scholarly journals NGF Accelerates Cutaneous Wound Healing by Promoting the Migration of Dermal Fibroblasts via the PI3K/Akt-Rac1-JNK and ERK Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Ji-Cai Chen ◽  
Bei-Bei Lin ◽  
Hou-Wen Hu ◽  
Cai Lin ◽  
Wen-Yang Jin ◽  
...  

As a well-known neurotrophic factor, nerve growth factor (NGF) has also been extensively recognized for its acceleration of healing in cutaneous wounds in both animal models and randomized clinical trials. However, the underlying mechanisms accounting for the therapeutic effect of NGF on skin wounds are not fully understood. NGF treatment significantly accelerated the rate of wound healing by promoting wound reepithelialization, the formation of granulation tissue, and collagen production. To explore the possible mechanisms of this process, the expression levels of CD68, VEGF, PCNA, and TGF-β1 in wounds were detected by immunohistochemical staining. The levels of these proteins were all significantly raised in NGF-treated wounds compared to untreated controls. NGF also significantly promoted the migration, but not the proliferation, of dermal fibroblasts. NGF induced a remarkable increase in the activity of PI3K/Akt, JNK, ERK, and Rac1, and blockade with their specific inhibitors significantly impaired the NGF-induced migration. In conclusion, NGF significantly accelerated the healing of skin excisional wounds in rats and the fibroblast migration induced by NGF may contribute to this healing process. The activation of PI3K/Akt, Rac1, JNK, and ERK were all involved in the regulation of NGF-induced fibroblast migration.

2021 ◽  
Vol 22 (12) ◽  
pp. 6486
Author(s):  
Thayaalini Subramaniam ◽  
Mh Busra Fauzi ◽  
Yogeswaran Lokanathan ◽  
Jia Xian Law

Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings.


2005 ◽  
Vol 53 (5) ◽  
pp. 571-581 ◽  
Author(s):  
Pauli A. Puolakkainen ◽  
Amy D. Bradshaw ◽  
Rolf A. Brekken ◽  
May J. Reed ◽  
Themis Kyriakides ◽  
...  

Secreted protein acidic and rich in cysteine (SPARC) and thrombospondin-2 (TSP-2) are structurally unrelated matricellular proteins that have important roles in cell- extracellular matrix (ECM) interactions and tissue repair. SPARC-null mice exhibit accelerated wound closure, and TSP-2-null mice show an overall enhancement in wound healing. To assess potential compensation of one protein for the other, we examined cutaneous wound healing and fibrovascular invasion of subcutaneous sponges in SPARC-TSP-2 (ST) double-null and wild-type (WT) mice. Epidermal closure of cutaneous wounds was found to occur significantly faster in ST-double-null mice, compared with WT animals: histological analysis of dermal wound repair revealed significantly more mature phases of healing at 1, 4, 7, 10, and 14 days after wounding, and electron microscopy showed disrupted ECM at 14 days in these mice. ST-double-null dermal fibroblasts displayed accelerated migration, relative to WT fibroblasts, in a wounding assay in vitro, as well as enhanced contraction of native collagen gels. Zymography indicated that fibroblasts from ST-double-null mice also produced higher levels of matrix metalloproteinase (MMP)-2. These data are consistent with the increased fibrovascular invasion of subcutaneous sponge implants seen in the double-null mice. The generally accelerated wound healing of ST-double-null mice reflects that described for the single-null animals. Importantly, the absence of both proteins results in elevated MMP-2 levels. SPARC and TSP-2 therefore perform similar functions in the regulation of cutaneous wound healing, but fine-tuning with respect to ECM production and remodeling could account for the enhanced response seen in ST-double-null mice.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pooya Ebrahimi ◽  
Mahdi Hadilou ◽  
Ferdos Naserneysari ◽  
Amirmohammad Dolatabadi ◽  
Rana Tarzemany ◽  
...  

