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  1. Article ; Online: Perianal fistulae in Crohn's Disease: current and future approaches to treatment.

    Keshaw, Hussila / Foong, Keen S / Forbes, Alastair / Day, Richard M

    Inflammatory bowel diseases

    2009  Volume 16, Issue 5, Page(s) 870–880

    Abstract: affecting sphincter integrity and continence. Traditional surgical and medical approaches are not without their limitations and may result in either comorbidity, such as fecal incontinence, or incomplete healing of the fistulae. Over the last 2 decades ...

    Abstract : affecting sphincter integrity and continence. Traditional surgical and medical approaches are not without their limitations and may result in either comorbidity, such as fecal incontinence, or incomplete healing of the fistulae. Over the last 2 decades these limitations have led to a paradigm shift toward the use of biomaterials, and more recently cell-based therapies, which have met with variable degrees of success. This review discusses the traditional and current methods of treatment, as well as emerging and possible alternative approaches that may improve fistula healing.
    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Crohn Disease/complications ; Crohn Disease/therapy ; Humans ; Immunosuppressive Agents/therapeutic use ; Rectal Fistula/etiology ; Rectal Fistula/therapy
    Chemical Substances Anti-Bacterial Agents ; Immunosuppressive Agents
    Language English
    Publishing date 2009-08-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1340971-2
    ISSN 1536-4844 ; 1078-0998
    ISSN (online) 1536-4844
    ISSN 1078-0998
    DOI 10.1002/ibd.21137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Release of angiogenic growth factors from cells encapsulated in alginate beads with bioactive glass.

    Keshaw, Hussila / Forbes, Alastair / Day, Richard M

    Biomaterials

    2005  Volume 26, Issue 19, Page(s) 4171–4179

    Abstract: Attempts to stimulate therapeutic angiogenesis using gene therapy or delivery of recombinant growth factors, such as vascular endothelial growth factor (VEGF), have failed to demonstrate unequivocal efficacy in human trials. Bioactive glass stimulates ... ...

    Abstract Attempts to stimulate therapeutic angiogenesis using gene therapy or delivery of recombinant growth factors, such as vascular endothelial growth factor (VEGF), have failed to demonstrate unequivocal efficacy in human trials. Bioactive glass stimulates fibroblasts to secrete significantly increased amounts of angiogenic growth factors and therefore has a number of potential applications in therapeutic angiogenesis. The aim of this study was to assess whether it is possible to encapsulate specific quantities of bioactive glass and fibroblasts into alginate beads, which will secrete growth factors capable of stimulating angiogenesis. Human fibroblasts (CCD-18Co) were encapsulated in alginate beads with specific quantities of 45S5 bioactive glass and incubated in culture medium (0-17 days). The conditioned medium was collected and assayed for VEGF or used to assess its ability to stimulate angiogenesis by measuring the proliferation of human dermal microvascular endothelial cells. At 17 days the beads were lysed and the amount of VEGF retained by the beads measured. Fibroblasts encapsulated in alginate beads containing 0.01% and 0.1% (w/v) 45S5 bioactive glass particles secreted increased quantities of VEGF compared with cells encapsulated with 0% or 1% (w/v) 45S5 bioactive glass particles. Lysed alginate beads containing 0.01% and 0.1% (w/v) 45S5 bioactive glass contained significantly more VEGF (p<0.01) compared with beads containing no glass particles. Endothelial cell proliferation was significantly increased (p<0.01) by conditioned medium collected from alginate beads containing 0.1% (w/v) 45S5 bioactive glass particles. The results of this study demonstrate that bioactive glass and fibroblasts can be successfully incorporated into alginate beads for use in delivering angiogenic growth factors. With further optimization, this technique offers a novel delivery device for stimulating therapeutic angiogenesis.
    MeSH term(s) Alginates/chemistry ; Bioreactors ; Cell Culture Techniques/methods ; Cell Line ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Ceramics ; Drug Delivery Systems/methods ; Drug Implants ; Endothelial Cells/cytology ; Endothelial Cells/drug effects ; Endothelial Cells/physiology ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/secretion ; Glass/chemistry ; Glucuronic Acid/chemistry ; Hexuronic Acids/chemistry ; Humans ; Microspheres ; Neovascularization, Physiologic/drug effects ; Neovascularization, Physiologic/physiology ; Tissue Engineering/methods ; Vascular Endothelial Growth Factor A/pharmacology ; Vascular Endothelial Growth Factor A/secretion
    Chemical Substances Alginates ; Drug Implants ; Hexuronic Acids ; Vascular Endothelial Growth Factor A ; bioactive glass 45S5 ; Glucuronic Acid (8A5D83Q4RW) ; alginic acid (8C3Z4148WZ)
    Language English
    Publishing date 2005-07
    Publishing country Netherlands
    Document type Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2004.10.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Assessment of polymer/bioactive glass-composite microporous spheres for tissue regeneration applications.

    Keshaw, Hussila / Georgiou, George / Blaker, Jonny J / Forbes, Alastair / Knowles, Jonathan C / Day, Richard M

    Tissue engineering. Part A

    2008  Volume 15, Issue 7, Page(s) 1451–1461

    Abstract: Conformable scaffold materials capable of rapid vascularization and tissue infiltration would be of value in the therapy of inaccessible wounds. Microporous spheres of poly(D,L-lactide-co-glycolide) (PLGA) containing bioactive glass (BG) were prepared ... ...

