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AI-driven 3D bioprinting for regenerative medicine:From bench to bedside

Bioactive Materials 2025年第3期45卷 201-230页

作者： Zhenrui Zhang Xianhao Zhou Yongcong Fang Zhuo Xiong Ting Zhang Biomanufacturing Center Department of Mechanical EngineeringTsinghua UniversityBeijing100084PR China Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Beijing100084PR China “Biomanufacturing and Engineering Living Systems”Innovation International Talents Base(111 Base) Beijing100084PR China State Key Laboratory of Tribology in Advanced Equipment Tsinghua UniversityBeijing100084PR China

In recent decades,3D bioprinting has garnered significant research attention due to its ability to manipulate biomaterials and cells to create complex structures ***,due to technological and cost constraints,the clinical translation of 3D bioprinted products(BPPs)from bench to bedside has been hindered by challenges in terms of personalization of design and scaling up of ***,the emerging applications of artificial intelligence(AI)technologies have significantly improved the performance of 3D ***,the existing literature remains deficient in a methodological exploration of AI technologies’potential to over-come these challenges in advancing 3D bioprinting toward clinical *** paper aims to present a systematic methodology for AI-driven 3D bioprinting,structured within the theoretical framework of Quality by Design(QbD).This paper commences by introducing the QbD theory into 3D bioprinting,followed by sum-marizing the technology roadmap of AI integration in 3D bioprinting,including multi-scale and multi-modal sensing,data-driven design,and in-line process *** paper further describes specific AI applications in 3D bioprinting’s key elements,including bioink formulation,model structure,printing process,and function ***,the paper discusses current prospects and challenges associated with AI technologies to further advance the clinical translation of 3D bioprinting.

关键词： 3D bioprinting Artificial intelligence Machine learning Quality by design Regenerative medicine Clinical translation

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Creating a semi-opened micro-cavity ovary through sacrificial microspheres as an in vitro model for discovering the potential effect of ovarian toxic agents

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Bioactive Materials 2023年第8期26卷 216-230页

作者： Min Ye Yiran Shan Bingchuan Lu Hao Luo Binhan Li Yanmei Zhang Zixuan Wang Yuzhi Guo Liliang Ouyang Jin Gu Zhuo Xiong Ting Zhang Biomanufacturing Center Department of Mechanical EngineeringTsinghua UniversityBeijing100084China Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Beijing100084China Biomanufacturing and Engineering Living Systems Innovation International Talents Base(111 Base)Beijing100084China MOE Key Laboratory of Bioinformatics BNRIST Bioinformatics DivisionDepartment of AutomationTsinghua UniversityBeijing100084China

The bio-engineered ovary is an essential technology for treating female *** the development of relevant in vitro models could be a critical step in a drug ***,we develop a semi-opened culturing system(SOCS)strategy that maintains a 3D structure of follicles during the *** on the SOCS,we further developed micro-cavity ovary(MCO)with mouse follicles by the microsphere-templated technique,where sacrificial gelatin microspheres were mixed with photo-crosslinkable gelatin methacryloyl(GelMA)to engineer a micro-cavity niche for follicle *** semi-opened MCO could support the follicle growing to the antral stage,secreting hormones,and ovulating cumulus-oocyte complex out of the MCO without extra *** MCO-ovulated oocyte exhibits a highly similar transcriptome to the in vivo counterpart(correlation of 0.97)and can be ***,we found that a high ROS level could affect the cumulus expansion,which may result in anovulation *** damage could be rescued by melatonin,but the end of cumulus expansion was 3h earlier than anticipation,validating that MCO has the potential for investigating ovarian toxic agents in *** provide a novel approach for building an in vitro ovarian model to recapitulate ovarian functions and test chemical toxicity,suggesting it has the potential for clinical research in the future.

