These scars generally fade as well as flatten to the surrounding skin level. The first step toward treatment of excessive scarring is early recognition and institution of therapy after surgery or trauma. Meticulous tissue handling, suturing, and wound management with efforts to prevent infection are mandatory [ 72 ].
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Sun protection to reduce scar hyperpigmentation is essential. Patients who are at increased risk of excessive scarring benefit from preventive techniques, which include silicone gel sheeting or ointments, hypoallergenic microporous tape, and concurrent intralesional steroid injection [ 72 , 73 ]. Silicone gel sheeting is widely used for hypertrophic scar treatment and the only remedy with high evidence [ 74 ]. Silicone gel sheeting has a plus-year history with several randomized controlled trials that support its safe and effective use [ 73 , 75 ].
Proposed mechanisms of action for scar reduction include improved hydration and occlusion, increased temperature and change in scar mechanical tension.
A great deal of research is focused on the development of treatment strategies to reduce or prevent scarring. Lately, tissue mechanics, duration of wound closure and intensity of the inflammatory reaction have come more into focus to address excessive scarring. Clinical phase II and III trials are currently performed using several novel drugs to tackle fibrotic diseases [ 77 ]. Surprisingly, systemic treatment with leukotriene receptor antagonists, angiotensin-converting enzyme, calcium antagonists or statins for asthma, hypertension or hypercholesterinemia, respectively, coincided with reduced scarring [ 78 ].
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These incidental effects could be, in part, reproduced in animal models [ 79 ]. Hopefully, on-going clinical studies will yield sufficient and convincing results for future treatment of excessive scarring. Currently, the surgical state of the art for the covering of wounds displays autologous skin grafting, which is, however, limited by the availability of autologous skin. Even though the plastic surgical armamentarium comprises a diverse spectrum for tissue transfer, the efforts do not resemble true tissue regeneration or replacements yet.
Tissue engineering seeks to create replacement tissues to restore or maintain organ function and to repair tissue defects [ 40 ].
Recreating an environment that promotes fundamental homeostatic mechanisms is a significant challenge in tissue engineering [ 80 ]. Optimizing cell survival, proliferation, differentiation, apoptosis and angiogenesis and provide suitable stromal support and signaling clues are the key to successfully generating clinically useful tissue [ 81 ]. The increasing knowledge of molecular and cellular mechanisms and lessons learned through frustrated attempts enables us to better define future directions, taking into account the various underlying pathophysiological conditions and differing wound types and their specific requirements.
Independent of the tissue engineering product, a meticulous wound bed preparation, minimizing bacterial burden, thorough debridement of nonviable tissue, control of edema, optimizing the vascular status to allow for optimal nutrient supply, prevent additional trauma and reduction of mechanical stress are fundamental prerequisites for successful wound healing.
Various tissue engineering approaches ranging from temporary wound dressings to improve wound milieu to acellular scaffolds to cell transplants and dermal substitutes are being investigated focusing on many different growth factors, as already mentioned above. Yet the orchestra of growth factors is numerous and the timely interaction is not completely explored, hence further research is needed to provide the appropriate cell signaling clues to promote true wound regeneration.
Another widely studied aspect is the field of matrix materials and scaffolds to provide structural support and promote cell migration. Furthermore, decellularization of allogenic or xenogenic skin, 3D printing and currently genetic modifications of the wound bed offer new perspectives [ 40 , 87 ]. In addition, cell transplantation either incorporated in the matrix material or implanted in the wound bed has gained recent interest.
Stem and progenitor cells originally thought to replace organ-specific cells have recently been discovered to also deploy their potential for wound healing through chemotaxis of host cells and as a source for cell signaling molecules. However, none of the above-mentioned research work has found its way to standardized clinical application yet [ 40 ]. In summary, an optimal dermal substitute or skin replacement therapy has not been found yet by means of tissue engineering.
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With increasing knowledge about cellular interaction and cell signaling as well as the pathophysiological requirements of specific wound conditions, tissue engineering holds great perspectives for the future to enhance wound healing. Plasma is a well-known phenomenon in daily life. In physics, plasma is a particle mixture at the atomic-molecular level, the components of which are partially charged components, ions, and electrons.