    Abstract Conformable scaffold materials capable of rapid vascularization and tissue infiltration would be of value in the therapy of inaccessible wounds. Microporous spheres of poly(D,L-lactide-co-glycolide) (PLGA) containing bioactive glass (BG) were prepared using a thermally induced phase separation (TIPS) technique, and the bioactivity, in vitro degradation, and tissue integration of the microporous spheres were assessed. Microporous spheres containing 10% (w/w) BG stimulated a significant increase in vascular endothelial growth factor secretion from myofibroblasts consistently over a 10-day period (p < 0.01) compared with the neat PLGA microporous spheres. The microporous spheres degraded steadily in vitro over a 16-week period, with the neat PLGA microporous spheres retaining 82% of their original weight and microporous spheres containing 10% (w/w) BG retaining 77%. Both types of microporous spheres followed a similar pattern of size reduction throughout the degradation study, resulting in a 23% and 20% reduction after 16 weeks for the neat PLGA microporous spheres and PLGA microporous spheres containing 10% (w/w) BG, respectively (p < 0.01). After in vivo implantation into a subcutaneous wound model, the TIPS microporous spheres became rapidly integrated (interspherically and intraspherically) with host tissue, including vascularization of voids inside the microporous sphere. The unique properties of TIPS microporous spheres make them ideally suited for regenerative medicine applications where tissue augmentation is required.
    MeSH term(s) Animals ; Cell Survival ; Cells, Cultured ; Compressive Strength ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Glass/chemistry ; Humans ; Implants, Experimental ; Lactic Acid/chemistry ; Materials Testing/methods ; Microscopy, Electron, Scanning ; Microspheres ; Polyglycolic Acid/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer ; Porosity ; Rats ; Regeneration ; Subcutaneous Tissue/metabolism ; Tissue Engineering/methods ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Vascular Endothelial Growth Factor A ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS) ; Polyglycolic Acid (26009-03-0) ; Lactic Acid (33X04XA5AT)
    Language English
    Publishing date 2008-12-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2420582-5
    ISSN 1937-335X ; 1937-3341
    ISSN (online) 1937-335X
    ISSN 1937-3341
    DOI 10.1089/ten.tea.2008.0203
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Microporous collagen spheres produced via thermally induced phase separation for tissue regeneration.

    Keshaw, Hussila / Thapar, Nikhil / Burns, Alan J / Mordan, Nicola / Knowles, Jonathan C / Forbes, Alastair / Day, Richard M

    Acta biomaterialia

    2009  Volume 6, Issue 3, Page(s) 1158–1166

    Abstract: Collagen is an abundant protein found in the extracellular matrix of many tissues. Due to its biocompatibility, it is a potentially ideal biomaterial for many tissue engineering applications. However, harvested collagen often requires restructuring into ... ...

    Abstract Collagen is an abundant protein found in the extracellular matrix of many tissues. Due to its biocompatibility, it is a potentially ideal biomaterial for many tissue engineering applications. However, harvested collagen often requires restructuring into a three-dimensional matrix to facilitate applications such as implantation into poorly accessible tissue cavities. The aim of the current study was to produce a conformable collagen-based scaffold material capable of supporting tissue regeneration for use in wound repair applications. Microporous collagen spheres were prepared using a thermally induced phase separation (TIPS) technique and their biocompatibility was assessed. The collagen spheres were successfully cross-linked with glutaraldehyde vapour, rendering them mechanically more stable. When cultured with myofibroblasts the collagen spheres stimulated a prolonged significant increase in secretion of the angiogenic growth factor, vascular endothelial growth factor (VEGF), compared with cells alone. Control polycaprolactone (PCL) spheres failed to stimulate a similar prolonged increase in VEGF secretion. An enhanced angiogenic effect was also seen in vivo using the chick embryo chorioallantoic membrane assay, where a significant increase in the number of blood vessels converging towards collagen spheres was observed compared with control PCL spheres. The results from this study indicate that microporous collagen spheres produced using TIPS are biologically active and could offer a novel conformable scaffold for tissue regeneration in poorly accessible wounds.
    MeSH term(s) Biocompatible Materials/chemistry ; Cell Proliferation ; Cells, Cultured ; Collagen/chemistry ; Guided Tissue Regeneration/methods ; Humans ; Materials Testing ; Microspheres ; Myoblasts/cytology ; Myoblasts/physiology ; Phase Transition ; Polyesters/chemistry ; Porosity ; Temperature
    Chemical Substances Biocompatible Materials ; Polyesters ; polycaprolactone (24980-41-4) ; Collagen (9007-34-5)
    Language English
    Publishing date 2009-09-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2009.08.044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice.

    Xu, Aimin / Wang, Yu / Keshaw, Hussila / Xu, Lance Yi / Lam, Karen S L / Cooper, Garth J S

    The Journal of clinical investigation

    2003  Volume 112, Issue 1, Page(s) 91–100

    Abstract: Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained ... ...

    Abstract Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.
    MeSH term(s) Adiponectin ; Alanine Transaminase/blood ; Animals ; Fatty Acids/metabolism ; Fatty Liver/drug therapy ; Fatty Liver/metabolism ; Fatty Liver, Alcoholic/drug therapy ; Fatty Liver, Alcoholic/metabolism ; Intercellular Signaling Peptides and Proteins ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity, Morbid/blood ; Oxidation-Reduction ; Proteins/analysis ; Proteins/therapeutic use ; Recombinant Proteins/therapeutic use ; Tumor Necrosis Factor-alpha/biosynthesis
    Chemical Substances Adiponectin ; Fatty Acids ; Intercellular Signaling Peptides and Proteins ; Proteins ; Recombinant Proteins ; Tumor Necrosis Factor-alpha ; Alanine Transaminase (EC 2.6.1.2)
    Language English
    Publishing date 2003-06-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI17797
    Database MEDical Literature Analysis and Retrieval System OnLINE

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