Research Article

Cellular and Molecular Life Sciences

, Volume 65, Issue 1, pp 177-186

Spatially defined oxygen gradients and vascular endothelial growth factor expression in an engineered 3D cell model

  • U. CheemaAffiliated withTissue Repair and Engineering Centre, Institute of Orthopaedics and Musculoskeletal Sciences, University College London Email author 
  • , R. A. BrownAffiliated withTissue Repair and Engineering Centre, Institute of Orthopaedics and Musculoskeletal Sciences, University College London
  • , B. AlpAffiliated withTissue Repair and Engineering Centre, Institute of Orthopaedics and Musculoskeletal Sciences, University College London
  • , A. J. MacRobertAffiliated withNational Medical Laser Centre, Royal Free and University College Medical School

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract.

Tissue hypoxia results in rapid angiogenesis in vivo, triggered by angiogenic proteins, including vascular endothelial growth factor (VEGF). Current views of tissue viability are founded on whether ‘deeper-lying’ cells receive sufficient nutrients and oxygen for normal activity and ultimately survival. For intact tissues, levels of such essential nutrients are governed by micro-vascular perfusion. However, there have been few effective quantitatively defined 3D models, which enable testing of the interplay or interdependence of matrix and cell density, and path diffusion on oxygen consumption in vitro. As a result, concepts on cell vulnerability to low oxygen levels, together with the nature of cellular responses are ill defined. The present study has adapted a novel, optical fibre-based system for in situ, real-time oxygen monitoring within three-dimensionally-spiralled cellular collagen constructs, which were then unfurled to enable quantitative, spatial measurements of VEGF production in different parts of the same construct exposed to different oxygen levels. A VEGF response was elicited by cells exposed to low oxygen levels (20 mmHg), primarily within the construct core.

Keywords.

Oxygen monitoring cellular hypoxia 3D culture tissue construct VEGF plastic compression collagen cell death tissue engineering