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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

Development of a Tribofidelic Human Heel Surrogate for Barefoot Slip Testing

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Journal of Bionic engineering 2022年第2期19卷 429-439页

作者： Subhodip Chatterjee Arnab Chanda Centre for biomedical engineering Indian Institute of Technology DelhiNew Delhi 110016India Department of biomedical engineering All India Institute of Medical ScienceNew Delhi 110029India

Barefoot slips contribute to over 37% of recurrent fall-related injuries across all age groups.To study slip risk across a wide range of flooring conditions,slip meters with barefoot surrogates(i.e.,sensors,as per ASTM standard nomenclature)such as animal skins and rubbers have been used to date,which exhibit biomechanical and frictional properties widely different from the barefoot human skin.Development of a surrogate which can accurately simulate the human heel skin properties would be immensely beneficial for realistic assessment of barefoot slipping risk.A novel surrogate was developed using 3D scanning and printing,and biomimetics,which precisely simulates the biomechanical and frictional properties of the barefoot human heel skin.Mechanical slip testing was conducted with this surrogate on three common bathroom floorings and with six different contaminants.Coefficient of Friction(COF)results similar to human slipping experiments,high repeatability and reproducibility across wet and oily flooring conditions,were confirmed through experiments with the developed heel skin surrogate.The heel skin surrogate would be an indispensable model for accurate estimation of barefoot risk against slips and falls in bathrooms,bathtubs,and swimming pools.

关键词： Barefoot Surrogate Slip Fall Bathroom Bathtub

Biodegradable magnesium materials regulate ROS-RNS balance in pro-inflammatory macrophage environment

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Bioactive Materials 2023年第5期23卷 261-273页

作者： Maria P.Kwesiga Amani A.Gillette Fatemeh Razaviamri Margaret E.Plank Alexia L.Canull Zachary Alesch Weilue He Bruce P.Lee Roger J.Guillory II Department of biomedical engineering Michigan Technological UniversityHoughtonMIUSA Morgridge institute for Research MadisonWIUSA Department of biomedical engineering University of Wisconsin-MadisonMadisonWIUSA

The relationship between reactive oxygen and nitrogen species(ROS-RNS)secretion and the concomitant biocorrosion of degradable magnesium(Mg)materials is poorly understood.We found that Mg foils implanted short term in vivo(24 h)displayed large amounts of proinflammatory F4/80+/iNOS+macrophages at the interface.We sought to investigate the interplay between biodegrading Mg materials(98.6%Mg,AZ31&AZ61)and macrophages(RAW 264.7)stimulated with lipopolysaccharide(RAW 264.7^(LPS))to induce ROS-RNS secretion.To test how these proinflammatory ROS-RNS secreting cells interact with Mg corrosion in vitro,Mg and AZ61 discs were suspended approximately 2 mm above a monolayer of RAW 264.7 cells,either with or without ^(LPS).The surfaces of both materials showed acute(24 h)changes when incubated in the proinflammatory RAW 264.7^(LPS) environment.Mg discs incubated with RAW 264.7^(LPS) macrophages showed greater corrosion pitting,while AZ61 showed morphological and elemental bulk product changes via scanning electron microscopy-energy dispersive X-ray spectroscopy(SEM-EDX).X-ray photoelectron spectroscopy(XPS)analysis showed a reduction in the Ca/P ratio of the surface products for AZ61 disc incubated with RAW 264.7^(LPS),but not the Mg discs.Moreover,RAW 264.7^(LPS) macrophages were found to be more viable in the acute biodegradative environment generated by Mg materials,as demonstrated by calcein-AM and cleaved(active)caspase-3 staining(CC3).^(LPS) stimulation caused an increase in ROS-RNS,and a decrease in antioxidant peroxidase activity.Mg and AZ61 were found to change this ROS-RNS balance,independently of physiological antioxidant mechanisms.The findings highlight the complexity of the cellular driven acute inflammatory responses to different biodegradable Mg,and how it can potentially affect performance of these materials.

关键词： Biocorrosion Macrophage activation Nitroso-redox balance Mg

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 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

Octahedral silver oxide nanoparticles enabling remarkable SERS activity for detecting circulating tumor cells

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Science China(Life Sciences) 2022年第3期65卷 561-571页

作者： Meng He Jie Lin Ozioma Udochukwu Akakuru Xiawei Xu Yanying Li Yi Cao Yanping Xu Aiguo Wu Cixi Institute of Biomedical Engineering International Cooperation Base of Biomedical Materials Technology and ApplicationCAS Key Laboratory of Magnetic Materials and Devices&Zhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China Nano Science and Technology institute University of Science and Technology of ChinaSuzhou 215123China

