Table 2.

Summary of VEGF delivery and cardiac repair in the last 2 years.

DDS		COMPOSITION	ANGIOGENIC FACTOR/S	PREPARATION METHOD	ANGIOGNENIC EFFICACY ASSAY	AUTHOR'S CONCLUSION	REF.
SCAFFOLD	surface crosslinked Heparin	polycaprolactone	VEGF	Solvent casting and particulate leaching method	Subcutaneous implant model in mice	Modification of the scaffold with heparin improves VEGF efficacy	37
	hollow-fiber membrane	cellulose acetate	VEGF & S1P	Double injection extrusion/ precipitation method	Subcutaneous implant model in mice	System capable of exploring sequential delivery of angiogenic factors. Sequential delivery of VEGF followed by S1P resulted in recruitment of more ECs and higher maturation index	43
	biomimetic hydrogel (adhesion peptide sequence RGDS)	PEG diacrylate	VEGF	Photopolymerization	In vitro (HUVECs and hMECs)	The system promotes EC proliferation, migration and viability maintenance	44
	patch with covalently immobilized VEGF	collagen	VEGF	Commercial scaffold	Right ventricular free wall resection and replacement with the scaffold	Collagen scaffold with covalently immobilized VEGF improved tissue formation	32
	hydrogel with surface crosslinked Heparin	star-PEG	VEGF & FGF-2	Cross linking	In vitro (HUVECs) and Chicken chorioallantoin membrane angiogénesis assay	Angiogenic activity superior to the administration of single factors	45, 46
	hydrogel	alginate	VEGF	Cross linking	Hindlimb ischemia in mice		47
	covalently immobilized factors	collagen	VEGF & Ang-1	Commercial scaffold	Chicken chorioallantoin membrane angiogenesis assay	Scaffolds with co-immobilized VEGF and Ang-1 further improved angiogenesis as compared to independently immobilized VEGF or Ang-1	31
	composite scaffold	Poly(ether)urethane-polydimethylsiloxane -fibrin	VEGF & bFGF	Spray-phase inversion method	Subcutaneous implant and unilateral hind limb ischemia model in rat	Incorporation of VEGF, bFGF and heparin in the composite scaffold enhances angiogenesis	38
	temperature sensitive injectable hydrogel	PVL-b-PEG-b-PVL	VEGF	Metal-free cationic method	Myocardial infarction rat model (coronary artery ligation)	The system preserved ventricular function by stabilizing the infarct and reducing angiogenesis	41
	fibrous membranes	Dextran/PLGA	VEGF	Coaxial electrospinning	In vitro	The system positively promotes cell proliferation	48
	dual layered scaffold combined with an osmotic release mechanism	Poly(trimethylene carbonate)	VEGF & HGF	Cross linking	In vitro (HAECs)	System able to release combined GFs at similar rates, and at controllable sequences	49
PARTICLES	NPs	Hyaluronic acid/chitosan	VEGF & PDGF-BB	Ionic gelification technique	-	NPs entrap efficiently both factors. PDGF-BB is released in a sustained manner over 1 week and VEGF within the first 24 hours.	50
		PLGA/heparin/fibrin	VEGF	Spontaneous emulsion solvent diffusion method	Rabbit ischemic hind limb	The system strongly increases the in vivo therapeutic angiogenic effects of VEGF	51
		PLGA	VEGF	Modification of the double emulsion method	Hindlimb ischemia in mice	Feasibility of the system to produce a more viogorous revascularization when compared with free VEGF administration	52
	MPs	PLGA	VEGF	Double emulsion/solvent evaporation method	In vitro (HUVECs)	The system allows VEGF encapsulation and bioactive protein release up to 21 days	53
		PLGA	VEGF	Double emulsion/solvent evaporation method	Myocardial infarction rat model (coronary artery ligation)		54
		Collagen	VEGF	Cross linking	In vitro (HUVECs)	The system allows VEGF encapsulation and bioactive protein release up to 4 weeks	55
PARTICLES- SCAFFOLD	MPs MPs-Scaffold	PLGA (MPs) PLGA-N-methyl pyrrolidone (scaffold)	VEGF	MPs: spray dry Scaffold: gelification	Murine model of peripheral angiogenesis	Both formulations provide a method to incite neovascularization from a single injection	56
	NPs Scaffolds (hydrogel or polymeric) NPs-Scaffold (hydrogel or polymeric)	NPs: Dextran-sulfate/chitosan Scaffold: Matrigel® or PLGA	VEGF	NPs: complex formation and coacervation Scaffold: gas foaming/particulate leaching method (Matrigel®: commercially obtained)	Subcutaneous injection (NPs-Matrigel®) NPs-PLGA scaffolds implanted into the intraperioneal fat pad of mice	Angiogenesis was clearly improved by VEGF encapsulation and further incorporation into implants, compared to direct VEGF incorporation into implants	57
	MPs-Scaffold co-administered with ECs	Alginate MPs collagen/fibronectin gel	VEGF & MCP-1	Cross linking	Subcutaneous implant model in mice	Delivery of multiple therapeutic proteins to enhance the efficacy of cell-based vascularization	58
OTHER	Polymeric injectable carrier	Poly(trimethylene carbonate)	VEGF	-	Subcutaneous injection in rat	The approach has potential for providing effective, local, bioactive growth factor delivery.	59
	Collagen patches	Collagen	VEGF	Collagen binding domain is fused to VEGF	Myocardial implantation	Patches improve left ventricular cardiac function and increase the vascular density	60