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Special Issue "Molecular Mechanisms Related to Burns, Burn Wound Healing and Scarring"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 February 2021).

Special Issue Editors

Prof. Dr. Marc Jeschke
Website
Guest Editor
Univ Toronto, Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada
Interests: burn; trauma; stress response; inflammation; hypermetabolism, including insulin resistance; cell regeneration; gene transfer; stem cells
Prof. Dr. Lars-Peter Kamolz
Website
Guest Editor
Medizinische Universität Graz, Graz, Austria
Interests: inflammation; wound healing; fibrosis; tissue regeneration; ageing; immunity; antioxidants; obesity

Special Issue Information

Dear Colleagues,

Burn injury is a complex traumatic event with various local, regional and systemic effects. The pathophysiology of the burn patient shows the full spectrum of the complexity of inflammatory response reactions. In the acute phase, the inflammation mechanism may have negative effects because of capillary leak, the propagation of inhalation injury, and the development of multiple organ failure. Attempts to mediate these processes remain a central subject of burn care-related research. Conversely, inflammation is a necessary component in the later-stage processes of wound healing. Improvements in acute burn care have enabled patients to survive massive burns that would have once been fatal. Now, up to 70% of patients develop hypertrophic scars after burns. The functional and psychosocial sequelae remain a major rehabilitative challenge, decreasing quality of life and delaying reintegration into society. Approaches to optimizing the healing potential of burn wounds use targeted wound care and surgery to minimize the development of hypertrophic scarring. Such approaches often fail, and modulation of the established scar is continued, although the optimal indication, timing, and combination of therapies have yet to be established. The need for novel treatments is paramount, and future efforts to improve outcomes and quality of life should include optimization of wound healing to attenuate or prevent hypertrophic scarring, well-designed trials to confirm treatment efficacy, and further elucidation of molecular mechanisms to allow development of new preventive and therapeutic strategies. In this issue of the journal, we are looking for articles which deliver a profound insight into the current science of burn wound pathophysiology, burn wound healing, and scarring.

Prof. Dr. Marc Jeschke
Prof. Dr. Lars-Peter Kamolz
Guest Editors

Manuscript Submission Information

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Keywords

  • burn injury
  • wound healing
  • scarring
  • pathophysiology
  • molecular mechanism

Published Papers (7 papers)

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Research

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Open AccessArticle
Characterization of a Topically Testable Model of Burn Injury on Human Skin Explants
Int. J. Mol. Sci. 2020, 21(18), 6956; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186956 - 22 Sep 2020
Abstract
Severe burn injuries remain a major health problem due to high rates of mortality, residual morbidity, and/or aesthetic damages. To find new therapies aimed at promoting a harmonious healing of skin burns, it is important to develop models which take into account the [...] Read more.
Severe burn injuries remain a major health problem due to high rates of mortality, residual morbidity, and/or aesthetic damages. To find new therapies aimed at promoting a harmonious healing of skin burns, it is important to develop models which take into account the unique properties of the human skin. Based on previously described models of burn injury performed on human skin explants, we hypothesized that maintaining explants under constant tension forces would allow to more closely reproduce the pathophysiological processes of skin remodeling. We thus. Here, we set up and characterized an improved model of deep second-degree burn injury on ex vivo cultured human skin explants at air-liquid interface and maintained under conditions of constant tension forces. A spontaneous re-epithelialization of the lesion was observed 8 to 9 days post burn and was found to rely on the proliferation of basal keratinocytes at the wound edges. Collagen VII at the dermo-epidermal junction reformed along with the progression of re-epithelializatio and a synthesis of procollagen III was observed in the dermis at the wound site. These findings indicate that our model is suitable for the assessment of clinically-relevant therapies aimed at modulating the kinetics of re-epithelialization and/or the activation of fibroblasts following skin burn injuries. In this regard, we evaluated the use of a thermoreversible poloxamer hydrogel as a vehicle for topically-testable therapeutic molecules. Our data showed that, although useful for drug formulation, the p407/p188 poloxamer hydrogel induces a delay of skin re-epithelialization in humans skin explants submitted to experimental burn injury. Full article
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Open AccessArticle
A Comparative Study of Engineered Dermal Templates for Skin Wound Repair in a Mouse Model
Int. J. Mol. Sci. 2020, 21(12), 4508; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124508 - 25 Jun 2020
Cited by 1
Abstract
Engineered dermal templates have revolutionised the repair and reconstruction of skin defects. Their interaction with the wound microenvironment and linked molecular mediators of wound repair is still not clear. This study investigated the wound bed and acellular “off the shelf” dermal template interaction [...] Read more.
Engineered dermal templates have revolutionised the repair and reconstruction of skin defects. Their interaction with the wound microenvironment and linked molecular mediators of wound repair is still not clear. This study investigated the wound bed and acellular “off the shelf” dermal template interaction in a mouse model. Full-thickness wounds in nude mice were grafted with allogenic skin, and either collagen-based or fully synthetic dermal templates. Changes in the wound bed showed significantly higher vascularisation and fibroblast infiltration in synthetic grafts when compared to collagen-based grafts (P ≤ 0.05). Greater tissue growth was associated with higher prostaglandin-endoperoxide synthase 2 (Ptgs2) RNA and cyclooxygenase-2 (COX-2) protein levels in fully synthetic grafts. Collagen-based grafts had higher levels of collagen III and matrix metallopeptidase 2. To compare the capacity to form a double layer skin substitute, both templates were seeded with human fibroblasts and keratinocytes (so-called human skin equivalent or HSE). Mice were grafted with HSEs to test permanent wound closure with no further treatment required. We found the synthetic dermal template to have a significantly greater capacity to support human epidermal cells. In conclusion, the synthetic template showed advantages over the collagen-based template in a short-term mouse model of wound repair. Full article
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Review

