scholarly journals Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration

2019 ◽  
Author(s):  
Martina Balli ◽  
Francesca Vitali ◽  
Adrian Janiszewski ◽  
Ellen Caluwé ◽  
Alvaro Cortés-Calabuig ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
Skin Lesions ◽  
Wound Healing Process ◽  
Primary Fibroblast ◽  
Fibroblast Migration ◽  
Healing Response ◽  
Wound Healing Response

AbstractDefective fibroblast migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective treatment able to improve wound healing capacity. However, the molecular mechanisms connecting their beneficial outcomes with the wound healing process are still unrevealed. Here, we show that AMG modulates primary fibroblast migration and accelerates skin re-epithelialization without affecting cell proliferation. We demonstrate that AMG is enriched in a pool of WH-associated growth factors that may provide the initiation signal for a faster endogenous wound healing response. This, in turn leads to increased cell migration rate by elevating activity of extracellular signal-regulated kinase (ERK) pathway and subsequent activation of matrix metalloproteinase expression and their extracellular enzymatic activity. Moreover, AMG-treated wounds showed increased granulation tissue formation and organized collagen content. Overall, we shed light on AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process.

scholarly journals Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration

2019 ◽  
Vol 27 (5) ◽  
pp. 1520-1538 ◽  
Author(s):  
Martina Balli ◽  
Francesca Vitali ◽  
Adrian Janiszewski ◽  
Ellen Caluwé ◽  
Alvaro Cortés-Calabuig ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Molecular Mechanism ◽  
Healing Process ◽  
Skin Lesions ◽  
Wound Healing Process ◽  
Transcriptional Signature ◽  
Beneficial Effects ◽  
Healing Response ◽  
Wound Healing Response

Abstract Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which AMG exhibits its beneficial effects remains unrevealed. Herein we show that AMG improves skin re-epithelialization by accelerating the migration of fibroblasts and keratinocytes. More specifically, AMG-treated wounds showed improvement of indispensable events associated with successful wound healing such as granulation tissue formation, organized collagen content, and newly formed blood vessels. We demonstrate that AMG is enriched with a pool of WH-associated growth factors that may provide the starting signal for a faster endogenous wound healing response. This work links the increased cell migration rate to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, which is followed by an increase in matrix metalloproteinase expression and their extracellular enzymatic activity. Overall we reveal the AMG-mediated wound healing transcriptional signature and shed light on the AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process. In this way, we present a framework for future improvements in AMG therapy for skin tissue regeneration applications.

Identifying New Pathways and Targets for Wound Healing and Therapeutics from Natural Sources

2021 ◽  
Vol 18 ◽  
Author(s):  
Xinchi Feng ◽  
Jinsong Hao
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Wound Care ◽  
Healing Process ◽  
Unmet Need ◽  
Wound Dressings ◽  
Wound Healing Process ◽  
Natural Sources ◽  
Viable Approach

: Chronic wounds remain a significant public problem and the development of wound treatments has been a research focus for the past few decades. Despite advances in the products derived from endogenous substances involved in a wound healing process (e.g. growth factors, stem cells, and extracellular matrix), effective and safe wound therapeutics are still limited. There is an unmet need to develop new therapeutics. Various new pathways and targets have been identified and could become a molecular target in designing novel wound agents. Importantly, many existing drugs that target these newly identified pathways could be repositioned for wound therapy, which will facilitate fast translation of research findings to clinical applications. This review discusses the newly identified pathways/targets and their potential uses in the development of wound therapeutics. Some herbs and amphibian skins have been traditionally used for wound repairs and their active ingredients have been found to act in these new pathways. Hence, screening these natural products for novel wound therapeutics remains a viable approach. The outcomes of wound care using natural wound therapeutics could be improved if we can better understand their cellular and molecular mechanisms and fabricate them in appropriate formulations, such as using novel wound dressings and nano-engineered materials. Therefore, we also provide an update on the advances in the wound therapeutics from natural sources. Overall, this review offers new insights into novel wound therapeutics.

scholarly journals Wound Healing Activity of the Essential Oil of Bursera morelensis, in Mice

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1795
Author(s):  
Judith Salas-Oropeza ◽  
Manuel Jimenez-Estrada ◽  
Armando Perez-Torres ◽  
Andres Eliu Castell-Rodriguez ◽  
Rodolfo Becerril-Millan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Essential Oil ◽  
Cell Viability ◽  
Murine Model ◽  
Biological Activities ◽  
Healing Process ◽  
In Vitro Tests ◽  
Wound Healing Process ◽  
Fibroblast Migration

