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Development of a portable reflectance confocal microscope and its application in the noninvasive in vivo evaluation of mesenchymal stem cell-promoted cutaneous wound healing

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Bio-Design and Manufacturing 2023年第3期6卷 268-283页

作者： Lixing Zhang Xin Miao Meijia Wang Aihua Shi Jingwen Wang Zhonglin Ma Yunhai Zhang Jingzhong Zhang Shuang Yu Suzhou Institute of biomedical Engineering and Technology(SIBET) Chinese Academy of SciencesSuzhou 215163China Department of biomedical Engineering School of Medical ImagingXuzhou Medical UniversityXuzhou 221004China Zhengzhou Zhongke Institute of biomedical Engineering and Technology Affiliated with SIBET Zhengzhou 450001China school of biomedical Engineering(Suzhou) Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China school of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China

The process of wound healing is routinely evaluated by histological evaluation in the clinic,which may cause scarring and secondary *** confocal microscopy(RCM)represents a noninvasive,real-time imaging technique that allows in vivo evaluation of the *** RCM was wide-probe-based,which limited its application on uneven and covered *** this study,we report the development of a portable reflectance confocal microscope(PRCM)in which all components were assembled in a handheld *** the size and weight of the PRCM were reduced based on the use of a microelectromechanical system,the resolution was kept at 0.91μm,and the field of view of the system was 343μm×532μ*** used in vivo,the PRCM was able to visualize cellular and nuclear morphology for both mouse and human *** evaluations were then performed on wounds after topically applied mesenchymal stem cells(MSCs)or saline *** PRCM allowed visualization of the formation of collagen bundles,re-epithelization from the wound edge to the wound bed,and hair follicle regeneration,which were consistent with histological ***,we offer new insights into monitoring the effects of topically applied MSCs on the process of wound healing by using *** study illustrates that the newly developed PRCM represents a promising device for real-time,noninvasive monitoring of the dynamic process of wound healing,which demonstrates its potential to diagnose,monitor,or predict disease in clinical wound therapy.

关键词： Portable reflectance confocal microscope Wound healing Noninvasive optical imaging Real-time in vivo visualization

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Engineering natural molecule-triggered genetic control systems for tunable gene-and cell-based therapies

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Synthetic and Systems Biotechnology 2023年第3期8卷 416-426页

作者： Xinyi Wang Xuantong Zhou Liping Kang Yuqin Lai Haifeng Ye Synthetic Biology and biomedical Engineering Laboratory Biomedical Synthetic Biology Research CenterShanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityDongchuan Road 500Shanghai 200241China

The ability to precisely control activities of engineered designer cells provides a novel strategy for modern precision *** adjustable gene-and cell-based precision therapies are recognized as next generation ***,the translation of these controllable therapeutics into clinical practice is severely hampered by the lack of safe and highly specific genetic switches controlled by triggers that are nontoxic and side-effect ***,natural products derived from plants have been extensively explored as trigger molecules to control genetic switches and synthetic gene networks for multiple *** controlled genetic switches could be further introduced into mammalian cells to obtain synthetic designer cells for adjustable and fine tunable cell-based precision *** this review,we introduce various available natural molecules that were engineered to control genetic switches for controllable transgene expression,complex logic computation,and therapeutic drug delivery to achieve precision *** also discuss current challenges and prospects in translating these natural molecule-controlled genetic switches developed for biomedical applications from the laboratory to the clinic.

关键词： Mammalian synthetic biology Natural molecules Genetic switches Gene-and cell-based therapy Precision medicine

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Pericyte-like differentiation of human adipose-derived mesenchymal stem cells:An in vitro study

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World Journal of Stem Cells 2020年第10期12卷 1152-1170页

作者： Giuliana Mannino Florinda Gennuso Giovanni Giurdanella Federica Conti Filippo Drago Salvatore Salomone Debora Lo Furno Claudio Bucolo Rosario Giuffrida Physiology Section Department of Biomedical and Biotechnological SciencesUniversity of CataniaCatania 95123Italy Pharmacology Section Department of Biomedical and Biotechnological SciencesSchool of MedicineUniversity of CataniaCatania 95123Italy Biochemistry Section Department of Biomedical and Biotechnological SciencesSchool of MedicineUniversity of CataniaCatania 95123Italy

BACKGROUND Adipose-derived mesenchymal stem cells(ASCs)are characterized by long-term self-renewal and a high proliferation *** adequate conditions,they may differentiate into cells belonging to mesodermal,endodermal or ectodermal *** support endothelial cells and play an important role in stabilizing the vessel wall at the microcirculation *** loss of pericytes,as occurs in diabetic retinopathy,results in a breakdown of the blood-retina barrier(BRB)and infiltration of inflammatory *** this context,the use of pericytelike differentiated ASCs may represent a valuable therapeutic strategy for restoring BRB *** To test in vitro strategies to obtain pericyte-like differentiation of human ASCs(hASCs).METHODS Different culture conditions were tested:hASCs cultured in a basal medium supplemented with transforming growth factorβ1;and hASCs cultured in a specific pericyte medium(PM-hASCs).In a further sample,pericyte growth supplement was omitted from the *** addition,cultures of human retinal pericytes(hRPCs)were used for ***-like differentiation of hASCs was tested by immunocytochemical staining and western blotting to evaluate the expression ofα-smooth muscle actin(α-SMA)and neural/glial antigen 2(NG2).Interactions between human retinal endothelial cells(hRECs)and different groups of hASCs were investigated in co-culture *** these cases,the expression of typical junctional proteins such as vascular endothelial-Cadherin,zonula occludens-1 and Occludin were assessed in *** an in vitro model of the BRB,values of trans-endothelial electrical resistance were measured when hRECs were co-cultured with various groups of pretreated *** values observed were compared with co-cultures of hRECs and hRPCs as well as with cultures of hRECs ***-dimensional co-cultures of hRECs and hRPCs or pericyte-like hASCs in Matrigel were designed to assess their reciprocal *** After 3-6 d of cult

关键词： Adipose-derived mesenchymal stem cells Pericyte-like differentiation Retinal endothelial cells Retinal pericytes Blood-retina barrier Junction proteins

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Extracellular ADP facilitates monocyte recruitment in bacterial infection via ERK signaling

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Cellular & Molecular Immunology 2018年第1期15卷 58-73页

作者： Xiaoyu Zhang Juliang Qin Junyan Zou Zhangsheng Lv Binghe Tan Jueping Shi Yihan Zhao Hua Ren Mingyao Liu Min Qian Bing Du Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiChina

As the most prominent clinical drug targets for the inhibition of platelet aggregation, P2Y12 and P2Y13 have been found to be highly expressed in both platelets and macrophages. However, the roles and function of P2Y12/13 in the regulation of macrophage-mediated innate immune responses remain unclear. Here, we demonstrate that adenosine 5′-diphosphate (ADP), the endogenous ligand of P2Y1, P2Y12 and P2Y13, was released both in E. coli-infected mice and from macrophages treated with either lipopolysaccharide (LPS) or Pam3CSK4. Furthermore, the expression of P2Y13 was clearly increased in both LPS-treated macrophages and tuberculosis patients. ADP protected mice from E. coli 0111-induced peritonitis by recruiting more macrophages to the infected sites. Consistent with this, ADP and ADP-treated cell culture medium attracted more macrophages in the transwell assay by enhancing the expression of MCP-1. Nevertheless, P2Y1 is dispensable for ADP-mediated protection against bacterial infection. However, either P2Y12/P2Y13 deficiency or blocking the downstream signaling of P2Y12/P2Y13 blocked the ADP-mediated immune response and allowed more bacteria to persist in the infected mice. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylation was clearly increased by ADP, and this type of activation could be blocked by either forskolin or analogs of cyclic AMP (cAMP) (for example, 8-bromo-cAMP). Accordingly, ADP-induced MCP-1 production and protection against bacterial infection could also be reduced by U0126, forskolin and 8-bromo-cAMP. Overall, our study reveals a relationship between danger signals and innate immune responses, which suggests the potential therapeutic significance of ADP-mediated purinergic signaling in infectious diseases.