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Open AccessReview
Molecular Changes Underlying Hypertrophic Scarring Following Burns Involve Specific Deregulations at All Wound Healing Stages (Inflammation, Proliferation and Maturation)
Int. J. Mol. Sci. 2021, 22(2), 897; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020897 - 18 Jan 2021
Abstract
Excessive connective tissue accumulation, a hallmark of hypertrophic scaring, results in progressive deterioration of the structure and function of organs. It can also be seen during tumor growth and other fibroproliferative disorders. These processes result from a wide spectrum of cross-talks between mesenchymal, [...] Read more.
Excessive connective tissue accumulation, a hallmark of hypertrophic scaring, results in progressive deterioration of the structure and function of organs. It can also be seen during tumor growth and other fibroproliferative disorders. These processes result from a wide spectrum of cross-talks between mesenchymal, epithelial and inflammatory/immune cells that have not yet been fully understood. In the present review, we aimed to describe the molecular features of fibroblasts and their interactions with immune and epithelial cells and extracellular matrix. We also compared different types of fibroblasts and their roles in skin repair and regeneration following burn injury. In summary, here we briefly review molecular changes underlying hypertrophic scarring following burns throughout all basic wound healing stages, i.e. during inflammation, proliferation and maturation. Full article
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Open AccessReview
Burns in the Elderly: Potential Role of Stem Cells
Int. J. Mol. Sci. 2020, 21(13), 4604; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134604 - 29 Jun 2020
Abstract
Burns in the elderly continue to be a challenge despite advances in burn wound care management. Elderly burn patients continue to have poor outcomes compared to the younger population. This is secondary to changes in the quality of the aged skin, leading to [...] Read more.
Burns in the elderly continue to be a challenge despite advances in burn wound care management. Elderly burn patients continue to have poor outcomes compared to the younger population. This is secondary to changes in the quality of the aged skin, leading to impaired wound healing, aggravated immunologic and inflammatory responses, and age-related comorbidities. Considering the fast-growing elderly population, it is imperative to understand the anatomic, physiologic, and molecular changes of the aging skin and the mechanisms involved in their wound healing process to prevent complications associated with burn wounds. Various studies have shown that stem cell-based therapies improve the rate and quality of wound healing and skin regeneration; however, the focus is on the younger population. In this paper, we start with an anatomical, physiological and molecular dissection of the elderly skin to understand why wound healing is delayed. We then review the potential use of stem cells in elderly burn wounds, as well as the mechanisms by which mesenchymal stem cell (MSCs)-based therapies may impact burn wound healing in the elderly. MSCs improve burn wound healing by stimulating and augmenting growth factor secretion and cell proliferation, and by modulating the impaired elderly immune response. MSCs can be used to expedite healing in superficial partial thickness burns and donor site wounds, improve graft take and prevent graft breakdown. Full article
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Open AccessReview
Post-Burn Pruritus
Int. J. Mol. Sci. 2020, 21(11), 3880; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21113880 - 29 May 2020
Cited by 3
Abstract
Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious complication of burn injury, which severely lowers the quality of life of the patient. Many potential treatments [...] Read more.
Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious complication of burn injury, which severely lowers the quality of life of the patient. Many potential treatments are available for pruritus but there is no consensus of the best single treatment yet. The precise mechanism of post-burn pruritus has not been elucidated, but it appears to have pruritogenic and neuropathic aspects. Clinically, post-burn pruritus tends to be intractable to conventional treatment but rather responds to neuroleptic agents, such as gabapentin and pregabalin. During wound healing, various neuropeptides secreted from the nerves of the skin control epidermal and vascular proliferation and connective tissue cells. When keratinocytes are activated by an itch-inducing substance, they secrete a variety of inflammatory substances that increase the susceptibility of the itch receptor. There are two mechanisms underlying post-burn neuropathic pruritus. The first one is peripheral sensitization. The second one is the intact nociceptor hypothesis. An effective treatment for post-burn pruritus will also be effective in other neuropathic and intractable itching. In this review, we summarized the interaction and mechanism of keratinocytes, immune cells, and nerve fibers related to post-burn pruritus. Full article
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Open AccessReview
Mechanosensitive Aspects of Cell Biology in Manual Scar Therapy for Deep Dermal Defects
Int. J. Mol. Sci. 2020, 21(6), 2055; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062055 - 17 Mar 2020
Abstract
Deep dermal defects can result from burns, necrotizing fasciitis and severe soft tissue trauma. Physiological scar restriction during wound healing becomes increasingly relevant in proportion to the affected area. This massively restricts the general mobility of patients. External mechanical influences (activity or immobilization [...] Read more.
Deep dermal defects can result from burns, necrotizing fasciitis and severe soft tissue trauma. Physiological scar restriction during wound healing becomes increasingly relevant in proportion to the affected area. This massively restricts the general mobility of patients. External mechanical influences (activity or immobilization in everyday life) can lead to the formation of marked scar strands and adhesions. Overloading results in a renewed inflammatory reaction and thus in further restriction. Appropriate mechanical stimuli can have a positive influence on the scar tissue. “Use determines function,” and even minimal external forces are sufficient to cause functional alignment (mechanotransduction). The first and second remarkable increases in connective tissue resistance (R1 and R2) seem to be relevant clinical indications of adequate dosage in the proliferation and remodulation phase, making it possible to counteract potential overdosage in deep dermal defects. The current state of research does not allow a direct transfer to the clinical treatment of large scars. However, the continuous clinical implementation of study results with regard to the mechanosensitivity of isolated fibroblasts, and the constant adaptation of manual techniques, has nevertheless created an evidence-base for manual scar therapy. The manual dosages are adapted to tissue physiology and to respective wound healing phases. Clinical observations show improved mobility of the affected regions and fewer relapses into the inflammatory phase due to mechanical overload. Full article
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Open AccessReview
New Nanotechnologies for the Treatment and Repair of Skin Burns Infections
Int. J. Mol. Sci. 2020, 21(2), 393; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020393 - 08 Jan 2020
Cited by 14
Abstract
Burn wounds are highly debilitating injuries, with significant morbidity and mortality rates worldwide. In association with the damage of the skin integrity, the risk of infection is increased, posing an obstacle to healing and potentially leading to sepsis. Another limitation against healing is [...] Read more.
Burn wounds are highly debilitating injuries, with significant morbidity and mortality rates worldwide. In association with the damage of the skin integrity, the risk of infection is increased, posing an obstacle to healing and potentially leading to sepsis. Another limitation against healing is associated with antibiotic resistance mainly due to the use of systemic antibiotics for the treatment of localized infections. Nanotechnology has been successful in finding strategies to incorporate antibiotics in nanoparticles for the treatment of local wounds, thereby avoiding the systemic exposure to the drug. This review focuses on the most recent advances on the use of nanoparticles in wound dressing formulations and in tissue engineering for the treatment of burn wound infections. Full article
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