关键词： Bio-engineered ovary SOCS Semi-opened MCO Ovarian model Drug study

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Retrospective:Advances and Opportunities of 3D Bioprinting in China over Three Decades

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Additive Manufacturing Frontiers 2024年第4期3卷 29-43页

作者： Xianhao Zhou Yongcong Fang Ting Zhang Zhuo Xiong Biomanufacturing Center Department of Mechanical EngineeringTsinghua UniversityBeijing100084China Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Beijing100084China "Biomanufacturing and Engineering Living Systems"Innovation International Talents Base(111 Base) Beijing100084China

Three-dimensional(3D)bioprinting,which has been applied in tissue engineering and regenerative medicine,uses biomaterials,cells,and other essential components to manufacture organs and tissues with specific biological functions and complex *** the past 30 years,researchers have developed new 3D bioprinting technologies with improved manufacturing capabilities and expanded *** research teams contributed significantly to this *** this paper,we first reviewed the development history and major milestones in 3D bioprinting,categorizing them into two main strategies:"biomaterial-based indirect assembly"and"living cell-based direct assembly".This review further delved into the technical principles,recent advancements,advantages,disadvantages,and applications of each type of bioprinting ***,the challenges and future directions of 3D bioprinting were summarized to guide future research in China and foster advancements in this dynamic field.

关键词： 3D bioprinting Biofabrication Bioink Regenerative medicine Disease modeling

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Towards smart scanning probe lithography: a framework accelerating nano-fabrication process with in-situ characterization via machine learning

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Microsystems & Nanoengineering 2023年第5期9卷 281-294页

作者： Yijie Liu Xuexuan Li Ben Pei Lin Ge Zhuo Xiong Zhen Zhang State Key Laboratory of Tribology in Advanced Equipment Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China Beijing Key Laboratory of Precision/Ultra-precision Manufacturing Equipments and Control Tsinghua UniversityBeijing 100084China Biomanufacturing Center Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Beijing 100084China ‘Biomanufacturing and Engineering Living Systems’Innovation International Talents Base(111 Base) Beijing 100084China NT-MDT Spectrum Instruments China office Beijing 100053China

Scanning probe lithography(SPL)is a promising technology to fabricate high-resolution,customized and costeffective features at the ***,the quality of nano-fabrication,particularly the critical dimension,is significantly influenced by various SPL fabrication techniques and their corresponding process ***,the identification and measurement of nano-fabrication features are very time-consuming and *** tackle these challenges,we propose a novel framework for process parameter optimization and feature segmentation of SPL via machine learning(ML).Different from traditional SPL techniques that rely on manual labeling-based experimental methods,the proposed framework intelligently extracts reliable and global information for statistical analysis to finetune and optimize process *** on the proposed framework,we realized the processing of smaller critical dimensions through the optimization of process parameters,and performed direct-write nano-lithography on a large ***,data-driven feature extraction and analysis could potentially provide guidance for other characterization methods and fabrication quality optimization.

关键词： lithography process characterization

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Performance of Ti6Al4V fabricated by electron beam and laser hybrid preheating and selective melting strategy

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China Foundry 2021年第4期18卷 351-359页

作者： Mo-han Hao Lei Zhang Bin Zhou Hong-xin Li Ming-zhi Li Feng Lin Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China

Electron beam selective melting(EBM)and selective laser melting(SLM)are regarded as significant manufacturing processes for near-net-shaped Ti6Al4V ***,in the conventional EBM process,preheating is necessitated to avoid"smoke"caused by the charging of *** the conventional SLM process,laser as an energy source without the risk of"smoke"can be employed to melt metal powder at low ***,because of the low absorption rate of laser,the powder bed temperature cannot reach a high *** is difficult to obtain as-built TiAl4V with favorable comprehensive properties via conventional EBM or ***,two types of electron beam and laser hybrid preheating(EB-LHP)combined with selective melting strategies are *** laser to preheat powder allows EBM to be performed at a low powder bed temperature(EBM-LT),whereas using an electron beam to preheat powder allows SLM to be performed at a high powder bed temperature(SLM-HT).Ti6Al4V samples are fabricated using two different manufacturing strategies(i.e.,EBM-LT and SLM-HT)and two conventional processes,i.e.,EBM at a high powder bed temperature(EBM-HT)and SLM at a low powder bed temperature(SLM-LT).The temperature-dependent surface quality,microstructure,density,and mechanical properties of the as-built Ti6Al4V samples are characterized and *** show that EBM-LT Ti6Al4V exhibits a higher ultimate tensile strength(981±43 MPa)and a lower elongation(12.2%±2.3%)than EBM-HT Ti6Al4V owing to the presence ofα′*** SLM-HT Ti6Al4V possesses the highest ultimate tensile strength(1,059±62 MPa)and an elongation(14.8%±4.0%)comparable to that of the EBM-HT Ti6Al4V(16.6%±1.2%).

