title: Design and evaluation of a novel subatmospheric pressure bioreactor for the preconditioning of tissue-engineered vascular constructs.
abstract: OBJECTIVE
  The pre-conditioning of tissue-engineered vascular scaffolds with mechanical stimuli is being recognised as an essential step in producing a functional vascular construct. In this study we design and evaluate a novel bioreactor, which exerts a mechanical strain on developing vascular scaffolds via subatmospheric pressure.
  
  
  METHODS
  We design and construct a bioreactor, which exerts subatmospheric pressure via a vacuum assisted closure unit. Vascular scaffolds seeded with human umbilical endothelial cells were evaluated for structural integrity, microbial contamination, cellular viability, von Willebrand factor (VWF) production, cell proliferation and morphology under a range of subatmospheric pressures (75-200mmHg).
  
  
  RESULTS
  The bioreactor produced sustained subatmospheric pressures, which exerted a mechanical strain on the vascular scaffold. No microbial contamination was found during the study. The structural integrity of the vascular construct was maintained. There was no difference in cellular viability between control or subatmospheric pressure groups (p = 0.817). Cells continued to produce VWF under a range of subatmospheric pressures. Cells subjected to subatmospheric pressures of 125mmHg and 200mmHg exhibited higher levels of growth than cells in atmospheric pressure at 24 (p≤0.016) and 48 hour (p≤0.001). Negative pressure affected cellular morphology, which were more organised, elongated and expanded when exposed to subatmospheric pressure.
  
  
  CONCLUSIONS
  We have constructed and validated a novel subatmospheric bioreactor. The bioreactor maintained a continuous subatmospheric pressure to the vascular scaffolds in a stable, sterile and constant environment. The bioreactor exerted a strain on the vascular sheets, which was shown to alter cellular morphology and enhance cellular proliferation.
authors.affiliation: Department of Vascular Surgery, University Hospital Limerick, Limerick - Ireland.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Coakley
authors.affiliation: Department of Vascular Surgery, University Hospital Limerick, Limerick - Ireland.
authors.forename: Faisal M
authors.initials: FM
authors.lastname: Shaikh
authors.affiliation: The Statistical Consultancy Unit, School of Mathematical Sciences, University College Cork, Cork - Ireland.
authors.forename: Kathleen
authors.initials: K
authors.lastname: O'Sullivan
authors.affiliation: Department of Vascular Surgery, University Hospital Limerick, Limerick - Ireland.
authors.forename: Eamon G
authors.initials: EG
authors.lastname: Kavanagh
authors.affiliation: Department of Vascular Surgery, University Hospital Limerick, Limerick - Ireland.
authors.forename: Pierce A
authors.initials: PA
authors.lastname: Grace
authors.affiliation: Department of Biomedical Engineering, Khalifa University of Science, Technology & Research (KUSTAR), Abu Dhabi - United Arab Emirates.
authors.forename: Tim M
authors.initials: TM
authors.lastname: McGloughlin
mesh_terms: D058045:Artificial Cells; D019149:Bioreactors; D001808:Blood Vessels / Q000166:cytology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D011312:Pressure; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds