The stimulation of angiogenesis and collagen deposition by copper

Copper is known to trigger endothelial cells towards angiogenesis. Different approaches have been investigated to develop vascularisation in biomaterials. The angiogenic and healing potential of copper ions in combination with two major angiogenic factors was examined. A 3D culture system in which, under stimulation by FGF-2 and to a lesser degree with VEGF, endothelial cells assembled into structures resembling to an angiogenic process was used. The combination of CuSO4 with increasing doses of VEGF or FGF-2 enhanced the complexity of angiogenic networks in a significant manner. In vivo studies were also conducted by incorporating FGF-2 with CuSO4 in a cylindrical collagen-based scaffold. CuSO4 enhanced significantly the invasion of microvessel compared to control implants and to 20 ng FGF-2 ± CuSO4. Vascular infiltration was also significantly improved by combination of CuSO4 with FGF-2, compared to FGF-2 alone (0.2 and 1 μg). Nevertheless, in comparison with CuSO4 alone, there was a significant increase only with 1 μg of FGF-2 combined with CuSO4. Significantly, collagen fiber deposition was enhanced following the combinatory loading in comparison to that with FGF-2 alone but not with CuSO4 only. Thus, copper associated with growth factors may have synergistic effects which are highly attractive in the fields of tissue engineering (e.g., bone) and biomaterials.