关键词： ADP cAMP danger signal MCP-1 purinergic receptors

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Glucose metabolism in amyotrophic lateral sclerosis:it is bitter-sweet

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Neural Regeneration Research 2022年第9期17卷 1975-1977页

作者： Titaya Lerskiatiphanich Jianina Marallag John D.Lee school of biomedical sciences Faculty of MedicineThe University of QueenslandSt LuciaBrisbaneQLDAustralia

A recent study by McDonald et al.(2021)focused on how peripheral glucose metabolism and handling are compromised in amyotrophic lateral sclerosis(ALS).Dysfunctions in glucose and energy metabolism have been identified in transgenic mouse models and patients with ***,how these processes are altered and contribute to disease progression are not fully *** aforementioned study has identified several changes to glucose homeostasis in the transgenic SOD1G93A mouse model of ALS at the later stages of the ***,the authors found that despite insulin resistance being present,there was increased glucose uptake in ALS mice,and increased glycogen accumulation in the ***,there was evidence of glucagon resistance developing in these mice,which supports clinical *** perspective outlines the key aspects of glucose metabolism and demonstrates how multiple pathways relating to these processes are compromised in ALS.

关键词： metabolism amyotrophic homeostasis

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Surface effects of liquid metal amoeba

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Science Bulletin 2017年第10期62卷 700-706页

作者： Liang Hu Jing Li Jianbo Tang Jing Liu Beijing Key Laboratory of Cryo-biomedical Engineering and Key Laboratory of Cryogenics Technical Institute of Physics and Chemistry Chinese Academy of Sciences Department of biomedical Engineering School of Medicine Tsinghua University

Liquid metals(LM) such as eutectic gallium-indium and gallium-indium-tin are important functional liquid-state metal materials with many unique properties, which have attracted wide attentions especially from soft robot area. Recently the amoeba-like transformations of LM on the graphite surface are discovered, which present a promising future for the design and assemble of self-fueled actuators with dendritically deformable body. It appears that the surface tension of the LM can be significantly reduced when it contacts graphite surface in alkaline solution. Clearly, the specific surface should play a vital role in inducing these intriguing behaviors, which is valuable and inspiring in soft robot design. However, the information regarding varied materials functions underlying these behaviors remains unknown. To explore the generalized effects of surface materials in those intriguing behavior, several materials including glass, graphite, nickel and copper oxides(CuO) were comparatively investigated as substrate *** results were obtained that only LM amoeba transformations were observed on graphite and CuO surfaces. In order to identify the proper surface condition for LM transformation, the intrinsic properties of substrate surfaces, such as the surface charge and roughness, as well as the specific interaction with LM like wetting behavior and mutual locomotion etc., were characterized. The integrated results revealed that LM droplet appears more likely to deform on surfaces with higher positive surface charge density, higher roughness and less bubble generation on them. In addition, another surface material,CuOx, is identified to own similar ability to graphite, which is valuable in achieving amoeba-like transformation. Moreover, this study offers a fundamental understanding of the surface properties in realizing LM amoeba transformations, which would shed light on packing and structure design of liquid metal-based soft device within multi-material s

关键词： Surface effect Liquid metal amoeba Surface tension Substrate materials

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The In-situ Reinforcement of Calcium Phosphate Cement and Its Micro-structural Analysis

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Journal of Wuhan University of Technology(Materials Science) 2005年第B12期20卷 19-21页

作者：万鹏 Institute of Analytical and biomedical sciences School of Chemistry and Molecular Sciences Wuhan University Wuhan 430072 China

Carbon nanotubes （ CNTs ） and polyacrylic acid were employed to modify the setting process and hydration products of β-TCP/TTCP calcium phosphate cement. The micro-structure of hydration product and the fashion of how additives and hydration particles interconnected were investigated. With the modification effect of CNTs , the setting particles and CNTs got winded and interconnected and thus made the composite more compact and denser.

关键词： calcium phosphate cement CNTs polyacrylic acid microstructure

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Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases

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World Journal of Stem Cells 2021年第6期13卷 632-644页

作者： Giuliana Mannino Cristina Russo Anna Longo Carmelina Daniela Anfuso Gabriella Lupo Debora Lo Furno Rosario Giuffrida Giovanni Giurdanella Department of biomedical and Biotechnological sciences School of MedicineUniversity of CataniaCatania 95123Italy

