Thorac Cardiovasc Surg 2013; 61 - SC83
DOI: 10.1055/s-0032-1332581

The dosage dependence of VEGF stimulation on scaffold neovascularisation

S Dobner 1, 2, NH Davies 1, D Bezuidenhout 1, C Schmidt 1, M Beck 3, H Reichenspurner 2, AH Zisch 4, 5, 6, P Zilla 1
  • 1Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Cape Town, South Africa
  • 2Universitäres Herzzentrum Hamburg, Klinik und Poliklinik für Herz- und Gefäßchirurgie, Hamburg, Germany
  • 3Materials and Bioscience Center, Medtronic Inc., Minneapolis, United States
  • 4University Hospital Zurich, Department of Obstetrics, Zurich, Switzerland
  • 5Zurich Center for Integrative Human Physiology, Zurich, Switzerland
  • 6Department of Materials, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland

Aims: Growth factors are often used in tissue regeneration to stimulate vascularisation of polymeric scaffolds, with vascular endothelial growth factor (VEGF) having been extensively studied for short-term vessel ingrowth.

Methods and results: We have evaluated the effect of different concentrations of VEGF on the vascularisation of a porous scaffold in the short-, intermediate- and long-term, by delivering 15, 150 and 1500 ng VEGF/day to polyurethane scaffolds by osmotic pumps for up to 6 weeks. An increased vascularisation months after termination of VEGF delivery was only achieved with 150 ng/day (46%, p < 0.05). This dosage consistently showed elevated levels of vascularisation (144, 125, 160 and 60% above PBS controls at 10, 20, 30 and 42 days, respectively, p < 0.05), whilst the vessels induced by the highest dosage, though initially maximally elevated (265 and 270% at 10 and 20 days, p < 0.05) tended to regress after 20 days of VEGF delivery. Pericyte coverage was decreased at 20 days for the highest dosage (30%, p < 0.05). Lectin perfusion demonstrated that vessels within the scaffold were connected to the host vasculature at all time points and perfusion was substantially raised by VEGF delivery at day 20.

Conclusion: These results suggest concentration of VEGF plays a critical role in the nature and persistence of vasculature formed in a tissue regenerative scaffold.