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Sedgefield, United Kingdom

Cooke M.J.,Durham University | Zahir T.,University of Toronto | Phillips S.R.,United Technologies | Shah D.S.H.,United Technologies | And 6 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2010

The interaction between cells and the extracellular matrix (ECM) is essential during development. To elucidate the function of ECM proteins on cell differentiation, we developed biomimetic surfaces that display specific ECM peptide motifs in a controlled manner. Presentation of ECM domains for collagen, fibronectin, and laminin influenced the formation of neurites by differentiating PC12 cells. The effect of these peptide sequences was also tested on the development of adult neural stem/progenitor cells. In this system, collagen I and fibronectin induced the formation of beta-III-tubulin positive cells, whereas collagen IV reduced such differentiation. Biomimetic surfaces composed of multiple peptide types enabled the combinatorial effects of various ECM motifs to be studied. Surfaces displaying combined motifs were often predictable as a result of the synergistic effects of ECM peptides studied in isolation. For example, the additive effects of fibronectin and laminin resulted in greater expression of beta-III-tubulin positive cells, whereas the negative effect of the collagen IV domain was canceled out by coexpression of collagen I. However, simultaneous expression of certain ECM domains was less predictable. These data highlight the complexity of the cellular response to combined ECM signals and the need to study the function of ECM domains individually and in combination. © 2009 Wiley Periodicals, Inc.


Schutte M.,LCG Group | Fox B.,LCG Group | Baradez M.-O.,LCG Group | Devonshire A.,LCG Group | And 5 more authors.
Assay and Drug Development Technologies | Year: 2011

The in vitro evaluation of hepatotoxicity is an essential stage in the research and development of new pharmaceuticals as the liver is one of the most commonly impacted organs during preclinical toxicity studies. Fresh primary hepatocytes in monolayer culture are the most commonly used in vitro model of the liver but often exhibit limited viability and/or reduction or loss of important liver-specific functions. These limitations could potentially be overcome using three-dimensional (3D) culture systems, but their experimental nature and limited use in liver toxicity screening and drug metabolism has impaired their uptake into commercial screening programs. In this study we use a commercially available polystyrene scaffold developed for routine 3D cell culture to maintain primary rat hepatocytes for use in metabolism and toxicity studies over 72 h. We show that primary hepatocytes retain their natural cuboidal morphology with significantly higher viability (>74%) than cells grown in monolayer culture (maximum of 57%). Hepatocytes in the 3D scaffolds exhibit differential expression of genes associated with phase I, II, and III drug metabolism under basal conditions compared with monolayer culture and can be induced to stably express significantly higher levels of the cytochrome-P450 enzymes 1A2, 2B1, and 3A2 over 48 h. In toxicity studies the hepatocytes in the 3D scaffolds also show increased sensitivity to the model toxicant acetaminophen. These improvements over monolayer culture and the availability of this new easy to use 3D scaffold system could facilitate the uptake of 3D technologies into routine drug screening programs. © Copyright 2011, Mary Ann Liebert, Inc.


Caldwell S.,Durham University | Johnson D.W.,Durham University | Didsbury M.P.,Durham University | Murray B.A.,Durham University | And 4 more authors.
Soft Matter | Year: 2012

Emulsion templating has been used to prepare highly porous polyHIPE materials by thiol-ene photoinitiated network formation. Commercially available multifunctional thiols and acrylates were formulated into water-in-oil high internal phase emulsions (HIPEs) using an appropriate surfactant, and the HIPEs were photo-cured. The temperature of the HIPE aqueous phase was found to influence the morphology of the resulting materials. In agreement with previous work, a higher aqueous phase temperature (80 °C) gave rise to a larger mean void and interconnect diameter. The influence of temperature on morphology was found to be reduced at higher porosity, but still significant. The Young's modulus of the porous materials was shown to be related to the functionality of the acrylate comonomer used. A mixture of penta- and hexa-acrylate gave rise to a 100-fold increase in modulus, compared to an analogous tri-functional acrylate. The materials could be functionalised conveniently by addition of mono-acrylates or thiols to the organic phase of the precursor HIPE. Degradation was observed to occur at a rate depending on the degradation conditions. Under cell culture conditions at 37 °C, 19% mass loss occurred over 15 weeks. The scaffolds were found to be capable of supporting the growth of keratinocytic cells (HaCaTs) over 11 days in culture. Some penetrative in-growth of the cells into the scaffold was observed. © The Royal Society of Chemistry 2012.


