Therapeutic role of growth factors in treating diabetic wound

Table 2 Biomaterial systems applied for the delivery of growth factors in diabetic wounds

Therapeutic agents	Delivery system and route	Animal type	Wound size	Response on wound closure	Ref.
PDGF/TGF-α	Gel/topical spraying to wound bed	C57BL/KsJ-db/db mouse	Full-thickness wound measuring 1.5 cm × 1.5 cm	Accelerated wound closure at 15-21 d	[262]
bFGF	Chitosan film/topical using	C57BL/KsJ-db/db mice	Full-thickness wound (1.6 cm diameter)	Reduced wound area and increased ECM formation	[318]
bFGF	Chitosan/hydrogels implant	C57BL/KsJ-db/db mice	Full-thickness wounds (about 100 mm2)	80% wound closure by 12 d	[319]
pDNA TGF-β1	PEG-PLGA-PEG/hydrogels implant	C57BKS.Cg-m +/+ Leprdb female mice	Full-thickness wounds (7 mm × 7 mm)	Accelerated wound closure at 5 d	[280]
bFGF	Chitosan, hydrogel/topical using	C57BL/KsJ-db/db mice	Full-thickness circular wounds (about 100 mm2)	Accelerated tissue filling rate of wounds and increased number of CD-34-positive vessels	[320]
PDGF-BB	Carboxymethyl cellulose hydrogel/topical using	C57/Bl6 wild-type mice and lep/r db/db homozygous diabetic mice	Either a 0.6 cm2, 1.0 cm2, or 1.5 cm2 full-thickness area of skin	Accelerated healing by enhanced granulation tissue formationand angiogenesis	[321]
bFGF	Collagen, PGA/porous scaffolds implant	C57BLKS/J Iar- + Leprdb/ + Leprdb	Full-thickness wounds (6 mm diameter	NA	[322]
rhPDGF	Gel/topical spraying to wound bed	Wistar diabetic rats	Full-thickness dermal wounds of 2.54 cm2 (1.8 cm diameter)	Outstanding re-epithelialization within the first 7 d	[323]
bFGF	Chondroitin-6-sulfate, heparin/hydrogels implant	C57BLKs/J-m1/db, db/db mice, heterozygous (m1/db)	Full-thickness wounds (1.6 cm diameter)	89% wound closure by 2 wk	[324]
rhEGF	PCL, PCL-PEG/non-woven mesh (electrospun) implant		Ful-thickness wounds (0.8 cm diameter)	Accelerated wound closure at 7 d	[325]
PDGF	5% polyethylene glycol gel/intradermal injection	Wistar rats	Full-thickness wounds (1.8 cm diameter)	Significant wound improvement within 14 d	[237]
aFGF	Collagen, chitosan/porous scaffolds implant	SD rats	Whole skin layer round wounds (1.8 cm diameter)	Complete healing at 14 d	[326]
rhEGF	PLGA microspheres	SD rats	Full-thickness dermal wounds (2.54 cm2, 1.9 cm diameter)	90% healing rate on the 14th day	[327]
Collagen-binding domain (CBD)-VEGF	Collagen domain/praye onto the traumatic surface	SD rats	Full-thickness wounds (2 cm × 2.5 cm)	95% healing rate basically reached after 21 d	[328]
rhEGF	PLGA nanoparticles/topical spraying to wound bed	SD rats	Full-thickness dermal wounds (1.8 cm in diameter)	Complete wound closure by 21 d	[329]
bFGF	PELA/non-woven mesh (electrospun) implant	SD rats	Full-thickness circular wounds (about 250 mm2 each)	Complete wound closure by 3 wk	[330]
rhEGF	Dextrin conjugated/topical using	BKS.Cg-m a/a +/+ Leprdb/J db/db mice	Full-thickness wounds (10 mm × 10 mm)	Accelerated wound closure, neo-dermal tissue formation, increased granulation tissue deposition and angiogenesis	[331]
EGF	Collagen, hyaluronic acid/porous scaffolds implant	BKS.Cg-+Leprdb/+Leprdb (db/db) mice	Full-thickness wounds (15 mm × 20 mm)	N/A	[332]
pDNA bFGF	PELA/electrospun mesh implant	Male SD rats	Full-thickness wounds (about 250 mm2)	Complete wound closure by 3 wk	[333]
bFGF	Collagen, gelatine/porous scaffolds implant	BKS.Cg- + Leprdb/+ Leprdb/Jcl	8 mm diameter and 3 mm thickness	NA	[334]
VEGF/bFGF	PLGA nps, fibrin/porous scaffolds implant	BKS.Cg-m+/+ Lepr, db/db	Full-thickness dermal wound (0.8 cm in diameter)	85% wound closure at 15 d	[335]
rhEGF	PLGA-alginate microspheres/intralesional injection	Wistar rats	Full-thickness dermal wound (1 cm in diameter)	90% wound closure at 11 d	[336]
rhEGF	Lipid nanocarriers/topical application to wound bed	BKS.Cg-m+/+Lepr 286 db/J	Full-thickness wounds 0.8 cm in diameter	95% wound closure at 15 d	[337]
VEGF, bFGF, EGF, PDGF	Collagen, hyaluronic acid, gelatine nps/non-woven mesh (electrospun) implant	SD rats	Full thickness wound (diameter of 15 mm)	Complete wound closure by 4 wk	[338]
pDNA VEGF	Hyaluronic acid/hydrogels implant	db/db mice	Full-thickness wounds were then generated using a 6 mm biopsy punch (4 mm for wounds on smaller balb/c mice)	Induction of wound closure by day 8-10	[339]
VEGF	PLGA nanoparticles/intradermal injection	db/db mice	Full thickness excisional wounds, two (8 mm diameter) and four (6 mm diameter)	Complete wound closure by 19 d	[340]
VEGF, PDGF	Poly (β-amino esters), poly (acrylic acid), heparan sulfate/woven nylon mesh implant	db/db mice	Full-thickness skin wound	Accelerated wound closure at 14 d	[341]
rhEGF	NaCMCh-rhEGF/hydrogels implant	SD rats	Full-thickness wounds (2 cm diameter, 3.14 cm2 circular area)	Wound healed in day 15	[342]
rhEGF	PU/porous scaffolds implant	SD rats	Full-thickness wounds (dimensions of 2 cm × 2 cm)	97% wound closure at 21 d	[343]
VEGF	PEG, heparin/hydrogels implant	Cg-m +/+ Leprdb/J (db/db) mice	Full-thickness punch biopsy wound	-	[344]
rhPDGF	PLGA/Non-woven mesh (electrospun) implant	SD rats	Full-thickness excision (8.0 mm in diameter)	Complete wound closure by 14 d	[345]
bFGF	Chitosan, hydrogel + heparin/topical using	C57BL/KsJ-db/db mice	-	Significant angiogenesis and collateral circulation construction	[346]
bFGF	Gelatin hydrogel microspheres/topical injection	C57BL/KsJ-db/db mice	Full-thickness wounds (10 mm in diameter)	Accelerated diabetic skin wound healing and reduced scarring	[347]
bFGF	Acidic gelatin sheet/topical coverage	C57BL/KsJ-db/db mice	Full-thickness wound (1.5 cm × 1.5 cm)	Promoted neoepithelialization, granulation, neovascularization, and wound healing	[348]

VEGF: Vascular endothelial growth factor; PDGF: Platelet-derived growth factor; EGF: Epidermal growth factor; FGF: Fibroblast growth factor; rhEGF: Recombinant human epidermal growth factor.