关键词： Ti6Al4V electron beam selective melting selective laser melting hybrid preheating

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Engineering vascularized organotypic tissues via module assembly

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International Journal of Extreme Manufacturing 2024年第1期6卷 155-175页

作者： Zhenzhen Zhou Changru Liu Yuting Guo Yuan Pang Wei Sun Biomanufacturing Center Department of Mechanical EngineeringTsinghua UniversityHaidian DistrictBeijing 100084People’s Republic of China Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Beijing 100084People’s Republic of China Key Laboratory for Advanced Materials Processing Technology Ministry of EducationBeijing 100084People’s Republic of China Department of Mechanical Engineering Drexel UniversityPhiladelphiaPA 19104United States of America

Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.

关键词： vascularized organotypic tissue module assembly regenerative medicine tissue engineering

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Additive Manufacturing of Nickel-Based Superalloy Single Crystals with IN-738 Alloy

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Acta Metallurgica Sinica(English Letters) 2022年第3期35卷 369-374页

作者： Yang Li Ye-Feng Yu Zhi-Bin Wang Xiao-Yu Liang Wen-Bin Kan Feng Lin Department of Mechanical Engineering Tsinghua UniversityBeijing 100084China Key Laboratory for Advanced Materials Processing Technology Ministry of Education of ChinaBeijing 100084China Bio-Manufacturing and Rapid Forming Technology Key Laboratory of Beijing Beijing 100084China

The production of non-weldable nickel-based superalloys,especially single-crystal superalloys,is important for additive ***-crystal specimens of non-weldable nickel-based superalloys were produced by electron beam selective melting using an IN-738 *** this study,single-crystal nickel-based superalloy specimens of diff erent sizes were prepared by a multiple preheating process and tight control of the melting parameters without the need for a grain selector or single-crystal seed for the first *** backscattered diff raction measurements were performed to confi rm the presence of a single *** transition boundaries between the polycrystalline and single-crystal regions at the edges and bottom of the samples were characterized to analyze the formation of single crystals.

关键词： Non-weldable superalloys Electron beam selective melting Single crystal Grain selection

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Three-dimensional-engineered bioprinted in vitro human neural stem cell self-assembling culture model constructs of Alzheimer’s disease

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Bioactive Materials 2022年第5期7卷 192-205页

作者： Yi Zhang Haiyan Chen Xiaoyan Long Tao Xu Tsinghua Shenzhen International Graduate School Tsinghua UniversityShenzhen518055China East China Institute of Digital Medical Engineering Shangrao334000China Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Department of Mechanical EngineeringTsinghua UniversityBeijing100084People’s Republic of China