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. It is an endemic tree known as “aceitillo”, and the antibacterial and antifungal activity of its essential oil has been verified; it also acts as an anti-inflammatory. All of these reported biological activities make the essential oil of B. morelensis a candidate to accelerate the wound-healing process. The objective was to determine the wound-healing properties of B. morelensis’ essential oil on a murine model. The essential oil was obtained by hydro-distillation, and the chemical analysis was performed by gas chromatography-mass spectrometry (GC-MS). In the murine model, wound-healing efficacy (WHE) and wound contraction (WC) were evaluated. Cytotoxic activity was evaluated in vitro using peritoneal macrophages from BALB/c mice. The results showed that 18 terpenoid-type compounds were identified in the essential oil. The essential oil had remarkable WHE regardless of the dose and accelerated WC and was not cytotoxic. In vitro tests with fibroblasts showed that cell viability was dose-dependent; by adding 1 mg/mL of essential oil (EO) to the culture medium, cell viability decreased below 80%, while, at doses of 0.1 and 0.01 mg/mL, it remained around 90%; thus, EO did not intervene in fibroblast proliferation, but it did influence fibroblast migration when wound-like was done in monolayer cultures. The results of this study demonstrated that the essential oil was a pro-wound-healing agent because it had good healing effectiveness with scars with good tensile strength and accelerated repair. The probable mechanism of action of the EO of B. morelensis, during the healing process, is the promotion of the migration of fibroblasts to the site of the wound, making them active in the production of collagen and promoting the remodeling of this collagen.

Platelet-Rich Plasma (PRP) Promotes Fetal Mesenchymal Stem/Stromal Cell Migration and Wound Healing Process

2014 ◽  
Vol 10 (3) ◽  
pp. 417-428 ◽  
Author(s):  
Maria G. Roubelakis ◽  
Ourania Trohatou ◽  
Apostolos Roubelakis ◽  
Evgenia Mili ◽  
Ioannis Kalaitzopoulos ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Stromal Cell ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Wound Healing Process

scholarly journals Stromal vascular fraction promotes migration of fibroblasts and angiogenesis through regulation of extracellular matrix in the skin wound healing process

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hongsen Bi ◽  
Hui Li ◽  
Chen Zhang ◽  
Yiqing Mao ◽  
Fangfei Nie ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Healing Process ◽  
Stromal Vascular Fraction ◽  
Wound Healing Process ◽  
Matrix Remodeling ◽  
Skin Defect ◽  
The Impact

Abstract Background A refractory wound is a typical complication of diabetes and is a common outcome after surgery. Current approaches have difficulty in improving wound healing. Recently, non-expanded stromal vascular fraction (SVF), which is derived from mature fat, has opened up new directions for the treatment of refractory wound healing. The aim of the current study is to systematically investigate the impact of SVF on wound healing, including the rate and characteristics of wound healing, ability of fibroblasts to migrate, and blood transport reconstruction, with a special emphasis on their precise molecular mechanisms. Methods SVF was isolated by digestion, followed by filtration and centrifugation, and then validated by immunocytochemistry, a MTS proliferation assay and multilineage potential analysis. A wound model was generated by creating 6-mm-diameter wounds, which include a full skin defect, on the backs of streptozocin-induced hyperglycemic mice. SVF or human adipose-derived stem cell (hADSC) suspensions were subcutaneously injected, and the wounds were characterized over a 9-day period by photography and measurements. A scratch test was used to determine whether changes in the migratory ability of fibroblasts occurred after co-culture with hADSCs. Angiogenesis was observed with human umbilical vein endothelial cells. mRNA from fibroblasts, endotheliocyte, and skin tissue were sequenced by high-throughput RNAseq, and differentially expressed genes, and pathways, potentially regulated by SVF or hADSCs were bioinformatically analyzed. Results Our data show that hADSCs have multiple characteristics of MSC. SVF and hADSCs significantly improved wound healing in hyperglycemic mice. hADSCs improve the migratory ability of fibroblasts and capillary structure formation in HUVECs. SVF promotes wound healing by focusing on angiogenesis and matrix remodeling. Conclusions Both SVF and hADSCs improve the function of fibroblast and endothelial cells, regulate gene expression, and promote skin healing. Various mechanisms likely are involved, including migration of fibroblasts, tubulogenesis of endothelial cells through regulation of cell adhesion, and cytokine pathways.

