Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions

Table 2

Controlled release VEGF and BMPs.

Authors	BMPs	Carrier	Models	Combination delivery	Ratio; (VEGF/BMP)	Bone formation in combined delivery group
Kakudo et al. 2006 [41]	BMP2	Collagen	Rat; Intramuscular (3 weeks)	Simultaneous	1 : 2	Enhanced (compared to BMP2 alone); [41]
Patel et al. 2008 [42]	BMP2	Gelatin	Rat; Calvarial defect (4/12 weeks)	Simultaneous	6 : 1	Enhanced at 4 weeks (compared to BMP2 alone); No significant difference at 12 weeks (compared to BMP2 alone); [42]
Kempen et al. 2009 [43]	BMP2	PLGA-BMP2 (sustained release); Gelatin-VEGF (fast release)	Rat; Subcutaneous (8 weeks); Segmental femoral defect (8 weeks)	Sequential	1 : 3.3	Ectopic: enhanced (compared to BMP2 alone); Orthotopic: no significant difference (compared to BMP2 alone); [43]
Young et al. 2009 [44]	BMP2	Gelatin	Rat; Calvarial defect (12 weeks)	Simultaneous	6/12/24 : 1	No significant difference (compared to BMP2 alone); [44]
Roldán et al. 2010 [45]	BMP7	BCP scaffold (growth factors injected in the scaffolds)	Mice; Subcutaneous (12 weeks)	Simultaneous	2 : 5	No significant difference (compared to BMP7 alone); [45]
Zhang et al. 2011 [7]	BMP2	Silk hydrogels	Rabbits; Sinus floor elevation model (4/12 weeks)	Simultaneous	2 : 3	Enhanced (compared to BMP2 alone); [7]
Geuze et al. 2012 [13]	BMP2	PLGA-VEGF/BMP2 (fast release); Gelatin-VEGF/BMP2 (sustained release)	Dog; Ectopic: intramuscular (9 weeks); Orthotopic site: ulnar defect (9 weeks)	Sequential or simultaneous	1 : 30	No significant enhancement effect (compared to BMP2 alone); [13]
Hernández et al. 2012 [46]	BMP2	PLGA	Rabbit; Intramedullary femur defect (4/12 weeks)	Simultaneous	1 : 10/50	Enhanced at 4 weeks (compared to BMP2 alone); No significant difference at 12 weeks (compared to BMP2 alone); [46]
Das et al. 2015 [47]	BMP6	PLGA	Rat; Mandibular defect (2/8/12 weeks)	Simultaneous	1 : 1	Enhanced (compared to BMP6 alone); [47]
Lv et al. 2015 [48]	BMP2	Fibrin glue (fast release)	Rabbit; Femoral condyle defect (4 weeks)	Simultaneous	1 : 100	No synergistic effect; (compared to BMP2 alone); [48]