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Regenerative capacity of Müller cells and their modulation as a tool to treat retinal degenerations

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Neural Regeneration Research 2023年第1期18卷 139-140页

作者： Federica M.Conedera Volker Enzmann Advanced Microscopy Program Center for Systems BiologyMassachusetts General HospitalBostonMAUSA wellman center for photomedicine Massachusetts General HospitalBostonMAUSA(Conedera FM)Department of OphthalmologyUniversity HospitalUniversity of BernBernSwitzerland Department of BioMedical Research University of BernBernSwitzerland

Vision is one of our most precious senses,and its impairment has a high socio-economic impact.In the industrialized world,degenerative diseases of the retina lead to vision loss,particularly among the elderly.These degenerations include,for instance,retinitis pigmentosa,age-related macular degeneration,and diabetic retinopathy.Although treatments are evolving to manage late-stage symptoms of retinal degenerations,no effective therapies to recover vision loss exist.Retinal degeneration often involves loss or damage to specialized neural cells,such as photoreceptors,and their death stimulates the activation and proliferation of Müller cells(Salman et al.,2021).

关键词： degeneration diseases impairment

Supramolecular hybrid hydrogels as rapidly on-demand dissoluble,self-healing,and biocompatible burn dressings

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Bioactive Materials 2023年第7期25卷 415-429页

作者： A.Aslihan Gokaltun Letao Fan Luca Mazzaferro Delaney Byrne Martin L.Yarmush Tianhong Dai Ayse Asatekin O.Berk Usta center for Engineering in Medicine and Surgery Massachusetts General HospitalHarvard Medical School55 Fruit St.BostonMA02114USA Shriners hospitals for Children 51 Blossom St.BostonMA02114USA Department of Chemical and Biological Engineering Tufts University4 Colby St.MedfordMA02474USA Department of Chemical Engineering Hacettepe University06532BeytepeAnkaraTurkey Department of Biomedical Engineering Rutgers University599 Taylor Rd.PiscatawayNJ08854USA wellman center for photomedicine Massachusetts General HospitalDepartment of DermatologyHarvard Medical School50 Blossom StreetBostonMA02114USA

Despite decades of efforts,state-of-the-art synthetic burn dressings to treat partial-thickness burns are still far from ideal.Current dressings adhere to the wound and necessitate debridement.This work describes the first“supramolecular hybrid hydrogel(SHH)”burn dressing that is biocompatible,self-healable,and on-demand dissoluble for easy and trauma-free removal,prepared by a simple,fast,and scalable method.These SHHs leverage the interactions of a custom-designed cationic copolymer via host-guest chemistry with cucurbit[7]uril and electrostatic interactions with clay nanosheets coated with an anionic polymer to achieve enhanced mechanical properties and fast on-demand dissolution.The SHHs show high mechanical strength(>50 kPa),self-heal rapidly in~1 min,and dissolve quickly(4-6 min)using an amantadine hydrochloride(AH)solution that breaks the supramolecular interactions in the SHHs.Neither the SHHs nor the AH solution has any adverse effects on human dermal fibroblasts or epidermal keratinocytes in vitro.The SHHs also do not elicit any significant cytokine response in vitro.Furthermore,in vivo murine experiments show no immune or inflammatory cell infiltration in the subcutaneous tissue and no change in circulatory cytokines compared to sham controls.Thus,these SHHs present excellent burn dressing candidates to reduce the time of pain and time associated with dressing changes.

关键词： Supramolecular hybrid hydrogels Cationic copolymer On-demand dissoluble Self-healable Biocompatible Burn injury

A Comparative Study on the Enhancement Efficacy of Specific and Non-specific Iron Chelators for Protoporphyrin Ⅸ Production and Photosensitization in HaCat Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第6期29卷 765-770页

作者：夏育民黄樱樱林隆德刘小明江珊熊腊元 Department of Dermatology Renmin Hospital of Wuhan University Aesthetic and Plastic center of Guangxi Medical University wellman center for photomedicine Massachusetts General Hospital Harvard Medical School School of Public Health Guangxi Medical University

The iron chelators can be utilized in target cells to improve 5-aminolaevulinic acid （ALA）-based photodynamic therapy （PDT）. The purpose of this study is to compare the effect of two kinds of iron chelators, desferrioxamine （DFO） and ethylenediaminetetraacetic acid （EDTA） on the enhancement of ALA-PDT. HaCat cells were cultured in medium containing 2.0 mmol/L of ALA and 0.5 mmol/L of DFO or EDTA. After 3-h incubation in the dark, the concentration of cellular pro-toporphyrin Ⅸ （PpⅨ） was detected by high performance liquid chromatography （HPLC）, and the fluorescence of PpⅨ was observed at 630 nm emission under confocal laser scanning microscope. For PDT, HaCat cells were irradiated using 632.8 nm laser, and the fractions of apoptotic and necrotic cells were flow cytometrically assayed. Related differences in morphology and ultrastructure of Ha-Cat cells were observed using optical microscope or transmission electron microscope. Compared to incubation with ALA alone, the addition of DFO or EDTA increased the concentration of cellular PpⅨ and the fluorescent density of PpⅨ, and also increased cell death ratio after PDT. PDT using ALA plus DFO produced the highest cellular PpⅨ level, greatest cell death ratio and most severe structural damage to the cells. It was concluded that both DFO and EDTA could enhance ALA-based PpⅨ production and PDT. Compared to the non-specific iron chelator of EDTA, the specific chelator, DFO, showed more potential for the enhancement.

