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Journal of Zhejiang University-Science A(Applied Physics & engineering) 2024年第1期25卷 79-96页

作者： Haoyu SUN Haiyang MA Li WANG Yang LIU Tian HOU Wenjie TANG Qing YU Meiwen AN Meiling WEN institute of biomedical engineering College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China

Three-dimensional(3D)hydrogel models play a crucial role in tissue engineering for promoting tissue regeneration.A biomimetic microchannel network system in the 3D hydrogel model is necessary for optimal cellular function.This report describes the preparation of a biomimetic hydrogel scaffold with an internal microchannel network,using electrospinning techniques and the sacrificial template method for 3D cell culture.Microchannels and cavities were created within the gelatin methacryloyl(GelMA)hydrogel by sacrificing polyvinyl alcohol(PVA)electrospun fibers(>10µm),resulting in the creation of microvessel-like channels.Mechanical characterizations,swelling properties,and biodegradation analysis were conducted to investigate the feasibility of a biomimetic microchannel network hydrogel scaffold for 3D cell culture applications.Compared to pure GelMA hydrogel,the hydrogel with microchannels promoted cell proliferation,adhesion,and endothelial tube formation.Moreover,the results confirmed that the biomimetic microchannel network scaffold had a major impact on the distribution and arrangement of human umbilical vein endothelial cells(HUVECs)and can enable the formation of artificial microvasculature by the culture of HUVECs and cell media perfusion.

关键词： Biomimetic scaffold Photocrosslinking Microchannel network Tissue engineering Artificial microvascular

Micro/nanosystems for controllable drug delivery to the brain

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The Innovation 2024年第1期5卷 139-157页

作者： Mingzhen Tian Zhichao Ma Guang-Zhong Yang institute of Medical Robotics School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200240China

Drug delivery to the brain is crucial in the treatment for central nervous system disorders.While significant progress has been made in recent years,there are still major challenges in achieving controllable drug delivery to the brain.Unmet clinical needs arise from various factors,including controlled drug transport,handling large drug doses,methods for crossing biological barriers,the use of imaging guidance,and effective models for analyzing drug delivery.Recent advances in micro/nanosystems have shown promise in addressing some of these challenges.These include the utilization of microfluidic platforms to test and validate the drug delivery process in a controlled and biomimetic setting,the development of novel micro/nanocarriers for large drug loads across the blood-brain barrier,and the implementation of micro-intervention systems for delivering drugs through intraparenchymal or peripheral routes.In this article,we present a review of the latest developments in micro/nanosystems for controllable drug delivery to the brain.We also delve into the relevant diseases,biological barriers,and conventional methods.In addition,we discuss future prospects and the development of emerging robotic micro/nanosystems equipped with directed transportation,real-time image guidance,and closed-loop control.

关键词： equipped doses barriers

A highly sensitive LITES sensor based on a multi-pass cell with dense spot pattern and a novel quartz tuning fork with low frequency

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Opto-Electronic Advances 2024年第3期7卷 26-34页

作者： Yahui Liu Shunda Qiao Chao Fang Ying He Haiyue Sun Jian Liu Yufei Ma National Key Laboratory of Science and Technology on Tunable Laser Harbin Institute of TechnologyHarbin 150000China Zhengzhou Research institute Harbin Institute of TechnologyZhengzhou 450000China Advanced Microscopy and instrumentation Research Center School of Instrumentation Science and EngineeringHarbin Institute of TechnologyHarbin 150080China.

A highly sensitive light-induced thermoelectric spectroscopy(LITES)sensor based on a multi-pass cell(MPC)with dense spot pattern and a novel quartz tuning fork(QTF)with low resonance frequency is reported in this manuscript.An erbi-um-doped fiber amplifier(EDFA)was employed to amplify the output optical power so that the signal level was further enhanced.The optical path length(OPL)and the ratio of optical path length to volume(RLV)of the MPC is 37.7 m and 13.8 cm^(-2),respectively.A commercial QTF and a self-designed trapezoidal-tip QTF with low frequency of 9461.83 Hz were used as the detectors of the sensor,respectively.The target gas selected to test the performance of the system was acetylene(C2H2).When the optical power was constant at 1000 mW,the minimum detection limit(MDL)of the C2H2-LITES sensor can be achieved 48.3 ppb when using the commercial QTF and 24.6 ppb when using the trapezoid-al-tip QTF.An improvement of the detection performance by a factor of 1.96 was achieved after replacing the commer-cial QTF with the trapezoidal-tip QTF.

