Human In Vitro Skin Models for Wound Healing and Wound Healing Disorders

Botulinum toxin is a neurotoxin that has been utilized to induce chemo-denervation of muscles. Cutaneous wounds represent a special situation in which the tensile forces applied by these muscles on wound edges might have deleterious effects on the healing process. The aim of this review was to investigate such an effect and to review other mechanisms this toxin might have on the healing process. We also reviewed the role of botulinum toxin in the management of hypertrophic scars and cleft lip repair.

Angiogenesis and vasculogenesis: Inducing the growth of new blood vessels and wound healing by stimulation of bone marrow–derived progenitor cell mobilization and homing

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EFFECTS OF UNLOADING CONDITION ON WOUND HEALING PROCESS: EXPERIMENTS WITH HIRUDO MEDICINALIS

Hydrogel from Acellular Porcine Adipose Tissue Accelerates Wound Healing by Inducing Intradermal Adipocyte Regeneration

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent growth factor, which plays an important role during the process of wound healing. In clinical settings it has occasionally been employed in the treatment of cutaneous wounds of diverse etiologies. In a previous study, we have shown the positive influence of GM-CSF on full thickness excisional wounds in transgenic mice overexpressing GM-CSF in the basal layer of the epidermis. Direct GM-CSF action as well as indirect processes through the induction of secondary cytokines were proposed to contribute towards the beneficial effects. In this study, we analyzed the process of wound healing in transgenic mice overexpressing a GM-CSF antagonist in the epidermis. These mice not only exhibited a delayed scab rejection and reepithelialization but also neovascularization was reduced. The newly formed tissue was of poor quality as exhibited by the presence of extensive fibrosis. We suggest that the presence of GM-CSF in the repair process is of basic importance and its absence leads not only to delayed wound healing but it is also detrimental for the quality of the newly formed tissue.

Skin wound healing has always been a challenging subject as it involves the coordinated functioning of various cells and molecules. Any disorder in wound healing can cause healing failure and result in chronic wounds. In this study, we hypothesized that co-cultured dermal fibroblasts (DFs) and Wharton's jelly mesenchymal stem cells (WJ-MSCs) seeded on an acellular amniotic membrane scaffold could be used to promote skin regeneration in chronic ulcers. In this case series, the chronic wounds of five diabetic patients aged between 30 and 60 years were treated with co-cultured WJ-MSCs and DFs seeded on an acellular amniotic membrane. Treatment was applied and the wound healing process was evaluated every three days for nine days, with the patients being subsequently followed up for one month. The wound healing percentage, time taken for the wound to heal, and wound size were monitored. The mean wound healing rate (WHR) increased progressively in all lesions. The mean percentage of wound healing after transplantation of the biological scaffold enriched with WJ-MSCs and autologous DFs after treatment was 93.92 %, respectively. The healing percentage significantly increased after three days; significant decreases in wound size and healing time were recorded after six and nine days of treatment, respectively (P < 0.002), and Total skin regeneration and re-epithelialization were achieved by the ninth day of treatment. There were no side effects or complications. Given the current problems and complications presented by chronic wounds, Novel Clinical approaches involving cell therapy and tissue engineering can be regarded as an attractive therapeutic option for the treatment of chronic and difficult-to-heal wounds.

Growth factors and skin repair and regeneration

Radiation has many benefits and is an important treatment for cancer therapy. However, it also has unfavourable side-effects. Among these side-effects, the impairment of wound healing in the skin is a major problem in clinics. Although many attempts have been made to overcome this shortcoming, there are few effective treatments for impaired wound healing after irradiation. One reason for this is that it is hard to obtain good animal models for researching this topic. In this study, two different models were created and investigated. In one model, rectangular flaps were created on the backs of mice and irradiated while the other parts of their bodies were covered with a lead board. In another model, the lower limbs were exposed to radiation. In each model, several doses of irradiation were tested. Skin ulcers were created in the irradiated area, and the wound healing process was observed. In order to verify the usefulness of the model, adipose derived stromal cells were injected into the wound and the healing rate was calculated. In the flap model, the flaps contracted and formed linear scars. On the other hand, in the thigh model, 15 Gy irradiation resulted in slow wound healing but no strong inflammation or necrosis. The transplantation of adipose tissue derived stromal cells into the irradiated thigh wound improved the wound healing. This study suggested that irradiation of the lower limb at ∼ 15 Gy might be an appropriate model for basic research into wound healing in irradiated skin.

