Combined effects of PLGA and vascular endothelial growth factor promote the healing of non-diabetic and diabetic wounds.

Published on Nov 1, 2015in Nanomedicine: Nanotechnology, Biology and Medicine5.182
· DOI :10.1016/J.NANO.2015.07.006
Kiran Kumar Chereddy7
Estimated H-index: 7
(UCL: Université catholique de Louvain),
Alessandra Lopes8
Estimated H-index: 8
(UCL: Université catholique de Louvain)
+ 8 AuthorsVéronique Préat79
Estimated H-index: 79
(UCL: Université catholique de Louvain)
Sources
Abstract
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. From the Clinical Editor 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.
Figures & Tables
Download
📖 Papers frequently viewed together
1,869 Citations
133 Citations
164 Citations
References33
Newest
#1Kiran Kumar Chereddy (UCL: Université catholique de Louvain)H-Index: 7
#2Charles-henry Her (UCL: Université catholique de Louvain)H-Index: 1
Last. Véronique Préat (UCL: Université catholique de Louvain)H-Index: 79
view all 14 authors...
Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained relea...
102 CitationsSource
#1Kelly E. Johnson (OSU: Ohio State University)H-Index: 3
#2Traci A. Wilgus (OSU: Ohio State University)H-Index: 25
Significance: Angiogenesis, the growth of new blood vessels from existing vessels, is an important aspect of the repair process. Restoration of blood flow to damaged tissues provides oxygen and nutrients required to support the growth and function of reparative cells. Vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic growth factors in the skin, and the amount of VEGF present in a wound can significantly impact healing. Recent Advances: The activity of VEGF was onc...
311 CitationsSource
#1Lars SteinstraesserH-Index: 45
#2Martin C. Lam (UCL: Université catholique de Louvain)H-Index: 4
Last. Gaëlle Vandermeulen (UCL: Université catholique de Louvain)H-Index: 20
view all 12 authors...
Host defense peptides, in particular LL-37, are emerging as potential therapeutics for promoting wound healing and inhibiting bacterial growth. However, effective delivery of the LL-37 peptide remains limiting. We hypothesized that skin-targeted electroporation of a plasmid encoding hCAP-18/LL-37 would promote the healing of wounds. The plasmid was efficiently delivered to full-thickness skin wounds by electroporation and it induced expression of LL-37 in the epithelium. It significantly acceler...
45 CitationsSource
#1Kiran Kumar Chereddy (UCL: Université catholique de Louvain)H-Index: 7
#2Régis Coco (UCL: Université catholique de Louvain)H-Index: 8
Last. Véronique Préat (UCL: Université catholique de Louvain)H-Index: 79
view all 7 authors...
Wound healing is a complex process involving many interdependent and overlapping sequences of physiological actions. The application of exogenous lactate released from poly (lactic-co-glycolic acid) (PLGA) polymer accelerated angiogenesis and wound healing processes. Curcumin is a well-known topical wound healing agent for both normal and diabetic-impaired wounds. Hence, we hypothesized that the PLGA nanoparticles encapsulating curcumin could much potentially accelerate the wound healing. In a f...
133 CitationsSource
#1Andrea Hasmann (Graz University of Technology)H-Index: 7
Last. Georg M. Guebitz (Graz University of Technology)H-Index: 59
view all 12 authors...
BackgroundNeutrophilic polymorphonuclear leukocytes play a crucial role in the host defence against bacterial and fungal infections. They participate in the inflammatory response through the liberation of peptides and enzymes like myeloperoxidase (MPO). Therefore, MPO has a potential as a marker enzyme for the diagnosis of wound infection.MethodsSubstrate specificities and reaction pathways of MPO were investigated for new MPO substrates: crystal violet, leuco crystal violet, fast blue RR (4-ben...
35 CitationsSource
#1Noah R Johnson (University of Pittsburgh)H-Index: 18
#2Yadong Wang (University of Pittsburgh)H-Index: 49
Wound healing is a dynamic process that relies on coordinated signaling molecules to succeed. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is proven to accelerate healing, however precise control over its application is necessary to reduce side effects and achieve desired therapeutic benefit. To achieve effective growth factor delivery we designed a bioactive heparin-based coacervate. In vitro, HB-EGF released from the coacervate delivery system displayed enhanced bi...
