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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 *** 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 *** 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 *** characterizations,swelling properties,and biodegradation analysis were conducted to investigate the feasibility of a biomimetic microchannel network hydrogel scaffold for 3D cell culture *** to pure GelMA hydrogel,the hydrogel with microchannels promoted cell proliferation,adhesion,and endothelial tube ***,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

Unveiling protein corona composition:predicting with resampling embedding and machine learning

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Regenerative Biomaterials 2024年第1期3卷 27-33页

作者： Rong Liao Yan Zhuang Xiangfeng Li Ke Chen Xingming Wang Cong Feng Guangfu Yin Xiangdong Zhu Jiangli Lin Xingdong Zhang College of biomedical engineering National Engineering Research Centre for BiomaterialsSichuan UniversityChengdu610065China

Biomaterials with surface nanostructures effectively enhance protein secretion and stimulate tissue *** nanoparticles(NPs)enter the living system,they quickly interact with proteins in the body fluid,forming the protein corona(PC).The accurate prediction of the PC composition is critical for analyzing the osteoinductivity of biomaterials and guiding the reverse design of ***,achieving accurate predictions remains a significant *** several machine learning(ML)models like Random Forest(RF)have been used for PC prediction,they often fail to consider the extreme values in the abundance region of PC absorption and struggle to improve accuracy due to the imbalanced data *** this study,resampling embedding was introduced to resolve the issue of imbalanced distribution in PC *** ML models were evaluated,and RF model was finally used for prediction,and good correlation coefficient(R^(2))and root-mean-square deviation(RMSE)values were *** ablation experiments demonstrated that the proposed method achieved an R^(2) of 0.68,indicating an improvement of approximately 10%,and an RMSE of 0.90,representing a reduction of approximately 10%.Furthermore,through the verification of label-free quantification of four NPs:hydroxyapatite(HA),titanium dioxide(TiO_(2)),silicon dioxide(SiO_(2))and silver(Ag),and we achieved a prediction performance with an R^(2) value>0.70 using Random ***,the feature analysis revealed that the composition of the PC is most significantly influenced by the incubation plasma concentration,PDI and surface modification.

关键词： nanoparticles protein corona machine learming resampling technique feature analysis

Stimulated Raman scattering microscopy with phase-controlled light focusing and aberration correction for rapid and label-free, volumetric deep tissue imaging

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Opto-Electronic Advances 2024年第9期7卷 40-52页

作者： Weiqi Wang Zhiwei Huang Optical Bioimaging Laboratory Department of Biomedical EngineeringCollege of Design and EngineeringNational University of SingaporeSingapore 117576

We report a novel stimulated Raman scattering(SRS)microscopy technique featuring phase-controlled light focusing and aberration corrections for rapid,deep tissue 3D chemical imaging with subcellular *** accomplish phasecontrolled SRS(PC-SRS),we utilize a single spatial light modulator to electronically tune the axial positioning of both the shortened-length Bessel pump and the focused Gaussian Stokes beams,enabling z-scanning-free optical sectioning in the *** incorporating Zernike polynomials into the phase patterns,we simultaneously correct the system aberrations at two separate wavelengths(~240 nm difference),achieving a~3-fold enhancement in signal-to-noise ratio over the uncorrected imaging ***-SRS provides>2-fold improvement in imaging depth in various samples(e.g.,polystyrene bead phantoms,porcine brain tissue)as well as achieves SRS 3D imaging speed of~13 Hz per volume for real-time monitoring of Brownian motion of polymer beads in water,superior to conventional point-scanning SRS 3D *** further utilize PC-SRS to observe the metabolic activities of the entire tumor liver in living zebrafish in cellsilent region,unraveling the upregulated metabolism in liver tumor compared to normal *** work shows that PCSRS provides unprecedented insights into morpho-chemistry,metabolic and dynamic functioning of live cells and tissue in real-time at the subcellular level.

关键词： SRS 3D imaging phase-controlled light focusing image aberration corrections deep tissue imaging

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 *** treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive ***,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical ***,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release *** implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose *** device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a *** density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in *** the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral *** 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 *** density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance *** 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

Phase-modulated multi-foci microscopy for rapid 3D imaging

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Photonics Research 2024年第7期12卷 1548-1555页

作者： WEIQI WANG LI GONG ZHIWEI HUANG Optical Bioimaging Laboratory Department of Biomedical EngineeringCollege of Design and EngineeringNational University of SingaporeSingapore 117576Singapore

3D imaging technology is pivotal in monitoring the functional dynamics and morphological alterations in living cells and ***,conventional volumetric imaging associated with mechanical z-scanning encounters challenges in limited 3D imaging speed with inertial ***,we present a unique phase-modulated multifoci microscopy (PM^(3)) technique to achieve snapshot 3D imaging with the advantages of extended imaging depths and adjustable imaging intervals between each focus in a rapid *** accomplish the tasks,we utilize a spatial light modulator (SLM) to encode the phases of the scattered or fluorescence light emanating from a volumetric sample and then project the multiple-depth images of the sample onto a single charge-coupled device camera for rapid 3D *** demonstrate that the PM^(3)technique provides~55-fold improvement in imaging depth in polystyrene beads phantom compared to the depth of field of the objective lens ***^(3)also enables the real-time monitoring of Brownian motion of fluorescent beads in water at a 15 Hz volume *** precisely manipulating the phase of scattered light on the SLM,PM^(3)can pinpoint the specific depth information in living zebrafish and rapidly observe the 3D dynamic processes of blood flow in the zebrafish *** work shows that the PM^(3)technique developed is robust and versatile for fast 3D dynamic imaging in biological and biomedical systems.