Interleukin 6 Indirectly Induces Keratinocyte Migration

Significance: Dermal fibroblasts are the major cell type in the skin's dermal layer. These cells originate from distinct locations of the embryo and reside in unique niches in the dermis. Different dermal fibroblasts exhibit distinct roles in skin development, homeostasis, and wound healing. Therefore, these cells are becoming attractive candidates for cell-based therapies in wound healing. Recent Advances: Human skin dermis comprises multiple fibroblast subtypes, including papillary, reticular, and hair follicle-associated fibroblasts, and myofibroblasts after wounding. Recent studies reveal that these cells play distinct roles in wound healing and contribute to diverse healing outcomes, including nonhealing chronic wound or excessive scar formation, such as hypertrophic scars (HTS) and keloids, with papillary fibroblasts having antiscarring and reticular fibroblast scar-forming properties. Critical Issues: The identities and functions of dermal fibroblast subpopulations in many respects remain unknown. In this review, we summarize the current understanding of dermal fibroblast heterogeneity, including their defined cell markers and dermal niches, dynamic changes, and contributions to skin wound healing, with the emphasis on scarless healing, healing with excessive scars (HTS and keloids), chronic wounds, and the potential application of this heterogeneity for developing cell-based therapies that allow wounds to heal faster with less scarring. Future Directions: Heterogeneous dermal fibroblast populations and their functions are poorly characterized. Refining and advancing our understanding of dermal fibroblast heterogeneity and their participation in skin homeostasis and wound healing may create potential therapeutic applications for nonhealing chronic wounds or wounds that heal with excessive scarring.

Wounds are conditions of damage and partial loss of body tissue caused by physical trauma, sharp objects, blunt objects, temperature fluctuations, chemical exposure. Wound healing is a complex interaction between cells, cytokines, mediators, and blood vessels as a natural physiological response to tissue damage. TNF-α has a crucial role in the wound healing process, facilitating body immunity, immune cell mobilization, fibroblast cell proliferation, keratinocytes, and growth factor expression. Although TNF-alpha has benefits in the early stages of wound healing, excessively high levels or a sustained inflammatory response can lead to problems, such as excessive scar tissue formation or blockages, which can impede the wound healing process. This study utilized the PRISMA-ScR (Scoping Review) protocol. A review was conducted of articles discussing the Role of TNF-Alpha in the Wound Healing Process: Molecular and Clinical Perspectives within the last 10 years. Literature search in this study using PubMed, ScienceDirect, Elsivier and Google Scolar databases Search using English, abstract and full text. After searching with the keywords: The Role of TNF-Alpha, 19,022 articles were found. The search continued using the keyword The Role of TNF-Alpha in the Wound Healing found 346 articles. The last search using the keyword The Role of TNF-Alpha in the Wound Healing: Molecular and Clinical found 26 articles. TNF-α plays an important role in the early stages of cutaneous wound healing, significantly delayed after day 3, but not by day 7. TNF-α has a crucial role in the early stages of skin wound healing, and its administration is recognized to have a positive impact on the healing response, which may pave the way for innovative strategies to address chronic skin wound healing problems.

Collecting duct epithelium and injury: Not all cells are created equal

Wound repair is a systematic biological program characterized by four overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Notwithstanding differences between species and distinct anatomical sites, the fundamental phases in the wound healing process are conserved among mammalian species. Oral wound healing is defined as an ideal wound healing model because it resolves rapidly and without scar formation. Understanding the regulation and contribution of the different molecular events that drive rapid wound healing in oral mucosa compared with those of the skin will help us define how these lesions heal more efficiently and may provide new therapeutic strategies that can be translated to the clinical settings for patients with chronic nonhealing wounds. Although all epithelial tissues have remarkable ability for tissue repair, the efficiency of such repair differs between epithelia (oral mucosa vs. cutaneous). This prompts the long-standing, fundamental biological and clinically relevant questions as to why and how does the oral mucosa achieve its enhanced wound healing capacity. In this review, we focus on (1) distinct innate wound healing capabilities of the oral mucosa, (2) lessons learned from comparative transcriptomic studies of oral mucosa versus skin, and (3) translation of findings to therapeutics for enhanced wound healing.

Skin injury is a common occurrence and mechanical forces are known to significantly impact the biological processes of skin regeneration and wound healing. Immediately following the disruption of the skin, the process of wound healing begins, bringing together numerous cell types to collaborate in several sequential phases. These cells produce a multitude of molecules and initiate multiple signaling pathways that are associated with skin disorders and abnormal wound healing, including hypertrophic scars, keloids, and chronic wounds. Studies have shown that mechanical forces can alter the microenvironment of a healing wound, causing changes in cellular function, motility, and signaling. A better understanding of the mechanobiology of cells in the skin is essential in the development of efficacious therapeutics to reduce skin disorders, normalize abnormal wound healing, and minimize scar formation.