关键词： light-induced thermoelectric spectroscopy quartz tuning fork multi-pass cell gas sensing

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Liquid metal biomaterials: translational medicines,challenges and perspectives

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National Science Review 2024年第2期11卷 264-284页

作者： Hanchi Xu Jincheng Lu Yikuang Xi Xuelin Wang Jing Liu Department of biomedical engineering School of Medicine Tsinghua University Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Shanghai World Foreign Language Academy Beijing Advanced Innovation Center for biomedical engineering School of Engineering MedicineBeihang University Beijing Key Lab of Cryo-biomedical engineering and Key Lab of Cryogenics Technical Institute of Physics and Chemistry Chinese Academy of Sciences

Until now, significant healthcare challenges and growing urgent clinical requirements remain incompletely addressed by presently available biomedical materials. This is due to their inadequate mechanical compatibility, suboptimal physical and chemical properties, susceptibility to immune rejection, and concerns about long-term biological safety. As an alternative, liquid metal(LM) opens up a promising class of biomaterials with unique advantages like biocompatibility, flexibility, excellent electrical conductivity,and ease of functionalization. However, despite the unique advantages and successful explorations of LM in biomedical fields, widespread clinical translations and applications of LM-based medical products remain limited. This article summarizes the current status and future prospects of LM biomaterials, interprets their applications in healthcare, medical imaging, bone repair, nerve interface, and tumor therapy, etc.Opportunities to translate LM materials into medicine and obstacles encountered in practices are discussed.Following that, we outline a blueprint for LM clinics, emphasizing their potential in making new-generation artificial organs. Last, the core challenges of LM biomaterials in clinical translation, including bio-safety,material stability, and ethical concerns are also discussed. Overall, the current progress, translational medicine bottlenecks, and perspectives of LM biomaterials signify their immense potential to drive future medical breakthroughs and thus open up novel avenues for upcoming clinical practices.

关键词： liquid metal biomaterials translational medicine clinical device healthcare therapeutics

class activation maps;laser-induced damage;semantic segmentation;weakly supervised learning

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High Power Laser Science and engineering 2024年第1期12卷 30-41页

作者： Yueyue Han Yingyan Huang Hangcheng Dong Fengdong Chen Fa Zeng Zhitao Peng Qihua Zhu Guodong Liu School of instrumentation Science and engineering Harbin Institute of TechnologyHarbinChina Research Center of Laser Fusion China Academy of Engineering PhysicsMianyangChina

Segmenting dark-field images of laser-induced damage on large-aperture optics in high-power laser facilities is challenged by complicated damage morphology, uneven illumination and stray light interference. Fully supervised semantic segmentation algorithms have achieved state-of-the-art performance but rely on a large number of pixel-level labels, which are time-consuming and labor-consuming to produce. LayerCAM, an advanced weakly supervised semantic segmentation algorithm, can generate pixel-accurate results using only image-level labels, but its scattered and partially underactivated class activation regions degrade segmentation performance. In this paper, we propose a weakly supervised semantic segmentation method, continuous gradient class activation mapping(CAM) and its nonlinear multiscale fusion(continuous gradient fusion CAM). The method redesigns backpropagating gradients and nonlinearly activates multiscale fused heatmaps to generate more fine-grained class activation maps with an appropriate activation degree for different damage site sizes. Experiments on our dataset show that the proposed method can achieve segmentation performance comparable to that of fully supervised algorithms.

关键词： class activation maps laser-induced damage semantic segmentation weakly supervised learning

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Recent advances in small-scale hydrogel-based robots for adaptive biomedical applications

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Nano Research 2024年第2期17卷 649-662页

作者： Mingzhe Nie Qilong Zhao Xuemin Du institute of biomedical&Health engineering Shenzhen Institute of Advanced Technology(SIAT)Chinese Academy of Sciences(CAS)Shenzhen 518055China

Small-scale robots,ranging in size from micrometers to centimeters,have gained significant attention in the biomedical field.However,conventional small-scale robots made of rigid materials encounter challenges in adapting themselves to the soft tissues and complicated environments of human body.Compared to the rigid counterpart,small-scale hydrogel-based robots hold great promises due to their tissue-like low modulus,outstanding biocompatibility and accessible stimuli-responsive capabilities.These attributes offer small-scale hydrogel-based robots with multimodal locomotion and reinforced functions,further enhancing the adaptability in manipulation and tasks execution for various biomedical applications.In this review,we present recent advances in small-scale hydrogel-based robots.We first summarize the design principles of small-scale hydrogel-based robots including materials,fabrication techniques and manipulation strategies,then highlighting their upgraded functions and adaptive biomedical applications.Finally,we discuss existing challenges and future perspectives for small-scale hydrogel-based robots.