关键词： aminolaevulinic acid desferrioxamine ethylenediaminetetraacetic acid keratinocytes photodynamic therapy protoporphyrin Ⅸ

Laser particles with omnidirectional emission for cell tracking

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Light(Science & Applications) 2021年第2期10卷 197-207页

作者： Shui-Jing Tang Paul H.Dannenberg Andreas C.Liapis Nicola Martino Yue Zhuo Yun-Feng Xiao Seok-Hyun Yun Harvard Medical School and wellman center for photomedicine Massachusetts General HospitalBostonMAUSA State Key Laboratory for Mesoscopic Physics and Frontiers Science center for Nano-optoelectronics School of PhysicsPeking University100871 BeijingChina Harvard-MIT Health Sciences and Technology Massachusetts Institute of TechnologyCambridgeMAUSA

The ability to track individual cells in space over time is crucial to analyzing heterogeneous cell populations.Recently,microlaser particles have emerged as unique optical probes for massively multiplexed single-cell tagging.However,the microlaser far-field emission is inherently direction-dependent,which causes strong intensity fluctuations when the orientation of the particle varies randomly inside cells.Here,we demonstrate a general solution based on the incorporation of nanoscale light scatterers into microlasers.Two schemes are developed by introducing either boundary defects or a scattering layer into microdisk lasers.The resulting laser output is omnidirectional,with the minimum-to-maximum ratio of the angle-dependent intensity improving from 0.007(-24 dB)to>0.23(-6dB).After transfer into live cells in vitro,the omnidirectional laser particles within moving cells could be tracked continuously with high signal-to-noise ratios for 2 h,while conventional microlasers exhibited frequent signal loss causing tracking failure.

关键词： scattering directional intensity

3D cellular-resolution imaging in arteries using few-mode interferometry

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Light(Science & Applications) 2019年第1期8卷 183-191页

作者： Biwei Yin Zhonglie Piao Kensuke Nishimiya Chulho Hyun Joseph A.Gardecki Adam Mauskapf Farouc A.Jaffer Guillermo J.Tearney wellman center for photomedicine Harvard Medical School and Massachusetts General HospitalBostonMA 02114USA Cardiovascular Research center and Cardiology Division Harvard Medical School and Massachusetts General HospitalBostonMA 02114USA Department of Pathology Harvard Medical School and Massachusetts General HospitalBostonMA 02114USA Harvard-MIT Division of Health Sciences and Technology CambridgeMA 02139USA

Cross-sectional visualisation of the cellular and subcellular structures of human atherosclerosis in vivo is significant,as this disease is fundamentally caused by abnormal processes that occur at this scale in a depth-dependent manner.However,due to the inherent resolution-depth of focus tradeoff of conventional focusing optics,today’s highestresolution intravascular imaging technique,namely,optical coherence tomography(OCT),is unable to provide crosssectional images at this resolution through a coronary catheter.Here,we introduce an intravascular imaging system and catheter based on few-mode interferometry,which overcomes the depth of focus limitation of conventional highnumerical-aperture objectives and enables three-dimensional cellular-resolution intravascular imaging in vivo by a submillimetre diameter,flexible catheter.Images of diseased cadaver human coronary arteries and living rabbit arteries were acquired with this device,showing clearly resolved cellular and subcellular structures within the artery wall,such as individual crystals,smooth muscle cells,and inflammatory cells.The capability of this technology to enable cellularresolution,cross-sectional intravascular imaging will make it possible to study and diagnose human coronary disease with much greater precision in the future.

关键词： arteries rabbit resolution

Efficient dispersion modeling in optical multimode fiber

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Light(Science & Applications) 2023年第2期12卷 194-206页

作者： Szu-Yu Lee Vicente J.Parot Brett E.Bouma Martin Villiger Harvard Medical School and massachusetts general hospital Wellman Center for PhotomedicineBostonMA 02114USA Harvard-MIT Health Sciences and Technology Massachusetts Institute of TechnologyCambridgeMA 02140USA Institute for Biological and Medical Engineering Pontificia Universidad Catolica de ChileSantiago 7820244Chile institute for Medical Engineering and Science Massachusetts Institute of TechnologyCambridgeMA 02140USA

