Multienzyme Compartmentalization Phase Separation Terpene Biosynthesis

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Cryo-EM structure of human ATR-ATRIP complex

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细胞研究（英文版） 2018年第2期28卷 143-156页

作者： Qinhui Rao Mengjie Liu Yuan Tian Zihan Wu Yuhan Hao Lei Song Zhaoyu Qin Chen Ding Hong-Wei Wang Jiawei Wang Yanhui Xu Fudan University Shanghai Cancer Center Institute of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghai 200032China Key Laboratory of Molecular Medicine Ministry of EducationDepartment of Systems Biology for MedicineSchool of Basic Medical SciencesShanghai Medical College of Fudan UniversityShanghai 200032China State Key Laboratory of Genetic Engineering Collaborative Innovation Center of Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghai 200433China State Key Laboratory of Proteomics Beijing Proteome Research CenterBeijing Institute of Radiation Medicine National Center for Protein Sciences(The PHOENIX center Beijing)Beijing 102206China Fudan University Shanghai Cancer Center Institute of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghai 200032China Fudan University Shanghai Cancer Center Institute of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghai 200032China State Key Laboratory of Genetic Engineering Collaborative Innovation Center of Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghai 200433China Ministry of Education Key Laboratory of Protein Sciences Tsinghua-Peking Joint Center for Life SciencesBeijing Advanced Innovation Center for Structural BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Fudan University Shanghai Cancer Center Institute of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghai 200032China Key Laboratory of Molecular Medicine Ministry of EducationDepartment of Systems Biology for MedicineSchool of Basic Medical SciencesShanghai Medical College of Fudan UniversityShanghai 200032China State Key Laboratory of Genetic Engineering Collaborative Innovation Center of Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghai 200433China CAS Center for Excellence in Molecular Cell Science Chinese Academy of SciencesShanghai 200031China

ATR (ataxia telangiectasia-mutated and Rad3-related) protein kinase and ATRIP (ATR-interacting protein) form a complex and play a critical role in response to replication stress and DNA ***,we determined the cryo-electron microscopy (EM) structure of the human ATR-ATRIP complex at 4.7 (A) resolution and built an atomic model of the C-terminal catalytic core of ATR (residues 1 521-2 644) at 3.9(A) *** complex adopts a hollow "heart" shape,consisting of two ATR monomers in distinct *** EM map for ATRIP reveals 14 HEAT repeats in an extended "S" *** conformational flexibility of ATR allows ATRIP to properly lock the N-termini of the two ATR monomers to favor ATR-ATRIP complex formation and functional *** isolated "head-head"and "tail-tail" each adopts a pseudo 2-fold *** catalytic pockets face outward and substrate access is not restricted by inhibitory *** studies provide a structural basis for understanding the assembly of the ATR-ATRIP complex and a framework for characterizing ATR-mediated DNA repair pathways.

关键词： cryo-EM structure ATR ATRIP DNA damage response

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Interplay between the bacterial protein deacetylase CobB and the second messenger c-di-GMP

Interplay between the bacterial protein deacetylase CobB and...

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中国生物工程学会第十三届学术年会暨2019年全国生物技术大会

作者： Zhaowei Xu Hainan Zhang Xingrun Zhang Hewei Jiang Chengxi Liu Fanlin Wu Lili Qian Bingbing Hao Daniel M Czajkowsky Shujuan Guo Zhijing Xu Lijun Bi Shihua Wang Haitao Li Minjia Tan Wei Yan Lei Feng Jingli Hou Sheng-ce Tao Key Laboratory of Systems Biomedicine (Ministry of Education) Shanghai Center for Systems Biomedicine Shanghai Jiao Tong University MOE Key Laboratory of Protein Sciences Center for Structural Biology School of Life Sciences Tsinghua University Department of Basic Medical Sciences School of Medicine Tsinghua University The Chemical Proteomics Center and State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences School of Biomedical Engineering Shanghai Jiao Tong University College of Life Sciences Shanghai Normal University National Key Laboratory of Biomacromolecules Key Laboratory of Non-Coding RNA and Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics Chinese Academy of Sciences School of Stomatology and Medicine Foshan University School of Life Science Fujian Agriculture and Forestry University Instrumental Analysis Center Shanghai Jiao Tong University State Key Laboratory of Oncogenes and Related Genes

As a ubiquitous bacterial secondary messenger, c-di-GMP plays key regulatory roles in processes such as bacterial motility and transcription regulation. CobB is the Sir2 family protein deacetylase that controls energy metabolism, chemotaxis, and DNA supercoiling in many bacteria. Using an Escherichia coli proteome microarray, we found that c-di-GMP strongly binds to CobB. Further, protein deacetylation assays showed that c-di-GMP inhibits the activity of CobB and thereby modulates the biogenesis of acetyl-CoA. Interestingly, we also found that one of the key enzymes directly involved in c-di-GMP production, DgcZ, is a substrate of CobB. Deacetylation of DgcZ by CobB enhances its activity and thus the production of cdi-GMP. Our work establishes a novel negative feedback loop linking c-di-GMP biogenesis and CobB-mediated protein deacetylation.