关键词： alterations scattered beads

Time-of-flight resolved stimulated Raman scattering microscopy using counter-propagating ultraslow Bessel light bullets generation

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Light(Science & Applications) 2024年第7期13卷 1427-1440页

作者： Shulang Lin Li Gong Zhiwei Huang Optical Bioimaging Laboratory Department of Biomedical EngineeringCollege of Design and EngineeringNational University of SingaporeSingapore 117576Singapore

We present a novel time-of-flight resolved Bessel light bullet-enabled stimulated Raman scattering(B2-SRS)microscopy for deeper tissue 3D chemical imaging with high resolution without a need for mechanical *** accomplish the tasks,we conceive a unique method to enable optical sectioning by generating the counterpropagating pump and Stokes Bessel light bullets in the sample,in which the group velocities of the Bessel light bullets are made ultraslow(e.g.,vg≈0.1c)and tunable by introducing programmable angular dispersions with a spatial light *** theoretically analyze the working principle of the collinear multicolor Bessel light bullet generations and velocity controls with the relative time-of-flight resolved detection for SRS 3D deep tissue *** have also built the B2-SRS imaging system and present the first demonstration of B2-SRS microscopy with Bessel light bullets for 3D chemical imaging in a variety of samples(e.g.,polymer bead phantoms,biological samples such as spring onion tissue and porcine brain)with high *** B2-SRS technique provides a>2-fold improvement in imaging depth in porcine brain tissue compared to conventional SRS *** method of optical sectioning in tissue using counter-propagating ultraslow Bessel light bullets developed in B2-SRS is generic and easy to perform and can be readily extended to other nonlinear optical imaging modalities to advance 3D microscopic imaging in biological and biomedical systems and beyond.

关键词： Bessel resolved propagating

Line-scanning microscopy with laterally symmetric imaging using simultaneous cross-line illumination

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Photonics Research 2024年第7期12卷 1513-1521页

作者： DAN SHEN YAFENG LI MENG WANG YUTONG HAN BOLIN LU HUI GONG QINGMING LUO JING YUAN Britton Chance Center for biomedical Photonics and MoE Key Laboratory for biomedical Photonics Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan 430074China HUST-Suzhou institute for Brainsmatics JITRI Institute for BrainsmaticsSuzhou 215123China School of biomedical engineering Hainan UniversityHaikou 570228China

Using an on-the-fly scanning scheme, line confocal microscopy can obtain complex structures of large biological tissues with high throughput. Yet, it suffers from lateral imaging asymmetry and thus introduces the potential deformations of the observation results. Here, we propose cross-line illumination microscopy (cLIM) that acquires the imaging data of two perpendicular directions simultaneously through the same objective lens in a line scanning and utilizes two-direction deconvolution fusion to achieve lateral symmetric imaging *** fluorescence beads indicates that cLIM reduces lateral resolution asymmetry from 46.1%to 2.5%and improves lateral resolution by 31.0%, compared with traditional line-scanning imaging. Compared with commercial point-confocal microscopy, the cLIM has a 25.84×increase in imaging speed and 1.93×better background-suppressing ability when imaging an 11,306μm×7783μm×100μm mouse kidney slice. We also show the advantages of the cLIM in observing direction-sensitive texture features by imaging a muscular tissue slice. cLIM offers a novel solution to achieve laterally symmetric line-scanning imaging with simple modifications while maintaining high throughput and accuracy for imaging large-scale samples.

关键词： illumination simultaneous scanning

Wireless sequential dual light delivery for programmed PDT in vivo

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Light(Science & Applications) 2024年第6期13卷 1047-1061页

作者： Jiayi Liu Bowen Sun Wenkai Li Han-Joon Kim Shu Uin Gan John S.Ho Juwita Norasmara Bte Rahmat Yong Zhang Department of Oncology The Second Xiangya HospitalCentral South UniversityChangshaHunan410011China Department of biomedical engineering College of Design and EngineeringNational University of SingaporeSingapore117585Singapore Department of Mechanical engineering College of Design and EngineeringNational University of SingaporeSingapore117576Singapore Department of Electrical and Computer engineering College of Design and EngineeringNational University of SingaporeSingapore117583Singapore Department of Medical IT Convergence engineering Kumoh National Institute of TechnologyGumi39253Republic of Korea Department of Surgery Yong Loo Lin School of MedicineNational University of SingaporeSingapore119228Singapore The N.1 institute for Health National University of SingaporeSingapore117456Singapore institute for Health Innovation and Technology National University of SingaporeSingapore119276Singapore Department of biomedical engineering College of EngineeringCity University of Hong KongKowloonHong Kong SARChina

Using photodynamic therapy(PDT)to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of *** nanocarriers are widely used for photosensitizer delivery,while the self-quenching of the encapsulated photosensitizers would impair the PDT ***,the generated short-lived reactive oxygen spieces(ROS)can hardly diffuse out of nanocarriers,resulting in low PDT ***,a smart nanocarrier system which can be degraded by light,followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy.A light-sensitive polymer nanocarrier encapsulating photosensitizer(RB-M)was *** implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded *** transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths *** irradiation time,dose,and RB-M concentration were determined using an agent-based digital simulation *** vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose,which is a clinically significant event that enhances treatment safety.

