scholarly journals Temporal Effects of Topical Morphine Application on Cutaneous Wound Healing

2008 ◽  
Vol 109 (1) ◽  
pp. 130-136 ◽  
Author(s):  
Jerri M. Rook ◽  
Wohaib Hasan ◽  
Kenneth E. McCarson
Keyword(s):  
Wound Healing ◽  
Time Course ◽  
Wound Closure ◽  
Healing Process ◽  
Topical Administration ◽  
Scar Tissue ◽  
Skin Thickness ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Opioid Administration

Background Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat. Methods Full-thickness 4-mm-diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mm morphine sulfate on days 0-3 or 4-10 postwounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 postwounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin. Results Delays in wound closure observed during morphine application on days 0-3 postwounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 postwounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. In addition, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin. Conclusions These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds.

Mechanical unloading impairs keratinocyte migration and angiogenesis during cutaneous wound healing

2008 ◽  
Vol 104 (5) ◽  
pp. 1295-1303 ◽  
Author(s):  
Katherine A. Radek ◽  
Lisa A. Baer ◽  
Jennifer Eckhardt ◽  
Luisa A. DiPietro ◽  
Charles E. Wade
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Closure ◽  
Healing Process ◽  
Bed Rest ◽  
Collagen Content ◽  
Cutaneous Wound Healing ◽  
Endothelial Cell Function ◽  
Cutaneous Wound ◽  
Mechanical Unloading

Although initially thought to improve an individual's ability to heal, mechanical unloading promoted by extended periods of bed rest has emerged as a contributing factor to delayed or aberrant tissue repair. Using a rat hindlimb unloading (HLU) model of hypogravity, we mimicked some aspects of physical inactivity by removing weight-bearing loads from the hindlimbs and producing a systemic cephalic fluid shift. This model simulates bed rest in that the animal undergoes physiological adaptations, resulting in a reduction in exercise capability, increased frequency of orthostatic intolerance, and a reduction in plasma volume. To investigate whether changes associated with prior prolonged bed rest correlate with impaired cutaneous wound healing, we examined wound closure, angiogenesis, and collagen content in day 2 to day 21 wounds from rats exposed to HLU 2 wk before excisional wounding. Wound closure was delayed in day 2 wounds from HLU rats compared with ambulatory controls. Although the levels of proangiogenic growth factors, fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor (VEGF) were similar between the two groups, wound vascularity was significantly reduced in day 7 wounds from HLU animals. To further examine this disparity, total collagen content was assessed but found to be similar between the two groups. Taken together, these results suggest that keratinocyte and endothelial cell function may be impaired during the wound healing process under periods of prolonged inactivity or bed rest.

Cutaneous wound healing is impaired in hemophilia B

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3053-3060 ◽  
Author(s):  
Maureane Hoffman ◽  
Anna Harger ◽  
Angela Lenkowski ◽  
Ulla Hedner ◽  
Harold R. Roberts ◽  
...  
Keyword(s):  
Wound Healing ◽  
Time Course ◽  
Ferric Iron ◽  
Hemophilia B ◽  
Cutaneous Wound Healing ◽  
Delayed Wound Healing ◽  
Cutaneous Wound ◽  
Time Points ◽  
Hemophilic Arthropathy ◽  
Healing Wounds

Abstract We used a mouse model to test the hypothesis that the time course and histology of wound healing is altered in hemophilia B. Punch biopsies (3 mm) were placed in the skin of normal mice and mice with hemophilia. The size of the wounds was measured daily until the epidermal defect closed. All wounds closed in mice with hemophilia by 12 days, compared with 10 days in normal animals. Skin from the area of the wound was harvested at different time points and examined histologically. Hemophilic animals developed subcutaneous hematomas; normal animals did not. Macrophage infiltration was significantly delayed in hemophilia B. Unexpectedly, hemophilic mice developed twice as many blood vessels in the healing wounds as controls, and the increased vascularity persisted for at least 2 weeks. The deposition and persistence of ferric iron was also greater in hemophilic mice. We hypothesize that iron plays a role in promoting excess angiogenesis after wounding as it had been proposed to do in hemophilic arthropathy. We have demonstrated that impaired coagulation leads to delayed wound healing with abnormal histology. Our findings have significant implications for treatment of patients with hemophilia, and also highlight the importance of rapidly establishing hemostasis following trauma or surgery.

