“…Alternatively, combinations with VEGF or TGF-β3 (Ripamonti et al, 2010) constitute mutualistic approaches where the angiogenic factor induces vessel ingrowth into the defect (2 fold (Zhang et al, 2010a)), the chondrogenic factor induces cartilaginous matrix production to fill the defect void, and the osteogenic factor induces resultant callus mineralisation and eventual bone formation (three lineages important for recapitulation of the in vivo bone healing cascade). Other factors and compounds used in combination with BMP-7 include BBP , FGF-2 , insulin-like growth factor 1 (IGF-1) , pamidronate (Yu et al, 2010a), PDGF (Zhang et al, 2012a), PTH (1-34) (Morgan et al, 2008), TGF-β1 (Ripamonti et al, 2001b) and thrombospondin 1 (TSP-1) (Gelse et al, 2011). Taken together these combinations have demonstrated increased defect regeneration from 1.4 to 5.3 fold in large animals (Ripamonti et al, 2010;Zhang et al, 2009b), and 1.2 to 15 fold in small animals Zhang et al, 2012a).…”