Dispersion remains an enduring challenge for the characterization of wavelength-dependent transmission through optical multimode fiber(MMF).Beyond a small spectral correlation width,a change in wavelength elicits a seemingly independent distribution of the transmitted field.Here we report on a parametric dispersion model that describes mode mixing in MMF as an exponential map and extends the concept of principal modes to describe the fiber's spectrally resolved transmission matrix(TM).We present computational methods to fit the model to measurements at only a few,judiciously selected,discrete wavelengths.We validate the model in various MMF and demonstrate an accurate estimation of the full TM across a broad spectral bandwidth,approaching the bandwidth of the best-performing principal modes,and exceeding the original spectral correlation width by more than two orders of magnitude.The model allows us to conveniently study the spectral behavior of principal modes,and obviates the need for dense spectral measurements,enabling highly effcient reconstruction of the multispectral TM of MMF.

关键词： fiber optical dispersion

Laser facilitates vaccination

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Journal of Innovative Optical Health Sciences 2016年第1期9卷 12-20页

作者： Ji Wang Peiyu Li Xinyuan Chen Mei X.Wu wellman center for photomedicine massachusetts general hospital and Department of Dermotology Harvard Medical SchoolBostonMA 02114USA Biomedical and Pharmaceutical Science College of Pharmacy University of Rhode IslandKingstonRI 02881USA

Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces:to improve vaccine efficacy without compromising safety.Harnessing the specific effects of laser on biological systems,a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way.The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical e®ects with no foreign chemicals administered into the body.Here,we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

关键词： Laser vaccine delivery adjuvant

Color-selective holographic retroreflector array for sensing applications

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Light(Science & Applications) 2016年第1期5卷 241-249页

作者： Rajib Ahmed Ali K Yetisen Seok Hyun Yun Haider Butt Microengineering and Nanotechnology Laboratory School of EngineeringUniversity of BirminghamBirmingham B152TTUK Harvard Medical School and wellman center for photomedicine Massachusetts General HospitalCambridgeMA 02139USA Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of TechnologyCambridgeMA 02139USA

Corner cube retroreflectors(CCRs)have applications in sensors,image processing,free space communication and wireless networks.The ability to construct low-loss wavelength filters embedded in CCRs can enable the development of wavelength multiplexing,tunable lasers and photonic integrated circuits.Here we created an~10-μm-thick holographic corner cube retroreflector(HCCR)array that acted as a color-selective wavelength filter and diffracted light at broad angles.Angle-resolved spectral measurements showed that the Bragg peak of the diffracted light from the HCCR array could be tuned from 460 to 545 nm by varying the incident angle.The HCCR array also exhibited a wavelength-selective tuning capability based on the rotation angle in the visible spectrum.HCCRs projected holographic images with the rotational property in the far field.The utility of the HCCR was demonstrated as optical temperature and relative humidity sensors that produced a visible colorimetric response for rapid diagnostics.

关键词： Bragg gratings corner cube retroreflectors diffraction optics holography sensors

Multiplexed laser particles for spatially resolved single-cell analysis

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Light(Science & Applications) 2019年第1期8卷 526-530页

作者： Sheldon J.J.Kwok Nicola Martino Paul H.Dannenberg Seok-Hyun Yun Harvard Medical School and wellman center for photomedicine Massachusetts General Hospital50 Blossom StreetBostonMA 02114USA Harvard-MIT Health Sciences and Technology Massachusetts Institute of Technology77 Massachusetts AvenueCambridgeMA 02139USA LASE Innovation Inc. 650 E.Kendall Street2nd FLCambridgeMA 02142USA

Biomolecular analysis at the single-cell level is increasingly important in the study of cellular heterogeneity and its consequences,particularly in organismic development and complex diseases such as cancer.Single-cell molecular analyses have led to the identification of new cell types1 and the discovery of novel targets for diagnosis and therapy2.While these analyses are performed predominantly on dissociated single cells,emerging techniques seek understanding of cellular state,cellular function and cell–cell interactions within the native tissue environment by combining optical microscopy and single-cell molecular analyses.These techniques include in situ multiplexed imaging of fluorescently labeled proteins and nucleotides,as well as low-throughput ex vivo methods in which specific cells are isolated for downstream molecular analyses.However,these methods are limited in either the number and type of molecular species they can identify or the number of cells that can be analyzed.High-throughput methods are needed for comprehensive profiling of many cells(>1000)to detect rare cell types,discriminate relevant biomarkers from intrinsic population noise,and reduce the time and cost of measurement.Many established,highthroughput single-cell analyses are not directly applicable because they require tissue dissociation,leading to a loss of spatial information3.No current methods exist that can seamlessly connect spatial mapping to single-cell techniques.In this Perspective,we review current methods for spatially resolved single-cell analysis and discuss the prospect of novel multiplexed imaging probes,called laser particles,which allow individual cells to be tagged in tissue and analyzed subsequently using high-throughput,comprehensive single-cell techniques.

关键词： diagnosis spatially resolved