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  1. Article: Tuning the intentional corona of cerium oxide nanoparticles to promote angiogenesis via fibroblast growth factor 2 signalling.

    Fu, Lu / Li, Rupeng / Whitelock, John M / Lord, Megan S

    Regenerative biomaterials

    2022  Volume 9, Page(s) rbac081

    Abstract: Inadequate angiogenesis is a hallmark of conditions including cardiovascular diseases, stroke and chronic diabetic wounds, which exhibit tissue ischaemia ensuring that therapeutic strategies to promote angiogenesis are of great interest. However, many ... ...

    Abstract Inadequate angiogenesis is a hallmark of conditions including cardiovascular diseases, stroke and chronic diabetic wounds, which exhibit tissue ischaemia ensuring that therapeutic strategies to promote angiogenesis are of great interest. However, many angiogenic treatments involve the delivery of growth factors which have limited clinical success due to poor stability, high manufacturing cost and poor efficacy. Cerium oxide nanoparticles (nanoceria) can either promote or inhibit angiogenesis depending on their surface corona chemistry. Here, nanoceria were functionalized with an intentional heparin corona, a polysaccharide which binds and signals growth factors, of different chain lengths and surface grafting density to establish their effect on angiogenesis. These nanoparticles promoted angiogenesis
    Language English
    Publishing date 2022-10-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2799042-4
    ISSN 2056-3426 ; 2056-3418
    ISSN (online) 2056-3426
    ISSN 2056-3418
    DOI 10.1093/rb/rbac081
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  2. Article: Editorial: Roles of Chondroitin Sulfate and Dermatan Sulfate as Regulators for Cell and Tissue Development.

    Mizumoto, Shuji / Kwok, Jessica C F / Whitelock, John M / Li, Fuchuan / Perris, Roberto

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 941178

    Language English
    Publishing date 2022-06-08
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.941178
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  3. Article ; Online: Recombinant perlecan domain V covalently immobilized on silk biomaterials via plasma immersion ion implantation supports the formation of functional endothelium.

    Lau, Kieran / Fu, Lu / Zhang, Anyu / Akhavan, Behnam / Whitelock, John / Bilek, Marcela M / Lord, Megan S / Rnjak-Kovacina, Jelena

    Journal of biomedical materials research. Part A

    2023  Volume 111, Issue 6, Page(s) 825–839

    Abstract: Strategies to promote rapid formation of functional endothelium are required to maintain blood fluidity and regulate smooth muscle cell proliferation in synthetic vascular conduits. In this work, we explored the biofunctionalization of silk biomaterials ... ...

    Abstract Strategies to promote rapid formation of functional endothelium are required to maintain blood fluidity and regulate smooth muscle cell proliferation in synthetic vascular conduits. In this work, we explored the biofunctionalization of silk biomaterials with recombinantly expressed domain V of human perlecan (rDV) to promote endothelial cell interactions and the formation of functional endothelium. Perlecan is essential in vascular development and homeostasis and rDV has been shown to uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions, both key contributors of vascular graft failure. rDV was covalently immobilized on silk using plasma immersion ion implantation (PIII), a simple one-step surface treatment process which enables strong immobilization in the absence of chemical cross-linkers. rDV immobilization on surface-modified silk was assessed for amount, orientation, and bio-functionality in terms of endothelial cell interactions and functional endothelial layer formation. rDV immobilized on PIII-treated silk (rDV-PIII-silk) supported rapid endothelial cell adhesion, spreading, and proliferation to form functional endothelium, as evidenced by the expression of vinculin and VE-cadherin markers. Taken together, the results provide evidence for the potential of rDV-PIII-silk as a biomimetic vascular graft material.
    MeSH term(s) Humans ; Silk/chemistry ; Biocompatible Materials ; Immersion ; Cell Adhesion ; Blood Vessel Prosthesis ; Extracellular Matrix Proteins ; Endothelium
    Chemical Substances Silk ; Biocompatible Materials ; perlecan (143972-95-6) ; Extracellular Matrix Proteins
    Language English
    Publishing date 2023-03-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2099989-6
    ISSN 1552-4965 ; 1549-3296 ; 0021-9304
    ISSN (online) 1552-4965
    ISSN 1549-3296 ; 0021-9304
    DOI 10.1002/jbm.a.37525
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    Zs.A 6195: Show issues Location:
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  4. Article ; Online: Editorial

    Shuji Mizumoto / Jessica C. F. Kwok / John M. Whitelock / Fuchuan Li / Roberto Perris

    Frontiers in Cell and Developmental Biology, Vol

    Roles of Chondroitin Sulfate and Dermatan Sulfate as Regulators for Cell and Tissue Development

    2022  Volume 10

    Keywords chondroitin sulfate ; dermatan sulfate ; proteoglycan ; cell signal ; stem cell ; tissue morphogenesis ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: ROS-Mediated Anti-Angiogenic Activity of Cerium Oxide Nanoparticles in Melanoma Cells.

