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A bioactive material with dual integrin-targeting ligands regulates specific endogenous cell adhesion and promotes vascularized bone regeneration in adult and fetal bone defects

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Bioactive Materials 2023年第2期20卷 179-193页

作者： Dake Hao ruiwu liu Tomas Gonzalez Fernandez Christopher Pivetti Jordan Elizabeth Jackson Edwin Samuel Kulubya Hong-Jiang Jiang Hai-Yang Ju Wen-Liang liu Alyssa Panitch Kit S.Lam JKent Leach Diana L.Farmer Aijun Wang Department of Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States Institute for Pediatric Regenerative Medicine Shriners Hospitals for ChildrenSacramentoCA95817United States Department of Biochemistry and Molecular Medicine School of MedicineUniversity of California DavisSacramentoCA95817United States Department of Biomedical Engineering University of California DavisDavisCA95616United States Wendeng Orthopaedic Hospital No.1 Fengshan RoadWendeng264400ShandongChina Department of Orthopaedic Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States

Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone ***,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative ***,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone *** biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,*** an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)*** a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse *** innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.

关键词： Integrin-based ligands Endogenous stem cells Bone formation Vascularization Adult and fetal bone defects

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Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing

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Bioactive Materials 2022年第4期7卷 460-473页

作者： Siqi He Tanaya Walimbe Hongyuan Chen Kewa Gao Priyadarsini Kumar Yifan Wei Dake Hao ruiwu liu Diana L.Farmer Kit S.Lam Jianda Zhou Alyssa Panitch Aijun Wang Department of Burns and Plastic Surgery The Third Xiangya Hospital of Central South UniversityChina Department of Surgery UC DavisUnited States Department of Biomedical Engineering UC DavisUnited States Department of Biochemistry and Molecular Medicine UC DavisUnited States Institute for Pediatric Regenerative Medicine Shriners Hospitals for Children Northern CaliforniaUnited States

Diabetic ischemic wound treatment remains a critical clinical *** plays a significant role in wound healing during all stages of the tissue repair *** that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds,particularly diabetic wounds in highly ischemic *** previously identified a cyclic peptide LXW7 that specifically binds to integrinαvβ3 on endothelial progenitor cells(EPCs)and endothelial cells(ECs),activates vascular endothelial growth factor(VEGF)receptors,and promotes EC growth and *** this study,we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides(SILY)to a dermatan sulfate(DS)glycosaminoglycan backbone,named LXW7-DS-SILY,and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix(ECM)*** confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic *** applied in an established Zucker Diabetic Fatty(ZDF)rat ischemic skin flap model,LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing,enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic ***,this study provides a promising novel treatment to accelerate diabetic ischemic wound healing,thereby reducing limb amputation and mortality of diabetic patients.

关键词： Diabetic ischemic wound ECM scaffold Endothelial progenitor cells Neovascularization Wound healing

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A bio-instructive parylene-based conformal coating suppresses thrombosis and intimal hyperplasia of implantable vascular devices

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Bioactive Materials 2023年第10期28卷 467-479页

作者： Dake Hao Jonathan Lin ruiwu liu Christopher Pivetti Kaeli Yamashiro Linda M.Schutzman Junichiro Sageshima Mimmie Kwong Nataliya Bahatyrevich Diana L.Farmer Misty D.Humphries Kit S.Lam Alyssa Panitch Aijun Wang Department of Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States Institute for Pediatric Regenerative Medicine Shriners Hospitals for ChildrenSacramentoCA95817United States Department of Biochemistry and Molecular Medicine School of MedicineUniversity of California DavisSacramentoCA95817United States Wallace H.Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory UniversityAtlant1GA30332United States Department of Biomedical Engineering University of California DavisDavisCA95616United States

Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable “living” endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of “off-the-shelf” implantable vascular devices for long-lasting performance in the clinical settings.

