The Importance of Cutaneous Innervation in Wound Healing: From Animal Studies to Clinical Applications

Author(s):  
Shealinna Ge ◽  
Amor Khachemoune

The skin is a neuroimmunoendocrine organ that regularly undergoes injury and repair. The complex process of wound healing relies heavily on the cutaneous nervous system. Despite the observation that wound healing deficiencies cause significant morbidity and mortality for patients with nervous dysfunction across many disciplinaries, the role of cutaneous innervation in wound repair has not been well elucidated. In a previous article, we learned the basics of cutaneous neuroanatomy and the important neuropeptides involved in the wound healing process. Currently, we aim to synthesize the basics with observations from animal models and human studies for a more comprehensive understanding of nervous system involvement in cutaneous wound healing. We have demonstrated in this review, the importance of the cutaneous nervous system in each phase of wound healing through basic science research, animal experiments, and human studies.

Author(s):  
Shealinna Ge ◽  
Amor Khachemoune

Wound healing is an important topic in modern medicine across many disciplines. Healing of all cutaneous wounds, whether accidentally sustained or intentionally created, requires the common yet complex set of interactions between the immune, circulatory, nervous, endocrine, and integumentary systems. Deficits in any of these systems or the molecular factors that mediate their communications can contribute to impaired healing of cutaneous wounds. While the stages of wound repair, angiogenesis, growth factors, and cytokines involved have been extensively studied, the role of the cutaneous nervous system in wound healing has not been well outlined. We have provided a basic overview of cutaneous innervation and wound repair for the dermatologic surgeon by outlining the normal cutaneous nervous anatomy and function and discussing the most important neuropeptides that mediate the wound healing process.


Author(s):  
Ahmed G. Hegazi ◽  
Faiz M. Al Guthami ◽  
Mohamed H. Basiouny ◽  
Ahmed F.M. Al Gethami

Honey has been documented as the oldest traditional medicine. It has been effective in suppressing inflammation, wound repair enhancer, and rapid autolytic debridement. The aim of this investigation was to evaluate the role of Saudi Arabia Talh honey (Acacia nilotica) dressing as a good alternative in care of diabetic foot (DFU) healing activity for twenty patients, wound total bacterial count, and serum cytokines levels (IFN-γ, IL-1, and IL-6). The results showed that Talh honey stimulates the wound healing process, broad-spectrum antibacterial activity, and reduction in the proinflammatory cytokines IFN-γ, IL-1, and IL-6 levels. It could be concluded that Talh honey bioactivities enhance wound healing by promoting tissue growth leading to wound repair, antibacterial, and reduction of inflammation.


2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yan Xu ◽  
Ze Lin ◽  
Lei He ◽  
Yanzhen Qu ◽  
Liu Ouyang ◽  
...  

Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can improve wound repair outcomes by promoting such epithelial regeneration. Platelet-rich plasma (PRP) is known to facilitate enhanced wound healing, yet the mechanisms underlying its activity are poorly understood. To explore these mechanisms, we first isolated PRP-derived Exos (PRP-Exos). Using immortalized keratinocytes (HaCaT cells) treated with PBS, PRP, or PRP-Exos, we conducted a series of in vitro Cell Counting Kit-8 (CCK-8), EdU, scratch wound, and transwell assays. We then established a wound defect model in vivo in mice and assessed differences in the mRNA expression within these wounds to better understand the basis for PRP-mediated wound healing. The functions of PRP-Exos and USP15 in the context of wound healing were then confirmed through additional in vitro and in vivo experiments. We found that PRP-Exos effectively promoted the in vitro proliferation, migration, and wound healing activity of HaCaT cells. USP15 was further identified as a key mediator through which these PRP-Exos were able to promote tissue repair both in vitro and in vivo. At a mechanistic level, USP15 enhanced the functional properties of HaCaT cells by promoting EIF4A1 deubiquitination. Thus, PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.


2021 ◽  
Vol 8 (4) ◽  
pp. 279
Author(s):  
Bina Melvia Girsang ◽  
Eqlima Elfira ◽  
Farida Linda Sari Siregar

<em>Postpartum mothers with an indication of episiotomy will experience a higher level of pain. This birth canal trauma is acute and is expected to recover in a short period of time, can be measured, and without serious complications. The aim of this study was to identify the healing process of postpartum maternal perineal wounds. The intervention was carried out on 31 postpartum mothers with the selection using purposive sampling technique. Maternity cool gel pad (MCGP) which was applied to the perineal wound care intervention on the 2nd and 3rd day after delivery showed the wound healing process was observed using the REEDA measuring instrument and analyzed using the T one sample test. The repair of the wound repair scale from the mean REEDA score (10.81 ± 2.98) occurred in all wounds of the study respondents at post intervention (5.32 ± 1.73). Maternity cool gel pad intervention assisted the wound healing process in post intervention data (P &lt;0.005). The results of this study can be indicative of an inflammatory response locally in perineal wounds, but further research is needed to observe the impact of perineal wound healing with a combination of methods that can help evaluate the perineal wound repair process that can be done by mothers independently at home.</em>


2021 ◽  
Author(s):  
Huifang Ge ◽  
Yiqun Jiang ◽  
Zhenzhen Ning ◽  
Zhiqing Hu ◽  
Sitong Ma ◽  
...  