Abstract Background Photobiomodulation is widely being used to improve the wound healing process in dentistry and a vast majority of studies have proven its benefits. But there are plenty of knowledge gaps according to the optimal laser characteristics which should be used to maximize the healing effects of lasers. The goal of this systematic review and meta-analysis was to determine the effect of photobiomodulation (PBM) as an adjunctive treatment to periodontal therapies to evaluate secondary intention gingival wound healing and post-operative pain. Methods Five databases (PubMed, Embase, Scopus, ProQuest, and Web of Sciences) were searched up to November 30, 2020, for clinical trials that reported the result of the application of PBM on secondary gingival healing wounds and post-operative pain and discomfort after periodontal surgeries. Two independent reviewers selected the eligible studies and the outcomes of interest were extracted. The quality of eligible studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Results Ultimately, twelve studies were included in this review. The application of PBM as an adjunct to periodontal surgeries resulted in a significant improvement in wound healing indices. The Landry wound healing index at the 7th post-operative day was significantly improved (SMD = 1.044 [95% CI 0.62–1.46]; p < 0.01) in PBM + surgery groups compared to the control groups. There was also a statistically significant increase in the complete wound epithelialization (RR = 3.23 [95% CI 1.66–6.31]; p < 0.01) at the 14th post-operative day compared to the control groups. The methods used to assess the post-operative pain were heterogeneous, and therefore the results were limited which made the meta-analysis for post-operative pain assessment not possible. Conclusion Based on the results of this review, PBM can be effectively used as a method to improve secondary intention wound healing. High-quality randomized clinical trials, however, are needed in the future to identify the optimal PBM irradiation parameters and the effect of PBM on post-operative pain.


2021 ◽  
Vol 14 (4) ◽  
pp. 301
Author(s):  
Yayoi Kawano ◽  
Viorica Patrulea ◽  
Emmanuelle Sublet ◽  
Gerrit Borchard ◽  
Takuya Iyoda ◽  
...  

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.


2021 ◽  
pp. 1-13
Author(s):  
Eduardo Anitua ◽  
Victoria Muñoz ◽  
Libe Aspe ◽  
Roberto Tierno ◽  
Adrian García-Salvador ◽  
...  

<b><i>Introduction:</i></b> Skin injury and wound healing is an inevitable event during lifetime. However, several complications may hamper the regeneration of the cutaneous tissue and lead to a chronic profile that prolongs patient recovery. Platelet-rich plasma is rising as an effective and safe alternative to the management of wounds. However, this technology presents some limitations such as the need for repeated blood extractions and health-care interventions. <b><i>Objective:</i></b> The aim of this study was to assess the use of an endogenous and storable topical serum (ES) derived from plasma rich in growth factors promoting wound healing, and to obtain preliminary data regarding its clinical and experimental effect over ulcerated skin models and patient care. <b><i>Methods:</i></b> Human dermal fibroblast and 3D organotypic ulcerated skin models were used to assess ES over the main mechanisms of wound healing including cell migration, edge contraction, collagen synthesis, tissue damage, extracellular matrix remodeling, cell death, metabolic activity, and histomorphometry analysis. Additionally, 4 patients suffering from skin wounds were treated and clinically assessed. <b><i>Results:</i></b> ES promoted dermal fibroblast migration, wound edge contraction, and collagen synthesis. When topically applied, ES increased collagen and elastin deposition and reduced tissue damage. The interstitial edema, structural integrity, and cell activity were also maintained, and apoptotic levels were reduced. Patients suffering from hard-to-heal wounds of different etiologies were treated with ES, and the ulcers healed completely within few weeks with no reported adverse events. <b><i>Conclusion:</i></b> This preliminary study suggests that ES might promote cutaneous wound healing and may be useful for accelerating the re-epithelization of skin ulcers.


2014 ◽  
Vol 74 (3) ◽  
pp. 193-203 ◽  
Author(s):  
J. Chéret ◽  
N. Lebonvallet ◽  
V. Buhé ◽  
J.L. Carre ◽  
L. Misery ◽  
...  

2018 ◽  
Vol 32 (8) ◽  
pp. 1011-1023 ◽  
Author(s):  
Ji-Ung Park ◽  
Seol-Ha Jeong ◽  
Eun-Ho Song ◽  
Juha Song ◽  
Hyoun-Ee Kim ◽  
...  