关键词： small-scale robot hydrogel locomotion multi-function adaptability

A muon high-resolution pseudorange measurement method: Application to muon navigation in confined spaces

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Chinese Journal of Aeronautics 2024年第4期37卷 391-404页

作者： Haoyang LI Chunxi ZHANG Xingming FAN Longjie TIAN Tianqi LI Yang PANG Yanqiang YANG institute of Optics and Electronics School of Instrumentation Science and Optoelectronics EngineeringBeihang UniversityBeijing 100191China institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China

Confined spaces such as polar regions, deep earth and deep ocean are crucial navigation scenarios where traditional navigation techniques have difficulty in obtaining external signals for positioning. The cosmic ray muons, which carry the spatial and energetic information, are easy to penetrate these confined spaces. Therefore, the unique muon characteristic provides a new perspective to estimate detector position, which can be considered using in confined spaces navigation.In this paper, a well-developed theory of muon navigation is established by combining a muon pseudorange measurement method. Moreover, an Equivalent Velocity Calculation Model(EVCM)and a Muon Sequence Matching Technology(MSMT) are proposed. The first model corrects flight pseudorange error caused by the relativistic energy loss and the second technology compensates the random error in pseudorange measurement. Further, a series of simulations are performed to analyze the muon events number which can be received by detector in different scenarios with the variations of zenith angle, detector area, varied detector plates gap, and muon flight distance.Meanwhile, the simulation results demonstrate that the muon navigation update rate every 10 minutes can reach 5.989 in confined spaces at 100 m, and further pseudorange error analysis indicates that the meter-level positioning accuracy can be acquired. Finally, we construct a muon coincidence measurement scheme and verify that the laws of the muon positioning system for high-energy muons are consistent with the simulation results.

关键词： Muon navigation Cosmic ray muons Muon detection technology Muon transmission technology Pseudorange measurement

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Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 69-85页

作者： Noehyun Myung Hyun-Wook Kang Department of biomedical engineering Ulsan National Institute of Science and Technology(UNIST)Ulju-gun 44919South Korea

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

关键词： Dose-dense chemotherapy Triple-negative breast cancer 3D printing Pulsatile release Local drug delivery systems

A comprehensive review on surface modifications of black phosphorus using biological macromolecules

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Frontiers of Materials Science 2024年第2期18卷 37-59页

作者： Chaiqiong Guo Xuhong He Xuanyu Liu Yuhui Wang Yan Wei Ziwei Liang Di Huang Department of biomedical engineering Research Center for Nano-biomaterials&Regenerative MedicineCollege of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan 030024China Shanxi-Zheda institute of Advanced Materials and Chemical engineering Taiyuan 030032China

Black phosphorus(BP),a novel two dimensional material,exhibits remarkable photoelectric characteristics,ultrahigh photothermal conversion efficiency,substantial specific surface area,high carrier mobility,and tunable band gap properties.These attributes have positioned it as a promising candidate in domains such as energy,medicine,and the environment.Nonetheless,its vulnerability to light,oxygen,and water can lead to rapid degradation and loss of crystallinity,thereby limiting its synthesis,preservation,and application.Moreover,BP has demonstrated cytotoxic tendencies,substantially constraining its viability in the realm of biomedicine.Consequently,the imperative for surface modification arises to bolster its stability and biocompatibility,while concurrently expanding its utility spectrum.Biological macromolecules,integral components of living organisms,proffer innate advantages over chemical agents and polymers for the purpose of the BP modifications.This review comprehensively surveys the advancements in utilizing biological macromolecules for the modifications of BP.In doing so,it aims to pave the way for enhanced stability,biocompatibility,and diversified applications of this material.

关键词： blackphosphorus tumor therapy biocompatibility surface modification biomacromolecule

A comprehensive review of 3D cancer models for drug screening and translational research

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Cancer Innovation 2024年第1期3卷 61-78页

作者： Karthikey Sharma Sreenath Dey Rounik Karmakar Aravind Kumar Rengan Department of biomedical engineering Indian Institute of Technology(IIT)HyderabadIndia

The 3D cancer models fill the discovery gap of 2D cancer models and play an important role in cancer research.In addition to cancer cells,a range of other factors include the stroma,density and composition of extracellular matrix,cancer-associated immune cells(e.g.,cancer-associated fibroblasts cancer cell-stroma interactions and subsequent interactions,and a number of other factors(e.g.,tumor vasculature and tumor-like microenvironment in vivo)has been widely ignored in the 2D concept of culture.Despite this knowledge,the continued use of monolayer cell culture methods has led to the failure of a series of clinical trials.This review discusses the immense importance of tumor microenvironment(TME)recapitulation in cancer research,prioritizing the individual roles of TME elements in cancer histopathology.The TME provided by the 3D model fulfills the requirements of in vivo spatiotemporal arrangement,components,and is helpful in analyzing various different aspects of drug sensitivity in preclinical and clinical trials,some of which are discussed here.Furthermore,it discusses models for the co-assembly of different TME elements in vitro and focuses on their synergistic function and responsiveness as tumors.Furthermore,this review broadly describes of a handful of recently developed 3D models whose main focus is limited to drug development and their screening and/or the impact of this approach in preclinical and translational research.

关键词： 3D models cancer drug development translational research tumor microenvironment elements