关键词： PDT overcome hardly

Nanomedicine-mediated immunogenic cell death and its combination with immune checkpoint blockade therapy

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Science China(Technological Sciences) 2024年第8期67卷 2350-2362页

作者： CHEN JunBin ZHANG YuXi SU Miao ZHU YueQiang YANG XianZhu School of biomedical Sciences and engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China national engineering Research Center for Tissue Restoration and Reconstruction Guangdong Provincial Key Laboratory of Biomedical EngineeringKey Laboratory of Biomedical Materials and Engineering of the Ministry of EducationSouth China University of TechnologyGuangzhou 510006China

Cancer immunotherapies, which train the natural immune system to specifically kill tumor cells while sparing the healthy cells,have helped revolutionize cancer treatments and demonstrated promising clinical therapeutic benefits for decades. However, the therapeutic outcome of immunotherapies, even for the most successful immune checkpoint blockade(ICB) therapy, remains unsatisfactory in the clinical practice, mainly due to the low immunogenicity of solid tumors and its immunosuppressive tumor microenvironment(TME). Notably, several cancer treatment modalities, including chemotherapy, radiotherapy, and phototherapy, have been revealed to evoke tumor immunogenicity and reverse immunosuppressive TME via inducing immunogenic cell death(ICD) of tumor cells, which synergistically sensitized tumors to ICB therapy. Nanomedicines have been extensively applied to augment ICD-inducing treatment modalities and potentiate ICB therapeutic efficacy therapy due to the opportune convergence of immunotherapy and nanotechnology. Here, we discuss the recent advances in nanomedicine-mediated ICD and its combination with ICB therapy.

关键词： cancer immunotherapy nanomedicine immunogenic cell death immune checkpoint blockade

Ultra-high spatio-temporal resolution imaging with parallel acquisition-readout structured illumination microscopy(PAR-SIM)

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Light(Science & Applications) 2024年第6期13卷 1140-1158页

作者： Xinzhu Xu Wenyi Wang Liang Qiao Yunzhe Fu Xichuan Ge Kun Zhao Karl Zhanghao Meiling Guan Xin Chen Meiqi Li Dayong Jin Peng Xi Department of biomedical engineering College of Future TechnologyPeking UniversityBeijing100871China Wallace H.Coulter Dept.of biomedical engineering Georgia Institute of Technology and Emory UniversityAtlanta30332GAUSA national biomedical Imaging Center Peking UniversityBeijing100871China Department of biomedical engineering College of EngineeringSouthern University of Science and TechnologyShenzhen518055GuangdongChina Airy Technologies Co. Ltd.Beijing100086China Eastern institute for Advanced Study Eastern Institute of TechnologyNingboZhejiang315200China School of Life Science Peking UniversityBeijing100871China institute for biomedical Materials and Devices(IBMD) Faculty of ScienceUniversity of Technology SydneySydneyNSW2007Australia

Structured illumination microscopy(SIM)has emerged as a promising super-resolution fluorescence imaging technique,offering diverse configurations and computational strategies to mitigate phototoxicity during real-time imaging of biological *** efforts to enhance system frame rates have concentrated on processing algorithms,like rolling reconstruction or reduced frame reconstruction,or on investments in costly sCMOS cameras with accelerated row readout *** this article,we introduce an approach to elevate SIM frame rates and region of interest(ROI)coverage at the hardware level,without necessitating an upsurge in camera expenses or intricate ***,parallel acquisition-readout SIM(PAR-SIM)achieves the highest imaging speed for fluorescence imaging at currently available detector *** using the full frame-width of the detector through synchronizing the pattern generation and image exposure-readout process,we have achieved a fundamentally stupendous information spatial-temporal flux of 132.9 MPixels·s^(−1),9.6-fold that of the latest techniques,with the lowest SNR of−2.11 dB and 100 nm ***-SIM demonstrates its proficiency in successfully reconstructing diverse cellular organelles in dual excitations,even under conditions of low signal due to ultra-short exposure ***,mitochondrial dynamic tubulation and ongoing membrane fusion processes have been captured in live COS-7 cell,recorded with PAR-SIM at an impressive 408 *** posit that this novel parallel exposure-readout mode not only augments SIM pattern modulation for superior frame rates but also holds the potential to benefit other complex imaging systems with a strategic controlling approach.

关键词： hardware illumination resolution