Influence of sensory neuropeptides on human cutaneous wound healing process

2014 ◽  
Vol 74 (3) ◽  
pp. 193-203 ◽  
Author(s):  
J. Chéret ◽  
N. Lebonvallet ◽  
V. Buhé ◽  
J.L. Carre ◽  
L. Misery ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wound Healing Process ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Sensory Neuropeptides

scholarly journals Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Na-Young Park ◽  
Giuseppe Valacchi ◽  
Yunsook Lim
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Wound Closure ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Anti Inflammatory

Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA), a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage). We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

scholarly journals Collagen extract obtained from Nile tilapia (Oreochromis niloticus L.) skin accelerates wound healing in rat model via up regulating VEGF, bFGF, and α-SMA genes expression

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Zizy I. Elbialy ◽  
Ayman Atiba ◽  
Aml Abdelnaby ◽  
Ibrahim I. Al-Hawary ◽  
Ahmed Elsheshtawy ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Rat Model ◽  
Nile Tilapia ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Control Group ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Genes Expression

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.

scholarly journals Recombinant Myxoma Virus-Derived Immune Modulator M-T7 Accelerates Cutaneous Wound Healing and Improves Tissue Remodeling

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1003
Author(s):  
Jordan R. Yaron ◽  
Liqiang Zhang ◽  
Qiuyun Guo ◽  
Enkidia A. Awo ◽  
Michelle Burgin ◽  
...  
Keyword(s):  
Wound Healing ◽  
Topical Treatment ◽  
Immune Cell ◽  
Healing Process ◽  
Tissue Remodeling ◽  
Myxoma Virus ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Arginase 1 ◽  
Healing Wounds

Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or “fine tune” the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.

scholarly journals Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
Author(s):  
Sungjoo Park ◽  
Eunsu Ko ◽  
Jun Hyoung Lee ◽  
Yoseb Song ◽  
Chang-Hao Cui ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Connective Tissue ◽  
Wound Closure ◽  
Tissue Growth ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
And Migration ◽  
Proliferation And Migration

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

scholarly journals WOUND-HEALING PROPERTIES OF TRANSFORMING GROWTH FACTOR β (TGF-β) INDUCIBLE EARLY GENE 1 (TIEG1) KNOCKOUT MICE

2008 ◽  
Vol 11 (02) ◽  
pp. 63-69 ◽  
Author(s):  
Manabu Taguchi ◽  
Steven L. Moran ◽  
Mark E. Zobitz ◽  
Chunfeng Zhao ◽  
Malayannan Subramaniam ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Knockout Mice ◽  
Transforming Growth Factor ◽  
Breaking Strength ◽  
Healing Process ◽  
Early Gene ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Transforming growth factor beta (TGF-β) has a broad effect on wound healing, but many questions remain about the regulation of TGF-β during the healing process. TGF-β inducible early gene 1 (TIEG1) is a primary response gene for TGF-β that controls the activities of the TGF-β/Smad pathway, the primary TGF-β signaling pathway. The purpose of this study was to investigate the role of TIEG1 in cutaneous wound healing using TIEG1 knockout mice. The wound healing in TIEG1 knockout mice and wild-type controls was evaluated by wound breaking strength, Western blot, and histology at postoperative days 3, 7, and 14. Although re-epithelialization of both groups was similarly complete at day 7, the TIEG1 knockout mice had a significantly lower wound breaking strength than the controls at postoperative day 14. These results suggest that TIEG1 expression may be an important factor involved in the initiation and support of normal cutaneous wound healing.

scholarly journals Stem Cells for Cutaneous Wound Healing

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Giles T. S. Kirby ◽  
Stuart J. Mills ◽  
Allison J. Cowin ◽  
Louise E. Smith
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Chronic Wounds ◽  
Healing Process ◽  
Clinical Use ◽  
Cutaneous Wound Healing ◽  
Cell Therapies ◽  
Cutaneous Wound ◽  
Matrix Deposition ◽  
Obesity And Diabetes

Optimum healing of a cutaneous wound involves a well-orchestrated cascade of biological and molecular processes involving cell migration, proliferation, extracellular matrix deposition, and remodelling. When the normal biological process fails for any reason, this healing process can stall resulting in chronic wounds. Wounds are a growing clinical burden on healthcare systems and with an aging population as well as increasing incidences of obesity and diabetes, this problem is set to increase. Cell therapies may be the solution. A range of cell based approaches have begun to cross the rift from bench to bedside and the supporting data suggests that the appropriate administration of stem cells can accelerate wound healing. This review examines the main cell types explored for cutaneous wound healing with a focus on clinical use. The literature overwhelmingly suggests that cell therapies can help to heal cutaneous wounds when used appropriately but we are at risk of clinical use outpacing the evidence. There is a need, now more than ever, for standardised methods of cell characterisation and delivery, as well as randomised clinical trials.

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