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Developing extracellular matrix-derived hydrogel with a fast self-healing capacity to provide a sustainable moist environment able to accelerate wound healing is highly desired for full-thickness skin wound repair. In this study, a fast self-healing hyaluronic acid hydrogel with a dual dynamic network was constructed through a primary reversible acylhydrazone bond formed between aldehyde-modified hyaluronic acid, 3,3'-dithiobis (propionyl hydrazide) (DTP), and secondary dynamic ionic interactions between κ-carrageenan (KC) and K + . Because of the presence of various dynamic covalent bonds such as the acylhydrazone bond, disulfide bond, and noncovalent bonds including hydrogen bonding and ionic interactions, as well as the notable thermoreversible nature of KC, the resultant hydrogel could be self-healed rapidly within 30 min under physiological temperature with a self-healing efficiency of 100%, which was significantly better than other hyaluronic acid hydrogels, as reported previously. Besides, the hydrogel displayed excellent cytocompatibility. According to this study, the hydrogel was administered into the wounds and achieved a superior performance of promoting full-thickness skin wound healing by increasing granulation tissue formation, deposition of collagen as well as the acceleration of re-epithelialization and neovascularization, compared to commercial products, e.g., gauze and 3 M hydrocolloid. We also anticipate that this strategy of double-dynamic network cross-linking can be adopted to fabricate self-healing materials for multiple applications.

Background: Wound healing is a multistep process involving coordinated responses of a variety of cell types, cytokines, growth factors, and extracellular matrix (ECM) components leading to the physiological restoration of tissue integrity. Photobiomodulation therapy (PBMT) has been highlighted as an approach to improve the healing process, nonetheless at the molecular level, the effects of PBMT are not entirely understood., Aim: To systematically review publications that investigated gene expression after PBMT during in vivo skin repair., Methods: An electronic search was undertaken in Medline Ovid (Wolters Kluwer), PubMed (National Library of Medicine), Web of Science (Thomson Reuters), Scopus (Elsevier), Embase, and LILACS databases. The search strategy was conducted from the terms: low-level light therapy, gene expression, and wound healing and their synonyms. The databases were consulted in December 2023 and no publication year limit was used., Results: Eleven studies were included in this review and the expression of 186 genes was evaluated. PBMT modified the expression of several targets genes studied, such as down-regulation of genes related to extracellular matrix proteases (MMP2 and MMP9) and pro-inflammatory cytokines (IL10 and IL6) and up-regulation of DNMT3A and BFGF., Conclusion: This review demonstrates that PBMT is capable of regulating gene expression during wound healing. Most evidence showed a positive impact of PBMT in regulating genes linked to inflammatory cytokines improving skin wound healing. Yet, the effects of PBMT in genes involved in other mechanisms still need to be better understood., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si 4+ ) and calcium ions (Ca 2+ ), have been shown to assist in wound repair. The Si 4+ released from silica (SiO 2 ) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca 2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO 2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO 2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCP x @SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCP x @SSF aerogels may be valuable for wound healing.

Oxygen is a critical factor that can regulate the wound healing processes such as skin cell proliferation, granulation, re-epithelialization, angiogenesis, and tissue regeneration. However, hypoxia, a common occurrence in the wound bed, can impede normal healing processes. To enhance wound healing, oxygenation strategies that could effectively increase wound oxygen levels are effective. The present review summarizes wound healing stages and the role of hypoxia in wound healing and overviews current strategies to incorporate various oxygen delivery or generating materials for wound dressing, including catalase, nanoenzyme, hemoglobin, calcium peroxide, or perfluorocarbon-based materials, in addition to photosynthetic bacteria and hyperbaric oxygen therapy. Mechanism of action, oxygenation efficacy, and potential benefits and drawbacks of these dressings are also discussed. We conclude by highlighting the importance of design optimization in wound dressings to address the clinical needs to improve clinical outcomes.

The limited ability of mammals to regenerate has garnered significant attention, particularly in regard to skin wound healing (WH), which is a critical step for regeneration. In human adults, skin WH results in the formation of scars following injury or trauma, regardless of severity. This differs significantly from the scarless WH observed in the fetal skin of mammals or anamniotes. This review investigates the role of molecular players involved in scarless WH, which are lost or repressed in adult mammalian WH systems. Specifically, we analyze the physiological role of Anterior Gradient (AGR) family proteins at different stages of the WH regulatory network. AGR is activated in the regeneration of lower vertebrates at the stage of wound closure and, accordingly, is important for WH. Mammalian AGR2 is expressed during scarless WH in embryonic skin, while in adults, the activity of this gene is normally inhibited and is observed only in the mucous epithelium of the digestive tract, which is capable of full regeneration. The combination of AGR2 unique potencies in postnatal mammals makes it possible to consider it as a promising candidate for enhancing WH processes.

Severe traumatic wounds and burns have a high chance of mortality and can leave survivors with many functional disabilities and cosmetic problems, including scars. The healing process requires a harmonious interplay of various cells and growth factors. Different structures of the skin house numerous cells, matrix components and growth factors. Any disturbance in the balance between these components can impair the healing process. The function of cells and growth factors can be manipulated and facilitated to aid tissue repair. In the current review, the authors focus on the importance of the skin microenvironment, the pathophysiology of various types of burns, mechanisms and factors involved in skin repair and wound healing and regeneration of the skin using tissue engineering approaches.

