Valerie Barron

Publications (35) View all

• Article: Liposomal surface coatings of metal stents for efficient non-viral gene delivery to the injured vasculature.

  Sandra Ganly, Sean O Hynes, Faisal Sharif, Ahmed Aied, Valerie Barron, Karl McCullagh, Jill McMahon, Peter McHugh, Jim Crowley, Wenxin Wang, Timothy O'Brien, Udo Greiser
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  ABSTRACT: Despite the widespread use of drug eluting stents (DES), in-stent restenosis (ISR), delayed arterial healing and thrombosis remain important clinical complications. Gene-eluting stents (GES) represent a potential strategy for the prevention of ISR by delivering a therapeutic gene via a vector from the stent surface to the vessel wall. To this end, a model in vitro system was established to examine whether cationic liposomes could be used for gene delivery to human artery cells. Three different formulations were compared (DOTMA/DOPE, DDAB/DOPE or DDAB/POPC/Chol) to examine the effects of different cationic and neutral lipids on the transfection efficiency of lipoplex-coatings of metal surfaces. Upon completion of the characterization and optimization of the materials for gene delivery in vitro, these coatings were examined on a range of stents and deployed in a rabbit iliac artery injury model in vivo. Maximal transfection efficiencies for all coatings were observed on day 28, followed by declining, but persisting gene expression 42days after stent placement, thereby, presenting liposomal coatings for gene eluting stents as treatment options for clinical complications associated with stenting procedures.
  Journal of Controlled Release 02/2013; 167(2):109-119. · 5.73 Impact Factor
• Article: Enhancing the Mesenchymal Stem Cell Therapeutic Response: Cell Localization and Support for Cartilage Repair.

  Sarah E Bulman, Valerie Barron, Cynthia M Coleman, Frank Barry
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  ABSTRACT: Articular cartilage is a complex, multilayered biological composite material, comprised of chondrocytes encapsulated in a water-based glycosaminoglycan matrix reinforced with collagen fibers. Once damaged by osteoarthritis or traumatic injury, this aneural, avascular tissue has little self-repair capacity. Over the last 20 years, cell therapies and tissue-engineering strategies have shown significant promise for the repair or regeneration of damaged cartilage. In particular, mesenchymal stem cells (MSCs) have great potential owing to their ability to create a reparative environment. Despite the fact that there have been great strides in the design and development of three-dimensional scaffolds, there is an upper limit to the number of viable cells that can be delivered using current approaches. To this end, this review examines current strategies for optimizing MSC localization, evaluates their limitations, and looks to other technologies to devise a combinatorial strategy for the creation of an MSC-seeded composite structure that addresses both the mechanical and biological property requirements for enhanced cartilage repair.
  Tissue Engineering Part B Reviews 08/2012; · 4.64 Impact Factor
• Source

  Available from: Werner J Blau

  Article: The electrical stimulation of carbon nanotubes to provide a cardiomimetic cue to MSCs.

  Emma Mooney, Joseph N Mackle, David J-P Blond, Eoin O'Cearbhaill, Georgina Shaw, Werner J Blau, Frank P Barry, Valerie Barron, J Mary Murphy
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  ABSTRACT: Once damaged, cardiac muscle has little intrinsic repair capability due to the poor regeneration potential of remaining cardiomyocytes. One method of overcoming this issue is to deliver functional cells to the injured myocardium to promote repair. To address this limitation we sought to test the hypothesis that electroactive carbon nanotubes (CNT) could be employed to direct mesenchymal stem cell (MSC) differentiation towards a cardiomyocyte lineage. Using a two-pronged approach, MSCs exposed to medium containing CNT and MSCs seeded on CNT based polylactic acid scaffolds were electrically stimulated in an electrophysiological bioreactor. After electrical stimulation the cells reoriented perpendicular to the direction of the current and adopted an elongated morphology. Using qPCR, an upregulation in a range of cardiac markers was detected, the greatest of which was observed for cardiac myosin heavy chain (CMHC), where a 40-fold increase was observed for the electrically stimulated cells after 14 days, and a 12-fold increase was observed for the electrically stimulated cells seeded on the PLA scaffolds after 10 days. Differentiation towards a cardioprogenitor cell was more evident from the western blot analysis, where upregulation of Nkx2.5, GATA-4, cardiac troponin t (CTT) and connexin43 (C43) was seen to occur. This was echoed in immunofluorescent staining, where increased levels of CTT, CMHC and C43 protein expression were observed after electrical stimulation for both cells and cell-seeded scaffolds. More interestingly, there was evidence of increased cross talk between the cells as shown by the pattern of C43 staining after electrical stimulation. These results establish a paradigm for nanoscale biomimetic cues that can be readily translated to other electroactive tissue repair applications.
  Biomaterials 06/2012; 33(26):6132-9. · 7.40 Impact Factor
• Article: Fabrication, mechanical and in vivo performance of polycaprolactone/tricalcium phosphate composite scaffolds.