    Yong, Joel M / Fu, Lu / Tang, Fengying / Yu, Peimin / Kuchel, Rhiannon P / Whitelock, John M / Lord, Megan S

    ACS biomaterials science & engineering

    2022  Volume 8, Issue 2, Page(s) 512–525

    Abstract: Angiogenesis plays a key role in cancer progression, including transition to the metastatic ... ...

    Abstract Angiogenesis plays a key role in cancer progression, including transition to the metastatic phase
    MeSH term(s) Cerium/pharmacology ; Humans ; Melanoma/drug therapy ; Nanoparticles ; Reactive Oxygen Species/metabolism
    Chemical Substances Reactive Oxygen Species ; Cerium (30K4522N6T) ; ceric oxide (619G5K328Y)
    Language English
    Publishing date 2022-01-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2373-9878
    ISSN (online) 2373-9878
    DOI 10.1021/acsbiomaterials.1c01268
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  6. Article ; Online: The Inter-α-Trypsin Inhibitor Family: Versatile Molecules in Biology and Pathology.

    Lord, Megan S / Melrose, James / Day, Anthony J / Whitelock, John M

    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society

    2020  Volume 68, Issue 12, Page(s) 907–927

    Abstract: Inter-α-trypsin inhibitor (IαI) family members are ancient and unique molecules that have evolved over several hundred million years of vertebrate evolution. IαI is a complex containing the proteoglycan bikunin to which heavy chain proteins are ... ...

    Abstract Inter-α-trypsin inhibitor (IαI) family members are ancient and unique molecules that have evolved over several hundred million years of vertebrate evolution. IαI is a complex containing the proteoglycan bikunin to which heavy chain proteins are covalently attached to the chondroitin sulfate chain. Besides its matrix protective activity through protease inhibitory action, IαI family members interact with extracellular matrix molecules and most notably hyaluronan, inhibit complement, and provide cell regulatory functions. Recent evidence for the diverse roles of the IαI family in both biology and pathology is reviewed and gives insight into their pivotal roles in tissue homeostasis. In addition, the clinical uses of these molecules are explored, such as in the treatment of inflammatory conditions including sepsis and Kawasaki disease, which has recently been associated with severe acute respiratory syndrome coronavirus 2 infection in children.
    MeSH term(s) Alpha-Globulins/analysis ; Alpha-Globulins/metabolism ; Animals ; Arthritis/metabolism ; Arthritis/pathology ; Asthma/metabolism ; Asthma/pathology ; Extracellular Matrix/metabolism ; Extracellular Matrix/pathology ; Fibrosis ; Humans ; Hyaluronic Acid/metabolism ; Inflammation/metabolism ; Inflammation/pathology ; Sepsis/metabolism ; Sepsis/pathology
    Chemical Substances Alpha-Globulins ; inter-alpha-inhibitor (39346-44-6) ; Hyaluronic Acid (9004-61-9)
    Keywords covid19
    Language English
    Publishing date 2020-07-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 218208-7
    ISSN 1551-5044 ; 0022-1554
    ISSN (online) 1551-5044
    ISSN 0022-1554
    DOI 10.1369/0022155420940067
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    Uc I Zs.321: Show issues Location:
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  7. Article ; Online: Targeted Delivery and Redox Activity of Folic Acid-Functionalized Nanoceria in Tumor Cells.

    Vassie, James A / Whitelock, John M / Lord, Megan S

    Molecular pharmaceutics

    2018  Volume 15, Issue 3, Page(s) 994–1004

    Abstract: Cerium oxide nanoparticles (nanoceria) are promising catalytic nanomaterials that are widely reported to modulate intracellular reactive oxygen species (ROS). In this study, nanoceria were synthesized by flame spray pyrolysis and functionalized with a ... ...

    Abstract Cerium oxide nanoparticles (nanoceria) are promising catalytic nanomaterials that are widely reported to modulate intracellular reactive oxygen species (ROS). In this study, nanoceria were synthesized by flame spray pyrolysis and functionalized with a cell-targeting ligand, folic acid (FA). The surface functionalization of nanoceria was stable, and FA enhanced the uptake of nanoceria via folate receptors. Internalized nanoceria and FA-nanoceria were localized predominantly in the cytoplasm. FA-nanoceria modulated intracellular ROS to a greater extent than the nanoceria in colon carcinoma cells, but induced ROS in ovarian cancer cells, likely due to their enhanced uptake. Together these data demonstrated that the functionalization of nanoceria with FA modulated their endocytosis and redox activity, and they may find application in the delivery of anticancer drugs in the future.
    MeSH term(s) Antioxidants/administration & dosage ; Antioxidants/chemistry ; Cell Line, Tumor ; Cerium/administration & dosage ; Cerium/chemistry ; Endocytosis/drug effects ; Female ; Folate Receptor 1/metabolism ; Folic Acid/chemistry ; Humans ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Oxidation-Reduction/drug effects ; Reactive Oxygen Species/metabolism
    Chemical Substances Antioxidants ; Folate Receptor 1 ; Reactive Oxygen Species ; Cerium (30K4522N6T) ; ceric oxide (619G5K328Y) ; Folic Acid (935E97BOY8)
    Language English
    Publishing date 2018-02-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.7b00920
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    Zs.A 6250: Show issues Location:
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  8. Article ; Online: Biocatalytic Buoyancy-Driven Nanobots for Autonomous Cell Recognition and Enrichment.