关键词： c-di-GMP CobB diguanylate cyclase negative feedback loop protein acetylation

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Introduction to the Special Section: Convergence of Automation Technology, biomedical engineering, and Health Informatics Toward the Healthcare 4.0

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IEEE Reviews in biomedical engineering 2018年 11卷 249-259页

作者： Pang, Zhibo Yang, Geng Khedri, Ridha Zhang, Yuan-Ting ABB AB Corporate Research Vasteras72178 Sweden State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical Engineering Zhejiang University Hangzhou310027 China Department of Computing and Software Faculty of Engineering McMaster University HamiltonONL8S 4L8 Canada Department of Mechanical and Biomedical Engineering City University of Hong Kong Hong Kong Hong Kong

Industry 4.0 is spilling out from manufacturing to healthcare. In this article, we provide a brief history and key enabling technologies of Industry 4.0, and its revolution in healthcare - Healthcare 4.0 - and its reshaping of the landscape of the entire healthcare value chain. We discuss the shift in the system design paradigm from open, small, and single loop to closed, large, and multiple loops. We provide the example of a Caregiving Home, and discuss emerging research topics and challenges, including healthcare big data, automated medical production, healthcare robotics, and human-robot symbiosis. Relevant papers published in this special section are also presented. © 2008-2011 IEEE.

关键词： Industry 4.0

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Additive nanomanufacturing of lab-on-a-chip fluorescent peptide nanoparticle arrays for Alzheimer＇s disease diagnosis

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Bio-Design and Manufacturing 2018年第3期1卷 182-194页

作者： Leming Sun Zhen Fan Tao Yues Jun Yin Jianzhong FU Mingjun Zhang Department of Biomedical Engineering College ofEngineering Ohio State University Columbus OH 43210USA School of Life Sciences Northwestern PolytechnicalUniversity Xi'an 710072 Shaanxi China Department of Polymeric Materials School of MaterialScience and Engineering Tongji UniversityShanghai 201804 China Institute for Advanced Study TongjiUniversity Shanghai 200092 China School of Mechatronic Engineering and Automation Shanghai University Shanghai 200444 China The State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical Engineering ZhejiangUniversity Hangzhou 310028 China Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province School of Mechanical EngineeringZhejiang University Hangzhou 310028 China Dorothy M. Davis Heart & Lung Research Institute The OhioState University Wexner Medical Center Columbus OH43210 USA Interdisciplinary Biophysics Graduate Program Ohio StateUniversity Columbus OH 43210 USA

This paper proposes an additive nanomanufacturing approach to fabricate a personalized lab-on-a-chip fluorescent peptide nanoparticles （f-PNPs） array for simultaneous multi-biomarker detection that can be used in Alzheimer＇s disease （AD） diagnosis. We will discuss optimization techniques for the additive nanomanufacturing process in terms of reliability, yield and manufacturing efficiency. One contribution of this paper lies in utilization of additive nanomanufacturing techniques to fabricate a patient-specific customize-designed lab-on-a-chip device for personalized AD diagnosis, which remains a major challenge for biomedical engineering. Through the integrated bio-design and bio-manufacturing process, doctor＇s check- up and computer-aided customized design are integrated into the lab-on-a-chip array for patient-specific AD diagnosis. In addition, f-PNPs with targeting moieties for personalized AD biomarkers will be self-assembled onto the customized lab-on-a- chip through the additive nanomanufacturing process, which has not been done before. Another contribution of this research is the personalized lab-on-a-chip f-PNPs array for AD diagnosis utilizing limited human blood. Blood-based AD assessment has been described as ＂the holy grail＂ of early AD detection. This research created the computer-aided design, fabrication through additive nanomanufacturing, and validation of the f-PNPs array for AD diagnosis. This is a highly interdisciplinary research contributing to nanotechnology, biomaterials, and biomedical engineering for neurodegenerative disease. The conceptual work is preliminary with intent to introduce novel techniques to the application. Large-scale manufacturing based on the proposed framework requires extensive validation and optimization.

关键词： Nanomanufacturing Lab-on-a-chip Fluorescent peptide nanoparticle Alzheimer＇s disease Diagnosis

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Self-adaptation of chimera states

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Physical Review E 2019年第1期99卷 010201(R)-010201(R)页

作者： Nan Yao Zi-Gang Huang Hai-Peng Ren Celso Grebogi Ying-Cheng Lai Department of Applied Physics Xi'an University of Technology Xi'an 710048 China The Key Laboratory of Biomedical Information Engineering of Ministry of Education National Engineering Research Center of Health Care and Medical Devices The Key Laboratory of Neuro-informatics & Rehabilitation Engineering of Ministry of Civil Affairs and Institute of Health and Rehabilitation Science School of Life Science and Technology Xi'an Jiaotong University Xi'an 710049 China Shaanxi Key Laboratory of Complex System Control and Intelligent Information Processing Xi'an University of Technology Xi'an 710048 China Institute for Complex Systems and Mathematical Biology King's College University of Aberdeen Aberdeen AB24 3UE United Kingdom School of Electrical Computer and Energy Engineering Arizona State University Tempe Arizona 85287 USA Department of Physics Arizona State University Tempe Arizona 85287 USA