scholarly journals The Effect of a Triple Combination of Bevacizumab, Sodium Hyaluronate and a Collagen Matrix Implant in a Trabeculectomy Animal Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 896
Author(s):  
Vanessa Andrés-Guerrero ◽  
Irene Camacho-Bosca ◽  
Liseth Salazar-Quiñones ◽  
Nestor Ventura-Abreu ◽  
Mercedes Molero-Senosiain ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Rabbit Model ◽  
Sodium Hyaluronate ◽  
Collagen Matrix ◽  
New Combination ◽  
Wound Healing Process ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Fibroblast Migration

Currently available anti-scarring treatments for glaucoma filtration surgery (GFS) have potentially blinding complications, so there is a need for alternative and safer agents. The effects of the intrableb administration of a new combination of the anti-VEGF bevacizumab, sodium hyaluronate and a collagen matrix implant were investigated in a rabbit model of GFS, with the purpose of modulating inflammation, angiogenesis, fibroblast migration and fibrogenesis in the wound healing process. A comparative-effectiveness study was performed with twenty-four rabbits, randomly assigned to the following treatments: (a) biodegradable collagen matrix implant (Olo), (b) bevacizumab-loaded collagen matrix implant (Olo-BVZ), (c) bevacizumab-loaded collagen matrix implant combined with sodium hyaluronate (Olo-BVZ-H5) and (d) sham-operated animals (control). Rabbits underwent a conventional trabeculectomy and were studied over 30 days in terms of intraocular pressure and bleb characterization (height, area and vascularity in central, peripheral and non-bleb zones). Histologic differences among groups were further evaluated at day 30 (inflammation, total cellularity and degree of fibrosis in the area of surgery). Local delivery of bevacizumab (Olo-BVZ and Olo-BVZ-H5) increased the survival of the filtering bleb by 21% and 31%, respectively, and generated a significant decrease in inflammation and cell infiltration histologically 30 days after surgery, without exhibiting any local toxic effects. Olo-BVZ-H5 showed less lymphocyte infiltration and inflammation than the rest of the treatments. Intraoperative intrableb implantation of bevacizumab, sodium hyaluronate and a collagen matrix may provide an improved trabeculectomy outcome in this model of intense wound healing. This study showed an effective procedure with few surgical complications and a novel combination of active compounds that offer new possibilities to improve the efficacy of filtration surgery.

scholarly journals Directional Cell Migration and Chemotaxis in Wound Healing Response to PDGF-AA are Coordinated by the Primary Cilium in Fibroblasts

2010 ◽  
Vol 25 (2-3) ◽  
pp. 279-292 ◽  
Author(s):  
Linda Schneider ◽  
Michael Cammer ◽  
Jonathan Lehman ◽  
Sonja Nielsen ◽  
Charles Guerra ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Primary Cilium ◽  
Healing Response ◽  
Wound Healing Response ◽  
Directional Cell Migration

scholarly journals PCL/Mesoglycan Devices Obtained by Supercritical Foaming and Impregnation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 631 ◽  
Author(s):  
Paola Franco ◽  
Raffaella Belvedere ◽  
Emanuela Pessolano ◽  
Sara Liparoti ◽  
Roberto Pantani ◽  
...  
Keyword(s):  
Wound Healing ◽  
Biological Effects ◽  
Healing Process ◽  
Human Keratinocytes ◽  
Skin Lesions ◽  
Wound Healing Process ◽  
Process Conditions ◽  
Phosphate Buffered Saline

In this work, a one-shot process for the simultaneous foaming of polycaprolactone (PCL) and impregnation of mesoglycan (MSG) into the porous structure was successfully attempted. Supercritical carbon dioxide plays the role of the foaming agent with respect to PCL and of the solvent with respect to MSG. The main objective is to produce an innovative topical device for application on skin lesions, promoting prolonged pro-resolving effects. The obtained device offers a protective barrier to ensure a favorable and sterilized environment for the wound healing process. The impregnation kinetics revealed that a pressure of 17 MPa, a temperature of 35 °C, and a time of impregnation of 24 h assured a proper foaming of PCL in addition to the impregnation of the maximum amount of MSG; i.e., 0.22 mgMSG/mgPCL. After a preliminary study conducted on PCL granules used as brought, the MSG impregnation was performed at the optimized process conditions also on a PCL film, produced by compression molding, with the final goal of producing medical patches. Comparing the dissolution profiles in phosphate buffered saline solution (PBS) of pure MSG and MSG impregnated on foamed PCL, it was demonstrated that the release of MSG was significantly prolonged up to 70 times. Next, we performed functional assays of in vitro wound healing, cell invasion, and angiogenesis to evaluate the biological effects of the PCL-derived MSG. Interestingly, we found the ability of this composite system to promote the activation of human keratinocytes, fibroblasts, and endothelial cells, as the main actors of tissue regeneration, confirming what we previously showed for the MSG alone.

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