In this study, we evaluated the surface characterization of a novel chitosan–silica hybridized membrane and highlighted the substantial role of silica in the wound environment. The chemical coupling of chitosan and silica resulted in a more condensed network compared with pure chitosan, which was eventually able to stably maintain its framework, particularly in the wet state. In addition, we closely observed the wound-healing process along with the surface interaction between chitosan–silica and the wound site using large-surface-area wounds in a porcine model. Our evidence indicates that chitosan–silica exerts a synergetic effect of both materials to promote a remarkable wound-healing process. In particular, the silica in chitosan–silica accelerated wound closure including wound contraction, and re-epithelialization via enhancement of cell recruitment, epidermal maturity, neovascularization, and granulation tissue formation compared with pure chitosan and other commercial dressing materials. This advanced wound dressing material may lead to effective treatment for problematic cutaneous wounds and can be further applied for human skin regeneration.


2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Zizy I. Elbialy ◽  
Ayman Atiba ◽  
Aml Abdelnaby ◽  
Ibrahim I. Al-Hawary ◽  
Ahmed Elsheshtawy ◽  
...  

Abstract Background Collagen is the most abundant structural protein in the mammalian connective tissue and represents approximately 30% of animal protein. The current study evaluated the potential capacity of collagen extract derived from Nile tilapia skin in improving the cutaneous wound healing in rats and investigated the underlying possible mechanisms. A rat model was used, and the experimental design included a control group (CG) and the tilapia collagen treated group (TCG). Full-thickness wounds were conducted on the back of all the rats under general anesthesia, then the tilapia collagen extract was applied topically on the wound area of TCG. Wound areas of the two experimental groups were measured on days 0, 3, 6, 9, 12, and 15 post-wounding. The stages of the wound granulation tissues were detected by histopathologic examination and the expression of vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-ß1) were investigated using immunohistochemistry. Moreover, relative gene expression analysis of transforming growth factor-beta (TGF-ß1), basic fibroblast growth factor (bFGF), and alpha-smooth muscle actin (α-SMA) were quantified by real-time qPCR. Results The histopathological assessment showed noticeable signs of skin healing in TCG compared to CG. Immunohistochemistry results revealed remarkable enhancement in the expression levels of VEGF and TGF-β1 in TCG. Furthermore, TCG exhibited marked upregulation in the VEGF, bFGF, and α-SMA genes expression. These findings suggested that the topical application of Nile tilapia collagen extract can promote the cutaneous wound healing process in rats, which could be attributed to its stimulating effect on recruiting and activating macrophages to produce chemotactic growth factors, fibroblast proliferation, and angiogenesis. Conclusions The collagen extract could, therefore, be a potential biomaterial for cutaneous wound healing therapeutics.


1999 ◽  
Vol 69 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Weimann ◽  
Hermann

The effect of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts from three different donors was investigated. The migration of cells into a wounded area was dose-dependently stimulated by Ca D-pantothenate. The number of cells that migrated across the edge of the wound increased from 32 ± 7 cells/ mm without Ca D-pantothenate to 76 ± 2 cells/ mm with 100 mg/ml Ca D-pantothenate. Moreover, the mean migration distance per cell increased from 0.23 ± 0.05 mm to 0.33 ± 0.02 mm. The mean migration speed was calculated to be 10.5 mm/hour without and 15 mm/hour with Ca D-pantothenate. Cell proliferation was also dose-dependently stimulated. The final cell densities were 1.2 to 1.6-fold higher in cultures containing 100 mg/ml Ca D-pantothenate. The protein synthesis was modulated, since two unidentified proteins were more strongly expressed in pantothenate supplemented cultures. In conclusion, Ca D-pantothenate accelerates the wound healing process by increasing the number of migrating cells, their distance and hence their speed. In addition, cell division is increased and the protein synthesis changed. These results suggest that higher quantities of pantothenate are locally required to enhance wound healing.


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