The detection of circulating tumor cells(CTCs)is a crucial tool for early cancer diagnosis,prognosis,and postoperative evaluation.However,detection sensitivity remains a major challenge because CTCs are extremely rare in peripheral blood.To effectively detect CTCs,octahedral Ag_(2)O nanoparticles(NPs)with high dispersibility,good biocompatibility,remarkable surface-enhanced Raman scattering(SERS)enhancement,and obvious enhancement selectivity are designed as an SERS platform.Ag_(2)O NPs with many oxygen vacancy defects are successfully synthesized,which exhibit an ultra-high SERS enhancement factor(1.98×10^(6))for 4-mercaptopyridine molecules.The remarkable SERS activity of octahedral Ag_(2)O NPs is derived from the synergistic effect of the surface defect-promoted photo-induced charge transfer(PICT)process and strong vibration coupling resonance in the Ag_(2)O-molecule SERS complex,greatly amplifying the molecular Raman scattering crosssection.The promoted PICT process is confirmed using ultraviolet-visible(UV-Vis)absorption spectroscopy,demonstrating that obvious PICT resonance occurs in Ag_(2)O SERS system under visible light.An additional growth step of SERS bioprobe is proposed by modifying the Raman signal molecules and functional biological molecules on Ag_(2)O NPs for CTC detection.The Ag_(2)O-based SERS bioprobe exhibits excellent detection specificity for different cancer cells in rabbit blood.Importantly,the high-sensitivity Ag_(2)O-based SERS bioprobe satisfies the requirement for rare CTC detection in the peripheral blood of cancer patients,and the detection limit can reach 1 cell per m L.To our knowledge,this study is the first time that a semiconductor SERS substrate has been successfully utilized in CTC detection.This work provides new insights into CTC detection and the development of novel semiconductor-based SERS platforms for cancer diagnosis.

关键词： SERS CTCs octahedral Ag_(2)O NPs PICT cancer diagnosis

Tunable catalytic release of nitric oxide via copper‐loaded coatings on titanium nanotubes for regulating biological performance

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Biosurface and Biotribology 2023年第2期9卷 45-57页

作者： Zhiyong Li Lu Zhang Lei Zhou Xin Li Yuancong Zhao Jin Wang Institute of Biomedical Engineering College of MedicineSouthwest Jiaotong UniversityChengduSichuanChina

Severe lesions in vessels need to be treated with implantable interventional devices such as vascular stents,which should be anti‐coagulantion,anti‐proliferation and promoting endothelialisation.Nitric oxide(NO),as a physiological gas signalling molecule,play an important role in revascularisation.Catalysing the release of NO from endogenous do-nors has already been widely favoured to treatment strategy for lesioned vessels.In this work,a series of copper‐loaded coatings(titanium nanotube(TNT)/PDA‐Cu)was fabricated by TNTs combined with polydopamine and ions,which achieve controlled in situ catalytic release of NO.This strategy could effectively immobilised copper ions on TNTs,and promoted the proliferation of endothelial cells and inhibited growth of smooth muscle cells(SMCs)via the performance of NO,as well as restrain the platelet adhesion.With the multiple function,TNT/PDA‐Cu provides a promise approach for promoting endothelialisation,anti‐coagulation and inhibition of SMC proliferation via copper‐loaded coatings on TNTs.

关键词： copper ions in‐situ release nitric oxide titanium nanotubes

Multifocal structured illumination optoacoustic microscopy

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Light(Science & Applications) 2020年第1期9卷 568-576页

作者： Zhenyue Chen Ali Ozbek Johannes Rebling Quanyu Zhou Xose Luis Dean-Ben Daniel Razansky institute for biomedical engineering and institute of Pharmacology and Toxicology University of Zurich and ETH ZurichZurichSwitzerland

Optoacoustic(OA)imaging has the capacity to effectively bridge the gap between macroscopic and microscopic realms in biological imaging.High-resolution OA microscopy has so far been performed via point-by-point scanning with a focused laser beam,thus greatly restricting the achievable imaging speed and/or field of view.Herein we introduce multifocal structured illumination OA microscopy(MSIOAM)that attains real-time 3D imaging speeds.For this purpose,the excitation laser beam is shaped to a grid of focused spots at the tissue surface by means of a beamsplitting diffraction grating and a condenser and is then scanned with an acousto-optic deflector operating at kHz rates.In both phantom and in vivo mouse experiments,a 10mm wide volumetric field of view was imaged with 15 Hz frame rate at 28μm spatial resolution.The proposed method is expected to greatly aid in biological investigations of dynamic functional,kinetic,and metabolic processes across multiple scales.

关键词： illumination beam excitation

Investigation on baicalin‐loaded chitosan film crosslinked by graphene oxide and its biocompatibility

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Biosurface and Biotribology 2023年第2期9卷 35-44页

作者： Yu Zhu Lu Zhang Lei Zhou Xin Li Yuancong Zhao Jin Wang Institute of Biomedical Engineering College of MedicineSouthwest Jiaotong UniversityChengduSichuanChina

Chitosan has good biocompatibility,in vivo biodegradability and certain physiological activity,which can be used as a drug carrier to stabilise and protect drug components,causing the promotion of drug absorption and controlling drug release.Using graphene oxide(GO)as a cross‐linking agent,the functional groups in its lamellar structure can interact effectively with the functional groups in chitosan molecules,leading to enhanced mechanical properties and optimize the controlled drug‐release behaviour.GO/chitosan composite films were prepared by the solution mixing method with various GO content and exhibit many hydrogen bonds between the GO and chitosan.There were no obvi-ously agglomerated GO particles in the surface of composite films,and the lamellar structure can be observed in the cross section of the composite films.Differential thermal analysis(DTA)indicated that the addition of GO increased the stability of the chitosan film.The baicalin‐loaded GO/Chitosan also exhibited pH dependent release behaviour,with an increasing release amount and rate at lower pH medium.In addition,the result of biological evaluations showed that the GO/Chitosan films had good cytocompatibility in vitro and histocompatibility at appropriate GO concentrations.This investigation offered a new pH‐dependent drug carrier potentially applied for tumour and atherosclerosis treatment.

关键词： biomaterials coatings graphene oxide

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