关键词： Parylene coating Integrin ligand Thrombosis Intimal hyperplasia Implantable vascular devices

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Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one- compound peptide libraries

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Cellular & Molecular Immunology 2017年第3期14卷 308-318页

作者： Nicki YH Leung Christine YY Wai Marco HK Ho ruiwu liu Kit S Lam Jin Jun Wang Shang An Shu Ka Hou Chu Patrick SC Leung School of Life Sciences The Chinese University of Hong Kong Shatin N.T. Hong Kong SAR China Department of Pediatrics and Adolescent Medicine Queen Mary Hospital The University of Heng Kong Pokfulam Hong Kong SAR China Department of Biochemistry and Molecular Medicine University of California Davis CA 95616 USA Division of Rheumatology/Allergy School of Medicine University of California Davis CA 95616 USA

The one-bead-one-compound （OBOC） combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E （IgE） epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope. This study pioneers the successful application of the OBOC libraries using whole sera to screen and identify multiple shrimp allergen mimotopes and validates their mimicry potential using in vitro, in vivo, and in silico methods.

关键词： epitope mimotope OBOC peptide library tropomyosin

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3,4-二氢-海南新碱类似物的合成及抗溃疡作用

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药学学报 1998年第9期33卷 682-687页

作者：刘瑞武高由松张守仁梁晓天中国医学科学院中国协和医科大学药物研究所

为考察３，４二氢海南新碱类似物Ｃ１取代基对化合物抗溃疡活性的影响，设计并合成了１３对共２６个新的３，４二氢海南新碱类似物，Ａ，Ｂ互为非对映异构体，大部分化合物在大鼠冷应激溃疡模型中有一定的抗溃疡活性，其中ＩＸ... 详细信息

为考察３，４二氢海南新碱类似物Ｃ１取代基对化合物抗溃疡活性的影响，设计并合成了１３对共２６个新的３，４二氢海南新碱类似物，Ａ，Ｂ互为非对映异构体，大部分化合物在大鼠冷应激溃疡模型中有一定的抗溃疡活性，其中ＩＸ３Ａ，ＩＸ７Ａ，ＩＸ８Ａ，ＩＸ１２Ａ，ＩＸ１２Ｂ，ＩＸ１３Ａ６个化合物表现较强活性，超过西咪替丁。

关键词：海南新碱类似物抗溃疡构效关系

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基于共聚焦拉曼光谱的“一珠一化合物”肽库的单珠定量负载研究

基于共聚焦拉曼光谱的“一珠一化合物”肽库的单珠定量负载研究

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第十届全国化学生物学学术会议

作者：唐浴尘 Yann Thillier ruiwu liu Xiaocen Li Kit S.Lam 高婷娟华中师范大学化学学院华中师范大学化学生物学与农药有机教育部重点实验室 Department of Biochemistry and Molecular Medicine University of California at Davis

"一珠一化合物"的组合化学方法被证明是寻找具有靶向功能的合成分子如多肽等的强有效途径。然而,很多时候一些初始筛选得到的阳性珠,重新合成后不再呈阳性,其原因有如下几个:1)解码错误,2)微量的杂质造成假阳性,3)单珠上化合物的较高负... 详细信息

"一珠一化合物"的组合化学方法被证明是寻找具有靶向功能的合成分子如多肽等的强有效途径。然而,很多时候一些初始筛选得到的阳性珠,重新合成后不再呈阳性,其原因有如下几个:1)解码错误,2)微量的杂质造成假阳性,3)单珠上化合物的较高负载（产率）使得结合效率被过高估计。为了应对这个挑战,我们发明了一种定量分析方法确定"一珠一化合物"肽库的单珠负载。这种方法的原理基于单珠上多肽N-端氨基的量与对其标记的特异信号分子的拉曼光谱强度呈正比关系。我们采用共聚焦拉曼光谱来表征有确定多肽序列的树脂珠和"一珠一化合物"的组合肽库的单珠多肽负载分布。实验结果表明,不同于起始原料TentaGel树脂珠和有确定序列的多肽树脂珠上氨基量的狭窄分布,肽库的单珠负载分布大幅变宽,尤其是对于序列较长的多肽库,这种现象更为明显。通过对肽库的负载分布（最大值/分布宽度）的定量表征,这种方法可用于监测和评价肽库的合成质量,并为深入了解"一珠一化合物"固相合成的复杂性和后续筛选的准确性提供有效的证据。

关键词： "一珠一化合物"组合化学肽库固相合成单珠定量检测共聚焦拉曼光谱

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基于FGF2的新型抗肿瘤小分子短肽的研发

基于FGF2的新型抗肿瘤小分子短肽的研发

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中国生物工程学会第二届青年科技论坛暨首届青年工作委员会学术年会

