title: Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice.
abstract: Diabetic skin ulcers are difficult to heal spontaneously due to the reduced levels and activity of endogenous growth factors. Recombinant human vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are known to stimulate cell proliferation and accelerate wound healing. Direct delivery of VEGF and bFGF at the wound site in a sustained and controllable way without loss of bioactivity would enhance their biological effects. The aim of this study was to develop a poly(ether)urethane-polydimethylsiloxane/fibrin-based scaffold containing poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with VEGF and bFGF (scaffold/GF-loaded NPs) and to evaluate its wound healing properties in genetically diabetic mice (db/db). The scaffold application on full-thickness dorsal skin wounds significantly accelerated wound closure at day 15 compared to scaffolds without growth factors (control scaffold) or containing unloaded PLGA nanoparticles (scaffold/unloaded NPs). However, the closure rate was similar to that observed in mice treated with scaffolds containing free VEGF and bFGF (scaffold/GFs). Both scaffolds containing growth factors induced complete re-epithelialization, with enhanced granulation tissue formation/maturity and collagen deposition compared to the other groups, as revealed by histological analysis. The ability of the scaffold/GF-loaded NPs to promote wound healing in a diabetic mouse model suggests its potential use as a dressing in patients with diabetic foot ulcers.
authors.affiliation: Laboratory of Biomaterials & Graft Technology, Institute of Clinical Physiology, National Research Council, Via Aurelia Sud, 54100 Massa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Losi
authors.forename: Enrica
authors.initials: E
authors.lastname: Briganti
authors.forename: Cesare
authors.initials: C
authors.lastname: Errico
authors.forename: Antonella
authors.initials: A
authors.lastname: Lisella
authors.forename: Elena
authors.initials: E
authors.lastname: Sanguinetti
authors.forename: Federica
authors.initials: F
authors.lastname: Chiellini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Soldani
mesh_terms: D000818:Animals; D001458:Bandages; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D017719:Diabetic Foot / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005337:Fibrin / Q000737:chemistry*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D051379:Mice; D008822:Mice, Transgenic; D054457:Tissue Scaffolds; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D005337:Fibrin