Recent studies have indicated that activity peptides can induce an improvement in wound repair. Herein, we evaluated egg white peptides (EWPs) as a nutrition supplement to improve skin mechanical damage...


2018 ◽  
Vol 19 (12) ◽  
pp. 3862 ◽  
Author(s):  
Junhe Shi ◽  
May Barakat ◽  
Dandan Chen ◽  
Lin Chen

Bicellular tight junctions (TJs) are intercellular junctions comprised of a variety of transmembrane proteins including occludin, claudins, and junctional adhesion molecules (JAMs) as well as intracellular scaffold proteins such as zonula occludens (ZOs). TJs are functional, intercellular structures that form a barrier between adjacent cells, which constantly seals and unseals to control the paracellular passage of molecules. They are primarily present in the epithelial and endothelial cells of all tissues and organs. In addition to their well-recognized roles in maintaining cell polarity and barrier functions, TJs are important regulators of signal transduction, which modulates cell proliferation, migration, and differentiation, as well as some components of the immune response and homeostasis. A vast breadth of research data is available on TJs, but little has been done to decipher their specific roles in wound healing, despite their primary distribution in epithelial and endothelial cells, which are essential contributors to the wound healing process. Some data exists to indicate that a better understanding of the functions and significance of TJs in healing wounds may prove crucial for future improvements in wound healing research and therapy. Specifically, recent studies demonstrate that occludin and claudin-1, which are two TJ component proteins, are present in migrating epithelial cells at the wound edge but are absent in chronic wounds. This indicates that functional TJs may be critical for effective wound healing. A tremendous amount of work is needed to investigate their roles in barrier function, re-epithelialization, angiogenesis, scar formation, and in the interactions between epithelial cells, endothelial cells, and immune cells both in the acute wound healing process and in non-healing wounds. A more thorough understanding of TJs in wound healing may shed new light on potential research targets and reveal novel strategies to enhance tissue regeneration and improve wound repair.


2014 ◽  
Vol 25 (6) ◽  
pp. 776-790 ◽  
Author(s):  
A. S. Menko ◽  
B. M. Bleaken ◽  
A. A. Libowitz ◽  
L. Zhang ◽  
M. A. Stepp ◽  
...  

Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by an innate mesenchymal subpopulation of vimentin-rich repair cells. We report that vimentin is essential to the function of repair cells as the directors of the wound-healing process. Vimentin and not actin filaments are the predominant cytoskeletal elements in the lamellipodial extensions of the repair cells at the wound edge. These vimentin filaments link to paxillin-containing focal adhesions at the lamellipodial tips. Microtubules are involved in the extension of vimentin filaments in repair cells, the elaboration of vimentin-rich protrusions, and wound closure. The requirement for vimentin in repair cell function is revealed by both small interfering RNA vimentin knockdown and exposure to the vimentin-targeted drug withaferin A. Perturbation of vimentin impairs repair cell function and wound closure. Coimmunoprecipitation analysis reveals for the first time that myosin IIB is associated with vimentin, linking vimentin function in cell migration to myosin II motor proteins. These studies reveal a critical role for vimentin in repair cell function in regulating the collective movement of the epithelium in response to wounding.


2012 ◽  
Vol 302 (8) ◽  
pp. C1213-C1225 ◽  
Author(s):  
Chen Zhang ◽  
Chek Kun Tan ◽  
Craig McFarlane ◽  
Mridula Sharma ◽  
Nguan Soon Tan ◽  
...  

Myostatin (Mstn) is a secreted growth and differentiation factor that belongs to the transforming growth factor-β (TGF-β) superfamily. Mstn has been well characterized as a regulator of myogenesis and has been shown to play a critical role in postnatal muscle regeneration. Herein, we report for the first time that Mstn is expressed in both epidermis and dermis of murine and human skin and that Mstn-null mice exhibited delayed skin wound healing attributable to a combination of effects resulting from delayed epidermal reepithelialization and dermal contraction. In epidermis, reduced keratinocyte migration and protracted keratinocyte proliferation were observed, which subsequently led to delayed recovery of epidermal thickness and slower reepithelialization. Furthermore, primary keratinocytes derived from Mstn-null mice displayed reduced migration capacity and increased proliferation rate as assessed through in vitro migration and adhesion assays, as well as bromodeoxyuridine incorporation and Western blot analysis. Moreover, in dermis, both fibroblast-to-myofibroblast transformation and collagen deposition were concomitantly reduced, resulting in a delayed dermal wound contraction. These decreases are due to the inhibition of TGF-β signaling. In agreement, the expression of decorin, a naturally occurring TGF-β suppressor, was elevated in Mstn-null mice; moreover, topical treatment with TGF-β1 protein rescued the impaired skin wound healing observed in Mstn-null mice. These observations highlight the interplay between TGF-β and Mstn signaling pathways, specifically through Mstn regulation of decorin levels during the skin wound healing process. Thus we propose that Mstn agonists might be beneficial for skin wound repair.


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