作者：陈小佳欧阳曼王海龙管文华 ruiwu liu Kit.S Lam 洪岸暨南大学生物医药研究院&暨南大学细胞生物学系基因组药物国家工程研究中心广东省生物工程药物重点实验室 Department of Biochemistry and Molecular Medicine University of California Davis University of California Davis NCI-designated Comprehensive Cancer Center

成纤维细胞生长因子受体(Fibroblast growth factor receptors,FGFRs)是酪氨酸激酶受体家族的重要成员,包括FGFR1,FGFR2,FGFR3,FGFR4和FGFRL1等。它们在肿瘤的发生发展中也扮演着关键的作用,因此也是非常重要的靶点。为开发靶向FGFR2的...

成纤维细胞生长因子受体(Fibroblast growth factor receptors,FGFRs)是酪氨酸激酶受体家族的重要成员,包括FGFR1,FGFR2,FGFR3,FGFR4和FGFRL1等。它们在肿瘤的发生发展中也扮演着关键的作用,因此也是非常重要的靶点。为开发靶向FGFR2的小分子短肽,依据FGF2的生物学活性特点,我们采用生物软件

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多基线数字近景摄影测量系统测树方法及数据分析

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林业科学 2010年第2期46卷 166-170页

作者：刘千里李春友孟平柳瑞武张劲松高峻河北农业大学园林与旅游学院保定071000 中国林业科学研究院林业研究所北京100091

Based on the measurement principle of multi-baseline digital close-range photogrammetry system,this paper proposed method of gain forest measurement factors by this system. Through comparing research of the statistical results in photogrammetry data of stumpage and measured data of total station,the result indicates that people may gain more reliable data by multi-baseline digital close-range photogrammetry system,accurately monitor forest and meet the need of forest measurement by this system. At the same time,by establishing three-dimension point cloud model based on 3-D model of tree,people may expediently gain forest measurement factors which shall be harder by traditional methods.

关键词：多基线数字近景摄影测量数据分析测树

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一珠二化合物组合化学法合成喹唑啉酮类化学库及其抗肺癌活性的初步筛选

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汕头大学医学院学报 2021年第1期34卷 1-6页

作者：王琼郑锦鸿王锦芝刘瑞武汕头大学医学院化学教研室广东汕头515041 加州大学戴维斯分校生物化学和分子医药系加利福尼亚戴维斯95817

目的:探讨一珠二化合物组合化学库结合高通量筛选的方法,为了获得小分子多靶点新型2-喹唑啉酮先导化合物以阻断肺癌的发生及发展进程。方法:以四功能分子骨架N-Alloc-3-氨基-3-(2-氟-5-硝基苯)丙酸为模板,合成具有分子多样性的喹唑啉酮... 详细信息

目的:探讨一珠二化合物组合化学库结合高通量筛选的方法,为了获得小分子多靶点新型2-喹唑啉酮先导化合物以阻断肺癌的发生及发展进程。方法:以四功能分子骨架N-Alloc-3-氨基-3-(2-氟-5-硝基苯)丙酸为模板,合成具有分子多样性的喹唑啉酮化学库;以免疫细胞化学法对肺癌细胞株H1975进行高通量筛选。结果:合成了容量为800个小分子化合物的喹唑啉酮化合库,经高通量筛选得到阳性化合物CA10。结论:CA10表现较好的抑制肺癌细胞活性,可作为先导化合进行进一步优化结构。

关键词：喹唑啉酮组合化学肺癌

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塔吊底座与钢结构转换平台栓焊混合连接设计

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浙江建筑 2015年第6期32卷 9-12页

作者：刘瑞武金虎吉红波邢国然浙江佳汇建筑设计股份有限公司浙江绍兴312000 华润新鸿基房地产(杭州)有限公司浙江杭州310020 浙江中成建工集团有限公司浙江绍兴312000

QT80A塔吊基础节底座比较特殊,采取与钢格构柱端部转换平台栓焊混合连接形成一体。通过采用ANSYS有限元软件计算评估塔吊基础节底座安全性,以充分保证塔吊设备安全可靠投入施工应用。

关键词：底座连接设计有限元分析

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