The pathogenic cascade of Alzheimer’s disease(AD)characterized by amyloid-β protein accumulation is still poorly understood,partially owing to the limitations of relevant models without in vivo neural tissue microenvironment to recapitulate cell-cell *** better mimic neural tissue microenvironment,three-dimensional(3D)core-shell AD model constructs containing human neural progenitor cells(NSCs)with 2% matrigel as core bioink and 2% alginate as shell bioink have been bioprinted by a co-axial bioprinter,with a suitable shell thickness for nutrient exchange and barrier-free cell interaction *** constructs exhibit cell self-clustering and-assembling properties and engineered reproducibility with long-term cell viability and self-renewal,and a higher differentiation level compared to 2D and 3D MIX *** different effects of 3D bioprinted,2D,and MIX microenvironments on the growth of NSCs are mainly related to biosynthesis of amino acids and glyoxylate and dicarboxylate metabolism on day 2 and ribosome,biosynthesis of amino acids and proteasome on day ***,the model constructs demonstrated Aβ aggregation and higher expression of Aβ and tau isoform genes compared to 2D and MIX *** model constructs will provide a promising strategy to facilitate the development of a 3D in vitro AD model for neurodegeneration research.

关键词： 3D bioprinting Co-axial In vitro AD model Self-assembling

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Coaxial bioprinted microfibers with mesenchymal stem cells for glioma microenvironment simulation

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Bio-Design and Manufacturing 2022年第2期5卷 348-357页

作者： Zhizhong Jin Xinda Li Boxun Liu Xinru Yan Shuai Han Tao Xu Anhua Wu Department of Neurosurgery The First Hospital of China Medical UniversityShenyang 110001China Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China Department of Precision Medicine and Healthcare Tsinghua-Berkeley Shenzhen InstituteShenzhen 518055China East China Institute of Digital Medical Engineering Shangrao 334000China

Due to their special anatomical and physiological features,central nervous system diseases still presented challenges,despite the fact that some advances have been made in early diagnosis and precision *** of the complexities in treating tumors is the tumor microenvironment,which includes mesenchymal stem cells(MSCs)that exhibit tumor tropism and can be used for cell ***,whether MSCs promote or suppress gliomas is still unclear,especially in glioma *** this study,a coaxial microfiber was designed to mimic the tumor microenvironment and to reveal the effect of MSCs on glioma *** fiber shell was composed of MSCs and alginate,and the core was filled with U87 MG(glioblastoma)cells and gelatin *** Shell-MSC/Core-U87 MG microenvironment improved the proliferation,survival,invasion,metastasis,and drug resistance of glioma cells,while simultaneously maintaining the stemness of glioma *** summary,coaxial extrusion bioprinted Shell-MSC/Core-U87 MG microfiber is an ideal platform for tumor and stromal cell coculture to observe tumor biological behavior in vitro.

关键词： Coaxial bioprinting GBM microenvironment MSC Coculture

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Electron Beam Powder Bed Fusion Additive Manufacturing:A Comprehensive Review and its Development in China

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Additive Manufacturing Frontiers 2024年第4期3卷 75-101页

作者： Mohan Jiao Hongyu Long Buwei Xiao Xiaoyu Liang Feng Lin State Key Laboratory of Clean and Efficient Turbomachinery Power Equipment Department of Mechanical EngineeringTsinghua UniversityBeijing100084China Key Laboratory for Advanced Materials Processing Technology Ministry of EducationBeijing100084China Bio-Manufacturing and Rapid Forming Technology Key Laboratory of Beijing Beijing100084China State Key Laboratory of Nonferrous Metals and Specialty Materials Processing Guangxi UniversityNanning530004China

Additive manufacturing(AM),recognized as a pivotal innovation,has revolutionized the manufacturing industry since its *** a robust background of over three decades in AM,China has accomplished significant milestones,emerging as a key global player in the deployment and export of related machinery and ***’s prominence within the realm of powder bed fusion technology is underscored by its substantial market *** beam powder bed fusion(EB-PBF),known for its low residual stress and high forming efficiency,has gained considerable international *** Tsinghua University initiated the first research on EB-PBF in 2004,China has steadily advanced in this area,leading to the commercialization of EB-PBF devices and the development of a diverse product *** comprehensive review highlights the research progress in EB-PBF,focusing on its development in China,explores novel technologies,and offers insights into future advancements.

关键词： Additive manufacturing Electron beam powder bed fusion Electron beam melting Materials processing Simulation

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