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 ◽  
...  

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.

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3053-3060 ◽  
Author(s):  
Maureane Hoffman ◽  
Anna Harger ◽  
Angela Lenkowski ◽  
Ulla Hedner ◽  
Harold R. Roberts ◽  
...  

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.


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

2013 ◽  
Vol 133 (10) ◽  
pp. 2461-2470 ◽  
Author(s):  
Laura Campbell ◽  
Charis R. Saville ◽  
Peter J. Murray ◽  
Sheena M. Cruickshank ◽  
Matthew J. Hardman

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.


2008 ◽  
Vol 11 (02) ◽  
pp. 63-69 ◽  
Author(s):  
Manabu Taguchi ◽  
Steven L. Moran ◽  
Mark E. Zobitz ◽  
Chunfeng Zhao ◽  
Malayannan Subramaniam ◽  
...  

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.


2008 ◽  
Vol 109 (1) ◽  
pp. 130-136 ◽  
Author(s):  
Jerri M. Rook ◽  
Wohaib Hasan ◽  
Kenneth E. McCarson

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.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Giles T. S. Kirby ◽  
Stuart J. Mills ◽  
Allison J. Cowin ◽  
Louise E. Smith

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.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Suman Kanji ◽  
Hiranmoy Das

Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process.


Nanoscale ◽  
2021 ◽  
Author(s):  
Kuo Li ◽  
Dan Li ◽  
Cheng-Hsuan Li ◽  
pengfei Zhuang ◽  
Chunmei Dai ◽  
...  

The wound healing process involves multiple steps including hemostasis, inflammation, proliferation, and tissue remodeling. Nanomaterials have been employed externally for healing wounds. However, their use as systemic therapeutics has not...


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