This means that plasma contains free charge carriers. In addition to the 3 classical aggregate states solid, liquid, gaseous , plasma is considered a further state of matter. A characteristic of plasma, which is essential for its behavior, but also for technical use, is, therefore, its electrical conductivity. On earth, there are natural plasmas in the ionosphere and lightning. In the biosphere, there are no practically usable natural plasmas. Therefore, plasma must be generated in order to be able to apply it technically.
This is usually done by gas discharge. Neon tubes, plasma TVs and nuclear fusion are examples of regular application of plasma technique. In medical engineering, plasma already has a wide spectrum of use, e. After years of technological progress, plasma is now ready for medical application. That means, electric currents and temperature are now tolerable for medical application in vivo Fig. The functional principle is the electric stimulation of argon gas that produces a plasma flame with tolerable temperatures and currencies Fig. Different studies gave evidence of the successful decontamination of multidrug-resistant, contaminated wounds through nonthermal plasma NTP or cold atmospheric plasma CAP [ 88 , 89 , 90 ].
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A secondary beneficial feature of plasma derives from its genomic effects [ 91 ]. To examine wound healing activity of an atmospheric pressure plasma jet in vivo aside from decontamination effects, Schmidt et al.
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Herein, the study could show significantly accelerated wound reepithelialization from day 3 to 9 compared to untreated controls. This was further underscored by in vitro studies, showing enhanced migratory behavior of keratinocytes and fibroblasts. Gap closure in wound scratch assays was significantly accelerated in CAP-treated cells [ 92 ].
Keratinocytes mainly regenerate the epidermis and play an important role in wound closure. Daily short plasma applications up to 40 s to murine superficial skin wounds showed significantly increased epidermal cell regeneration, granulation tissue hyperplasia, and collagen deposition [ 93 ]. This was also confirmed by plasma application on human skin biopsies where short CAP exposure min was already able to induce the proliferation of keratinocytes [ 94 ].
Concomitantly, longer exposures might lead to overdosing of the plasma application inducing apoptotic cell death with a further disturbed wound healing process [ 93 , 94 ]. Chernets et al. Single treatment of in vitro organ culture systems with NTP was already able to enhance the survival, growth, and elongation of mouse limb autopods. Perceptible transformations comprised an improved development of the digit length as well as the definition of digit separation [ 95 ].
In our own group, we have treated cultivated fibrocytes with NTP for different periods [unpublished data]. Like the effects of plasma on keratinocytes, only short-term treatments with NTP showed expression of macrophage migration inhibitory factor. The integrity of healthy skin plays an important role in maintaining physiological homeostasis of the human body. Many instances are described which lead to insufficient healing necessitating further intervention. Although wound healing mechanisms and specific cell functions in wound repair have been delineated in part, many underlying pathophysiological processes are still unknown and we are only able to design new and effective wound healing therapies if we better understand this complex interplay.
The here presented new perspectives further support the enormous importance of research in this field in order to reduce the incidence of nonhealing wounds and to facilitate the healing process in general. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions.
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Forgot your password? Institutional Login Shibboleth or OpenAthens For the academic login, please select your organization on the next page. Forgot Password? Sign up for MyKarger Institutional Login. Download Fulltext PDF. Invited Review. Free Access. Related Articles for " ". Eur Surg Res ; Go to Top Abstract. FullText PDF. Abstract Background: The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body.
Microbial Symbionts Accelerate Wound Healing via the Neuropeptide Hormone Oxytocin
Karger AG, Basel Introduction Skin wound healing is a fascinating mechanism and represents an evolutionary advantage not only for mammals. From Inflammation to Proliferation One of the main reasons for skin wound healing seems to be the restoration of the barrier function in order to prevent further damage or infection. Epithelialization in Skin Wound Healing Cutaneous wounds close by epithelial resurfacing and wound contraction.
Angiogenesis in Skin Wound Healing Neovascularization represents an essential component in uncompromised wound healing due to its fundamental impact from the very beginning after skin injury until the end of the wound remodeling [ 41 , 42 ]. Cell Mol Life Sci ; First-Page Preview.
Library Recommendation. Weather permitting, some of the day will be outside amongst the herbs and flowers, in the quiet, meditation and healing part of our garden. The quieter you become the more you can hear.