Chimera states in spatiotemporal dynamical systems have been investigated in physical, chemical, and biological systems, and have been shown to be robust against random perturbations. How do chimera states achieve their robustness? We uncover a self-adaptation behavior by which, upon a spatially localized perturbation, the coherent component of the chimera state spontaneously drifts to an optimal location as far away from the perturbation as possible, exposing only its incoherent component to the perturbation to minimize the disturbance. A systematic numerical analysis of the evolution of the spatiotemporal pattern of the chimera state towards the optimal stable state reveals an exponential relaxation process independent of the spatial location of the perturbation, implying that its effects can be modeled as restoring and damping forces in a mechanical system and enabling the articulation of a phenomenological model. Not only is the model able to reproduce the numerical results, it can also predict the trajectory of drifting. Our finding is striking as it reveals that, inherently, chimera states possess a kind of “intelligence” in achieving robustness through self-adaptation. The behavior can be exploited for the controlled generation of chimera states with their coherent component placed in any desired spatial region of the system.

关键词： Chimera states Collective dynamics Coupled oscillators Chaos & nonlinear dynamics

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Corrigendum to "Do theta oscillations explain the somatosensory change detection mechanism?" Biol. Psychol. 143 (2019) April 103-112

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Biological psychology 2021年 159卷 107995页

作者： Zhilin Zhang Guoxin Guo Jian Zhang Chunlin Li Qiang Huang Ritsu Go Hidenao Fukuyama Shintaro Funahashi Tianyi Yan Jinglong Wu Intelligent Robotics Institute School of Mechatronical Engineering Beijing Institute of Technology Beijing China Department of Psychiatry Graduate School of Medicine Kyoto University Kyoto Japan. School of Life Science Beijing Institute of Technology Beijing China. Intelligent Robotics Institute School of Mechatronical Engineering Beijing Institute of Technology Beijing China. School of Biomedical Engineering Capital Medical University Beijing China. International Joint Research Laboratory of Biomimetic Robots and Systems Ministry of Education Beijing China. Key Laboratory of Biomimetic Robots and Systems Ministry of Education Beijing China. Research and Educational Unit of Leaders for Integrated Medical System Center for the Promotion of Interdisciplinary Education and Research Kyoto University Kyoto Japan. Advanced Research Institute for Multidisciplinary Science Beijing Institute of Technology Beijing China. School of Life Science Beijing Institute of Technology Beijing China. Electronic address: yantianyi@***.

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Author Correction: Ionic shape-morphing microrobotic end-effectors for environmentally adaptive targeting, releasing, and sampling

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Nature communications 2021年第1期12卷 1598页

作者： Zhiqiang Zheng Huaping Wang Lixin Dong Qing Shi Jianing Li Tao Sun Qiang Huang Toshio Fukuda Intelligent Robotics Institute School of Mechatronical Engineering Beijing Institute of Technology 100081 Beijing China. Beijing Advanced Innovation Center for Intelligent Robots and Systems Beijing Institute of Technology 100081 Beijing China. wanghuaping@***. Department of Biomedical Engineering City University of Hong Kong 999077 Hong Kong China. Key Laboratory of Biomimetic Robots and Systems (Beijing Institute of Technology) Ministry of Education 100081 Beijing China. Beijing Advanced Innovation Center for Intelligent Robots and Systems Beijing Institute of Technology 100081 Beijing China. Beijing Advanced Innovation Center for Intelligent Robots and Systems Beijing Institute of Technology 100081 Beijing China. qhuang@***. Key Laboratory of Biomimetic Robots and Systems (Beijing Institute of Technology) Ministry of Education 100081 Beijing China. qhuang@***.

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Kirigami Metastructures: Liquid-Crystal-Elastomer-Actuated Reconfigurable Microscale Kirigami Metastructures (Adv. Mater. 25/2021)

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Advanced Materials 2021年第25期33卷

作者： Mingchao Zhang Hamed Shahsavan Yubing Guo Abdon Pena-Francesch Yingying Zhang Metin Sitti Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education Department of Chemistry Tsinghua University Beijing 100084 China Physical Intelligence Department Max Planck Institute for Intelligent Systems 70569 Stuttgart Germany Department of Chemical Engineering and Waterloo Institute for Nanotechnology University of Waterloo Waterloo ON N2L 3G1 Canada Department of Materials Science and Engineering Macromolecular Science and Engineering Robotics Institute University of Michigan Ann Arbor MI 48109 USA Institute for Biomedical Engineering ETH Zürich Zürich 8092 Switzerland School of Medicine and School of Engineering Koç University Istanbul 34450 Turkey

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