Stem cell-based treatments have been extensively explored in the last few decades to develop therapeutic strategies aimed at providing effective alternatives for those human pathologies in which surgical or pharmacological therapies produce limited *** stem cells of different sources,mesenchymal stem cells(MSCs)offer several advantages,such as the absence of ethical concerns,easy harvesting,low immunogenicity and reduced tumorigenesis *** than a multipotent differentiation ability,MSCs can release extracellular vesicles conveying proteins,mRNA and *** to these properties,new therapeutic approaches have been designed for the treatment of various pathologies,including ocular *** this review,the use of different MSCs and different administration strategies are described for the treatment of diabetic retinopathy,glaucoma,and retinitis *** a large number of investigations,positive results have been obtained by in vitro experiments and by MSC administration in animal *** authors agree that beneficial effects are likely related to MSC paracrine *** on these considerations,many clinical trials have already been carried ***,although some adverse effects have been described,promising outcomes are *** can be assumed that in the near future,safer and more effective protocols will be developed for more numerous clinical applications to improve the quality of life of patients affected by eye diseases.

关键词： Mesenchymal stem cells Eye diseases Diabetic retinopathy Glaucoma Retinitis pigmentosa Regenerative medicine

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A highly conductive and stretchable wearable liquid metal electronic skin for long-term conformable health monitoring

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Science China(Technological sciences) 2018年第7期61卷 1031-1037页

作者： GUO Rui WANG XueLin YU WenZhuo TANG JianBo LIU Jing Department of biomedical Engineering School of Medicine Tsinghua University Beijing Key Lab of Cryo biomedical Engineering and Key Lab of Cryogenics Technical Institute of Physics and Chemistry Chinese Academy of Sciences

Conventional rigid electronics are usually unconformable with soft skins and tend to fail in accurate physiological monitoring and precise treatment. Electronic skins(e-Skins) made by conductive and stretchable materials offer mechanical compliance for fabricating flexible and conformable wearables. Compared to common organic or inorganic conductive materials, gallium-based liquid metals alone own superior conductivity and compliance. Here, we demonstrate a highly conductive and stretchable electronic skin with liquid metal circuits(LMCs) embedded in silicone rubber film, which are functionalized for physiological signals monitoring. Through the designs of serpentine structure, LMCs maintained good electrical conductivity and functionality under over 100% strain. Also, a wearable electrocardiogram(ECG) recording device was fabricated and tested. The device was able to acquire steady signals during real-time measurement of physical activities. The proposed liquid metal e-Skin can be further extended to conformable bio-integrated healthcare devices and intelligent health monitoring networks.

关键词： EGaln liquid metal circuit flexible electronics wearable e-Skin health monitoring

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Transparent soft PDMS eggshell

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Science China(Technological sciences) 2015年第2期58卷 273-283页

作者： LAI YiYu LIU Jing Department of biomedical Engineering School of Medicine Tsinghua University Beijing Key Laboratory of Cryo biomedical Engineering and Key Laboratory of Cryogenics Technical Institute of Physics and ChemistryChinese Academy of Sciences

In vivo 3D fluorescent image remains a technological barrier for biologists and clinical scientists although green fluorescent protein(GFP)imaging has long been performed rather well at cellular ***,robust enough portable devices are also challenging lab-on-a-chip advocators who wish their designs to be nurtured by the end *** work is dedicated to propose a conceptually innovated transparent soft PDMS avian eggshell to directly tackle the above two ***,an"egg-on-a-chip"scheme is originally developed and demonstrated by a newly developed PDMS"soft"process *** its ancestor–the conventional"lab-on-a-chip"(LOC)which is basically chemically based,the current"egg-on-a-chip",intrinsically inherited with biological natures,opens a way to integrate biological parts or whole system in a miniature sized *** biomimics system contains much condensed environmental evolutional tensor inside than those of the existing LOC compacted with artificial components which however are quite difficult to incorporate various life factors *** unique advantages,a series of transparent PDMS whole"eggshells"have been fabricated and applied to culture avian embryos up to 17.5 days and chimeric eggshells were engineered on normal *** addition,X-stage embryos were successfully initiated in such system and pre-chorioallantoic membrane was ***,limitation of the present process was interpreted and potential approach to improve it was *** both high optical transparency and engineering subtlety fully integrated together,the present method not only provides an ideal transparent imaging platform for studying functional embryo development including life mystery,but also promises a future strategy for"lab-on-an-egg"technology which may be important in a wide variety of either fundamental or practical areas.

关键词： soft PDMS process method biological mould egg-on-a-chip portable device pre-chorioallantoic membrane biomimics

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