  Stefan Lohfeld, Senan Cahill, Valerie Barron, Peter McHugh, Lutz Dürselen, Ludwika Kreja, Christine Bausewein, Anita Ignatius
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  ABSTRACT: This paper explores the use of selective laser sintering (SLS) for the generation of bone tissue engineering scaffolds from polycaprolactone (PCL) and PCL/tricalcium phosphate (TCP). Different scaffold designs are generated, and assessed from the point of view of manufacturability, porosity and mechanical performance. Large scaffold specimens are produced, with a preferred design, and are assessed through an in vivo study of the critical size bone defect in sheep tibia with subsequent microscopic, histological and mechanical evaluation. Further explorations are performed to generate scaffolds with increasing TCP content. Scaffold fabrication from PCL and PCL/TCP mixtures with up to 50 mass% TCP is shown to be possible. With increasing macroporosity the stiffness of the scaffolds is seen to drop; however, the stiffness can be increased by minor geometrical changes, such as the addition of a cage around the scaffold. In the animal study the selected scaffold for implantation did not perform as well as the TCP control in terms of new bone formation and the resulting mechanical performance of the defect area. A possible cause for this is presented.
  Acta biomaterialia 05/2012; 8(9):3446-56. · 3.98 Impact Factor
• Article: Behavior of Human Mesenchymal Stem Cells in Fibrin-Based Vascular Tissue Engineering Constructs

  Eoin D. O’Cearbhaill, Mary Murphy, Frank Barry, Peter E. McHugh, Valerie Barron
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  ABSTRACT: A limitation of current tissue engineering vascular graft technology is the provision of an expandable, autologous cell source. By harnessing the multipotency of mesenchymal stem cells (MSC), it is hoped that functional vascular cells can be produced. To date, a range of 2D and 3D environments have been investigated for the manipulation of MSC differentiation pathways. To this end, this study aims to test the hypothesis that MSC seeded in various fibrin gel environments will exhibit evidence of a smooth muscle cell (SMC) phenotype. Initially, a range of cell-seeding densities were screened for 2D and 3D fibrin constructs, where it was observed that a seeding densities of 500,000cells/mL facilitated gel compaction without degradation or loss in cell viability. Additionally, positive expression of CD49, CD73, CD105 markers and negative expression of hemopoietic stem cell-associated CD34 and CD45 indicated that MSC phenotype was retained within the fibrin gel. Nonetheless, a decrease in the gene expression of α-smooth cell actin and calponin was observed for MSC cultured in static 3D fibrin gels. Although a slight recovery was observed after 24h mechanical stimulation, the fold-change remained significantly lower than that observed for cells cultured on 2D tissue culture plastic. While MSC differentiation toward a SMC appears possible in both 2D and 3D environments, scaffold architecture and mechanical stimulation undoubtedly play an important role in the creation of a functional SMC phenotype. KeywordsMesenchymal stem cell-Fibrin scaffold-2D and 3D environments-Biomechanical stimulation-Hoop strain-Differentiation-Smooth muscle cell
  Annals of Biomedical Engineering 04/2012; 38(3):649-657. · 2.37 Impact Factor