    Guo, Ziyi / Zhuang, Chenchen / Song, Yihang / Yong, Joel / Li, Yi / Guo, Zhong / Kong, Biao / Whitelock, John M / Wang, Joseph / Liang, Kang

    Nano-micro letters

    2023  Volume 15, Issue 1, Page(s) 236

    Abstract: Autonomously self-propelled nanoswimmers represent the next-generation nano-devices for bio- and environmental technology. However, current nanoswimmers generate limited energy output and can only move in short distances and duration, thus are struggling ...

    Abstract Autonomously self-propelled nanoswimmers represent the next-generation nano-devices for bio- and environmental technology. However, current nanoswimmers generate limited energy output and can only move in short distances and duration, thus are struggling to be applied in practical challenges, such as living cell transportation. Here, we describe the construction of biodegradable metal-organic framework based nanobots with chemically driven buoyancy to achieve highly efficient, long-distance, directional vertical motion to "find-and-fetch" target cells. Nanobots surface-functionalized with antibodies against the cell surface marker carcinoembryonic antigen are exploited to impart the nanobots with specific cell targeting capacity to recognize and separate cancer cells. We demonstrate that the self-propelled motility of the nanobots can sufficiently transport the recognized cells autonomously, and the separated cells can be easily collected with a customized glass column, and finally regain their full metabolic potential after the separation. The utilization of nanobots with easy synthetic pathway shows considerable promise in cell recognition, separation, and enrichment.
    Language English
    Publishing date 2023-10-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2642093-4
    ISSN 2150-5551 ; 2150-5551
    ISSN (online) 2150-5551
    ISSN 2150-5551
    DOI 10.1007/s40820-023-01207-1
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  9. Article ; Online: Optimization of bioengineered heparin/heparan sulfate production for therapeutic applications.

    Lord, Megan S / Jung, MoonSun / Whitelock, John M

    Bioengineered

    2017  Volume 8, Issue 5, Page(s) 661–664

    Abstract: Heparin has been used clinically as an anti-coagulant for more than 100 y and the major source of this therapeutic is still animal tissues. Contamination issues in some batches of heparin over 10 y ago have highlighted the need to develop alternative ... ...

    Abstract Heparin has been used clinically as an anti-coagulant for more than 100 y and the major source of this therapeutic is still animal tissues. Contamination issues in some batches of heparin over 10 y ago have highlighted the need to develop alternative methods of production of this essential drug.
    MeSH term(s) Genetic Enhancement/methods ; Glucose/metabolism ; HEK293 Cells ; Heparin/biosynthesis ; Heparin/genetics ; Heparin/isolation & purification ; Heparitin Sulfate/biosynthesis ; Heparitin Sulfate/genetics ; Heparitin Sulfate/isolation & purification ; Humans ; Proteoglycans/genetics ; Proteoglycans/metabolism ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism
    Chemical Substances Proteoglycans ; Recombinant Proteins ; Vesicular Transport Proteins ; serglycin ; Heparin (9005-49-6) ; Heparitin Sulfate (9050-30-0) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2017-09-03
    Publishing country United States
    Document type Journal Article
    ISSN 2165-5987
    ISSN (online) 2165-5987
    DOI 10.1080/21655979.2017.1301328
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  10. Article ; Online: Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates Produced in Different Bioreactors.

    Kim, Ha Na / Whitelock, John M / Lord, Megan S

    Molecules (Basel, Switzerland)

    2017  Volume 22, Issue 5

    Abstract: Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/ ... ...

    Abstract Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains. The serglycin produced in tissue culture flasks was effective in binding and signaling fibroblast growth factor 2, indicating the utility of this molecule in drug delivery and regenerative medicine applications in addition to its well-known anticoagulant activity.
    MeSH term(s) Animals ; Bioreactors ; Fibroblast Growth Factor 2/metabolism ; Heparin/chemistry ; Heparitin Sulfate/chemistry ; Humans ; Proteoglycans/chemistry ; Structure-Activity Relationship ; Vesicular Transport Proteins/chemistry
    Chemical Substances Proteoglycans ; Vesicular Transport Proteins ; serglycin ; Fibroblast Growth Factor 2 (103107-01-3) ; Heparin (9005-49-6) ; Heparitin Sulfate (9050-30-0)
    Language English
    Publishing date 2017-05-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules22050806
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