100 CitationsSource
#1Régis Coco (UCL: Université catholique de Louvain)H-Index: 8
#2Laurence Plapied (UCL: Université catholique de Louvain)H-Index: 7
Last. Véronique Préat (UCL: Université catholique de Louvain)H-Index: 79
view all 7 authors...
For inflammatory bowel disease (IBD) treatment, local delivery of molecules loaded in nanoparticles to the inflamed colon could be a promising strategy. The aim of this study was to investigate how drug-loaded polymeric nanoparticles target the site of inflammation and to analyse the influence of different colon-specific delivery strategies. Three different polymeric nanoparticles were formulated using ovalbumin (OVA) as a model drug. pH-sensitive nanoparticles were made with Eudragit(®) S100. M...
106 CitationsSource
Vascular endothelial growth factors (VEGFs) belong to the platelet-derived growth factor supergene family, and they play central roles in the regulation of angiogenesis and lymphangiogenesis. VEGF-A, the major factor for angiogenesis, binds to two tyrosine kinase (TK) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and regulates endothelial cell proliferation, migration, vascular permeability, secretion and other endothelial functions. VEGFR-2 exhibits a strong TK activity towards pro-angiog...
419 CitationsSource
#1Elaine Emmerson (University of Manchester)H-Index: 16
#2Laura Campbell (University of Manchester)H-Index: 17
Last. Matthew J. Hardman (University of Manchester)H-Index: 34
view all 8 authors...
Although it is understood that endogenous IGF-1 is involved in the wound repair process, the effects of exogenous IGF-1 administration on wound repair remain largely unclear. In addition, the signaling links between IGF-1 receptor (IGF-1R) and estrogen receptors (ERs), which have been elucidated in other systems, have yet to be explored in the context of skin repair. In this study, we show that locally administered IGF-1 promotes wound repair in an estrogen-deprived animal model, the ovariectomi...
49 CitationsSource
#1Julie Vanacker (UCL: Université catholique de Louvain)H-Index: 18
#2Valérie Luyckx (UCL: Université catholique de Louvain)H-Index: 12
Last. Christiani Andrade Amorim (UCL: Université catholique de Louvain)H-Index: 34
view all 8 authors...
For women diagnosed with leukemia, transplantation of cryopreserved ovarian tissue after disease remission is not advisable. Therefore, to restore fertility in these patients, we aim to develop a biodegradable artificial ovary that offers an environment where isolated follicles and ovarian cells (OCs) can survive and grow. Four NMRI mice were ovariectomized and their ovaries used to isolate OCs. Groups of 50,000 OCs were embedded in an alginate-matrigel matrix for further fixation (fresh control...
92 CitationsSource
Cited By47
Newest
#1Vyshnavi Tallapaneni (Jagadguru Sri Shivarathreeswara University)H-Index: 1
#2C. Kalaivani (Jagadguru Sri Shivarathreeswara University)
Last. Veera Venkata Satyanarayana Reddy Karri (Jagadguru Sri Shivarathreeswara University)H-Index: 12
view all 6 authors...
Diabetic wound (DW) is one of the leading complications of patients having a long history of uncontrolled diabetes. Moreover, it also imposes an economic burden on people suffering from wounds to manage the treatment. The major impending factors in the treatment of DW are infection, prolonged inflammation and decreased oxygen levels. Since these non-healing wounds are associated with an extended recovery period, the existing therapies provide treatment for a limited period only. The areas covere...
Source
#1Ruan Na (HUST: Huazhong University of Science and Technology)
OBJECTIVE The burden of the management of problematic skin wounds characterised by a compromised skin barrier is growing rapidly. Almost six million patients are affected in the US alone, with an estimated market of $25 billion annually. There is an urgent requirement for efficient mechanism-based treatments and more efficacious drug delivery systems. Novel strategies are needed for faster healing by reducing infection, moisturising the wound, stimulating the healing mechanisms, speeding up woun...
Source
Last. Soledad Pérez-Amodio (UPC: Polytechnic University of Catalonia)H-Index: 6
view all 5 authors...
