title: Combined effects of PLGA and vascular endothelial growth factor promote the healing of non-diabetic and diabetic wounds.
abstract: Growth factor therapies to induce angiogenesis and thereby enhance the blood perfusion, hold tremendous potential to address the shortcomings of current impaired wound care modalities. Vascular endothelial growth factor stimulates (VEGF) wound healing via multiple mechanisms. Poly(lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. Hence, we hypothesized that the administration of VEGF encapsulated in PLGA nanoparticles (PLGA-VEGF NP) would promote fast healing due to the sustained and combined effects of VEGF and lactate. In a splinted mouse full thickness excision model, compared with untreated, VEGF and PLGA NP, PLGA-VEGF NP treated wounds showed significant granulation tissue formation with higher collagen content, re-epithelialization and angiogenesis. The cellular and molecular studies revealed that PLGA-VEGF NP enhanced the proliferation and migration of keratinocytes and upregulated the expression of VEGFR2 at mRNA level. We demonstrated the combined effects of lactate and VEGF for active healing of non-diabetic and diabetic wounds.
  
  
  BACKGROUND
  The study of wound healing has been under a tremendous amount of research over recent years. In diabetic wounds, vasculopathy leading to localized ischemia would often result in delayed  wound healing. In this article, the authors encapsulated vascular endothelial growth factor stimulates (VEGF) in PLGA nanoparticles and studies the potential pro-healing effects. It was found that the combination of these two components provided synergistic actions for healing. The encouraging results should provide a basis for combination therapy in the future.
authors.affiliation: Louvain Drug Research Institute (LDRI) Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Chereddy
authors.affiliation: Louvain Drug Research Institute (LDRI) Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lopes
authors.affiliation: Louvain Drug Research Institute (LDRI) Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Salome
authors.initials: S
authors.lastname: Koussoroplis
authors.affiliation: Institut de Recherche Expérimentale et Clinique (IREC) Pole of Pharmacology, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Valéry
authors.initials: V
authors.lastname: Payen
authors.affiliation: Environmental Technology Department, School of Energy, Environment and Agrifood, Cranfield University, Bedford, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Moia
authors.affiliation: Environmental Technology Department, School of Energy, Environment and Agrifood, Cranfield University, Bedford, UK.
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institut de Recherche Expérimentale et Clinique (IREC) Pole of Pharmacology, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.affiliation: VIB Vesalius Research Center, KU Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.affiliation: Louvain Drug Research Institute (LDRI) Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: des Rieux
authors.affiliation: Louvain Drug Research Institute (LDRI) Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vandermeulen
authors.affiliation: Louvain Drug Research Institute (LDRI) Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019344:Lactic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen; D009195:Peroxidase
keywords: Diabetic wound healing; Lactate; Nanoparticles; Poly(lactic-co-glycolic acid) (PLGA); VEGF