Trademark
ReInnervate | Date: 2012-02-21

Biological preparations for use in the induction of cell differentiation in cell cultures and synthetic small molecules for use in the induction of in-vitro cell differentiation, other than medical; cell growth media for growing cells for use in scientific research; media for cell culture for use, namely, in non-medical research and biotechnological laboratories; chemical preparations for biotechnological purposes, namely, for the induction of cell differentiation, in particular stem cell differentiation; reagents for use in scientific apparatus for chemical or biological analysis; chemical preparations, agents and reagents for use in cellular research; biochemicals, namely, monoclonal antibodies other than for medical or veterinary purposes; biochemicals, namely, antibodies for diagnostic, laboratory, industrial or scientific use other than medical; biochemical products containing antibodies for use in scientific research. Pharmaceutical preparations for the treatment of skin and neuro-degenerative diseases; medical biological reagents for use in molecular biology; medical diagnostic reagents; medical diagnostic reagents for in vitro laboratory tests; chemical reagents for medical and veterinary purposes; chemical preparations, agents and reagents for medical and veterinary use, namely, in the differentiation of cell types; biological preparations for the treatment of skin and neuro-degenerative diseases; cell growth media for growing cells for medical or clinical use; diagnostic agents, preparations and substances for medical purposes, namely, for use in binding or detecting antibodies, and in the development of antibodies. Cell culture apparatus and instruments for laboratory or research medical use; laboratory apparatus, namely, cell culture vessels, multiwell plates, petri dishes, cell culture well inserts, cell factories, cell culture flasks and bioreactors for use in the separation of antibodies; reaction units, namely, cell based assays, routine cell cultures, cell passaging and perfusion cell culture systems containing chemical or biological reagents; cell culture scaffolds, namely, microspun fibres and microporous polystyrene substrates coated with extra-cellular matrices; deep well plates, namely, deep reservoir petri dishes with and without well insert cradles used in laboratory research. Batch biological and chemical treatment services of materials; batch biological and chemical material treatment involving cell culture processes and the differentiation of cell types; treatment of human, animal and plant cells, bacteria and antibody materials by culturing such cells in three dimensions; material treatment involving three dimensional cell culture processes and in-vitro stem cell differentiation. Education services, namely, provision of training, arranging and conducting of seminars and workshops all in the fields of biology, biotechnology, cell culture, cell biology, toxicity and safety testing, tissue and disease modelling and drug efficacy; on-line non-downloadable electronic publications, namely, bulletins and journal articles in the fields of biology, biotechnology, cell culture, cell biology, toxicity and safety testing, tissue and disease modelling and drug efficacy. Scientific research and design services in the field of three dimensional cell culture and analytical processes; industrial analysis and research services in the field of cell culture, cell biology, toxicity and safety testing, tissue and disease modelling and drug efficacy; laboratory services, namely, analysis and research in the field of cell and tissue cultures and their treatment; biotechnology research; laboratory services relating to the production of antibodies; growing cell cultures for research purposes; testing pharmaceutical, medical and biological agents for others; consultancy relating to biotechnology.


Trademark
ReInnervate | Date: 2011-10-04

Cell culture apparatus and instruments for laboratory or research medical use; laboratory apparatus, namely, cell culture laboratory vessels, plates having multi-well arrays, petri dishes, cell culture well inserts, laboratory glassware, cell factories, cell culture flasks and bioreactors for use in the separation of antibodies; reaction units for cell based assay research, routine cell cultures, cell passaging research and perfusion cell culture systems research containing chemical or biological reagents; cell culture scaffolds, namely, microspun fibres and microporous polystyrene substrates coated with extra-cellular matrices for use in three-dimensional cell culturing; deep well plates, namely, deep reservoir petri dishes with and without well insert cradles used in laboratory research. Treatment of human, animal and plant cells, bacteria and antibody materials by culturing such cells in three dimensions; material treatment involving three dimensional cell culture processes and in-vitro stem cell differentiation. Scientific research and design services in the field of three dimensional cell culture and analytical processes; industrial analysis and research services in the field of cell culture, cell biology, toxicity and safety testing, tissue and disease modelling and drug efficacy; laboratory services, namely, analysis and research in the field of cell and tissue cultures and their treatment; biotechnology research; laboratory services relating to the production of antibodies; growing cell cultures for research purposes; testing pharmaceutical, medical and biological agents for others; consultancy relating to biotechnology.

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