Significance The incidence of chronic wound is increasing due to our aging population and the augment of people afflicting with diabetes. With the extended knowledge on the biological mechanisms underlying these diseases, there is a novel influx of medical technologies into the conventional wound care market. Recent Advances Several nanotechnologies have been developed demonstrating unique characteristics that address specific problems related to wound repair mechanisms. In this review, we focus...
3 CitationsSource
#1Que BaiH-Index: 1
#2Kai HanH-Index: 2
Last. Tingli LuH-Index: 16
view all 7 authors...
Diabetic wound shows delayed and incomplete healing processes, which in turn exposes patients to an environment with a high risk of infection. This article has summarized current developments of nanoparticles/hydrogels and nanotechnology used for promoting the wound healing process in either diabetic animal models or patients with diabetes mellitus. These nanoparticles/hydrogels promote diabetic wound healing by loading bioactive molecules (such as growth factors, genes, proteins/peptides, stem ...
1 CitationsSource
Source
#1Hosna Zare (MUMS: Mashhad University of Medical Sciences)H-Index: 6
#2Majid Rezayi (MUMS: Mashhad University of Medical Sciences)H-Index: 25
Last. Mojtaba Sankian (MUMS: Mashhad University of Medical Sciences)H-Index: 22
view all 9 authors...
Diabetic foot ulcers (DFUs) are chronic severe complications of diabetes disease and remain a worldwide clinical challenge with social and economic consequences. Diabetic wounds can cause infection, amputation of lower extremities, and even death. Several factors including impaired angiogenesis, vascular insufficiency, and bacterial infections result in a delayed process of wound healing in diabetic patients. Treatment of wound infections using traditional antibiotics has become a critical statu...
1 CitationsSource
#1Corinne N. Riggin (UPenn: University of Pennsylvania)H-Index: 10
#2Ashley B. Rodriguez (UPenn: University of Pennsylvania)H-Index: 5
Last. Louis J. Soslowsky (UPenn: University of Pennsylvania)H-Index: 78
view all 8 authors...
Tendons are relatively hypovascular but become hypervascular during both injury and degeneration. This is due to the angiogenic response, or the formation of new blood vessels, to tissue injury. The objective of this study was to evaluate the effect of vascular modulation in the rat Achilles tendons during healing. Fischer rats received a bilateral Achilles incisional injury followed by local injections of vascular endothelial growth factor (VEGF), anti-VEGF antibody (B20.4-1-1), or saline (SAL)...
1 CitationsSource
#2Kuldeep K. Bansal (Åbo Akademi University)H-Index: 9
Last. Neelesh Kumar MehraH-Index: 1
view all 7 authors...
The topical route is the most preferred one for administering drugs to eyes, skin and wounds for reaching enhanced efficacy and to improve patient compliance. Topical administration of drugs via conventional dosage forms such as solutions, creams and so forth to the eyes is associated with very low bioavailability (less than 5%) and hence, we cannot rely on these for delivering drugs to eyes more efficiently. An intravitreal injection is another popular drug delivery regime but is associated wit...
3 CitationsSource
#1Ayan Nurkesh (NU: Nazarbayev University)H-Index: 4
#2Alexandr Jaguparov (NU: Nazarbayev University)H-Index: 2
Last. Arman Saparov (NU: Nazarbayev University)H-Index: 13
view all 4 authors...
Bioengineered materials are widely utilized due to their biocompatibility and degradability, as well as their moisturizing and antibacterial properties. One field of their application in medicine is to treat wounds by promoting tissue regeneration and improving wound healing. In addition to creating a physical and chemical barrier against primary infection, the mechanical stability of the porous structure of biomaterials provides an extracellular matrix-like niche for cells. Growth factors and c...
3 CitationsSource
#1Maryam Salmani Jajaei (IAU: Islamic Azad University)
#2Sonia Rafiei (IAU: Islamic Azad University)
Abstract In this present work, synthesized of poly (lactide-glycolide) was carried out via two separate solvent evaporation methods for evaluating the effect of particle size in cancer treatment. By changing the percentage of polymer in dispersed phase solution and percentage of poly (vinyl alcohol) in continuous phase, particles with different morphology and dimensions were prepared. The particles with a low percentage of stabilizer had rough surfaces and larger sizes. By increasing the percent...
Source