Wound healing is a complex process based on the coordinated signaling molecules and dynamic interactions between the engineered scaffold and newly formed tissue. So far, most of the engineered scaffolds used for the healing of full-thickness skin wounds do not mimic the natural extracellular matrix (ECM) complexity and therefore are not able to provide an appropriate niche for endogenous tissue regeneration [1]. To address this gap and to accelerate the wound healing process, we present biomimetic bilayer scaffolds compositing of gelatin nanofibers (GFS) and photocrosslinkable composite hydrogels loaded with epidermal growth factors (EGF). The nanofibers operate as the dermis layer, and EGF-loaded composite hydrogels acted as the epidermis matrix for the full-thickness wound healing application. The hydrogels are composed of gelatin metacryloyl (GelMA) modified with silicate nanoplatelets (Laponite). To overcome the challenges of transdermal delivery of EGF, including short half-life and lack of efficient formulation precise, controlled delivery was attained by immobilization of EGF on Laponite. It is shown that the addition of 1wt% silicate nanoplatelet increases the compressive modulus of the hydrogels by 170%. In vitro wound closure analysis also demonstrated improved adhesion of the scaffolds to the native tissue by 3.5 folds. Moreover, the tunable hemostatic ability of the scaffolds due to the negatively charged nanoplatelets is shown. In an established excisional full-thickness wound model, an enhanced wound closure (up to 93.1 ± 1.5%) after 14 days relative to controls (GFS and saline-treated groups) is demonstrated. The engineered adhesive and hemostatic scaffolds with sustained release of the growth factors have the potential to stimulate complete skin regeneration for full-thickness wound healing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Cutaneous lesions lead to complications in patients, since they may be recurrent and also represent risk of progression to infection and/or amputation. Therefore, effective, protective, and topical treatments of easy application and removal need to be developed to provide effective alternatives to patients. The Caryocar brasiliense Cambess (CBC) presents important pharmacological activities and proved in the healing process. This paper reports the improvement of the CBC nanostructured (LNC CBC and LNC CBC+ ) activity in dermal wounds in vivo. The oil was physico-chemically characterized and used in the development of lipid-core nanocapsules (LNCs), coated (LNC CBC+ ) or without chitosan (LNC CBC ), in concentration of 1.0 mg mL -1 . Hydrogel (HG) was tested in vivo on lesions in the back of male Wistar rats for 14 days. The oil presented appropriate physico-chemical characteristics for its use, such as moisture 0.76 %, acidity 0.85 % and oleic acid 25.90 %. The LNCs showed nanometric size (around 200 nm), monomodal distribution, slight acid pH and zeta potential of + 22.1 mV in accordance with the composition. The nanostructured oil induced dermal healing in vivo showing significantly better improvement than free oil. LNC CBC+ showed best results showing the higher increase of the production of type 1 collagen, an important protein to the healing repair. These results suggest that development of formulations LNC CBC and LNC CBC+ are promising and important alternative for the treatment of dermal wounds, avoiding complications related to cutaneous lesions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The basic fibroblast growth factor (bFGF) plays an important role in the wound repair process. However, lacking of better biomaterials to carry bFGF still is a challenge in skin repair and regeneration. In this study, the human-like collagen (HLC) cross-linked with transglutaminase (TG) to fabricate a HLC/TG hydrogel to load bFGF. The physical properties of hydrogel, such as interior structure, mechanical property, were characterized in vitro using scanning electron microscopy (SEM), rheometer. Then, the effects of the HLC/TG hydrogel on the bFGF and cell attachmentwere evaluated, and the results showed that the HLC/TG hydrogel has good biocompatibility towards bFGF and cells. Finally, skin wound healing test was performed for the evaluation of HLC/TG hydrogels with bFGF in a mouse model. All results of macroscopic and microscopic analysis indicated that not only our HLC/TG hydrogel provide a delivery of growth factors, but also the HLC/TG hydrogel with bFGF achieving better skin regeneration in the structure and function.

Topographical cues at nanoscale are important to sustain an environment capable of controlling cell behavior. This work presents a novel approach for the fabrication of nanotopographical patterned polymeric nanofibers. Also, the influence of nanofibrous patterns on accelerated directional migration and proliferation of cells was investigated on this work. For the fabrication of scab-inspired nanofibrous membrane, a polycaprolactone (PCL) containing with collagen nanofibrous mats with various nanotopographical patterns were fabricated. Nanotopographical pattern provides hierarchical cellular control by directing morphology of cells and influencing formation of integrin on the nanoscale. Moreover, the cellular infiltration of membrane was tested to evaluate wound healing progression using a function of confocal Z-depth. As a result, various factors such as the fibers orientation of the scaffold and the depth of cell penetration have been shown to affect wound healing. Fibroblasts were ordered and polarized with the aligned nanofibers, showing aligned cytoskeleton stress and robust focal adhesions at the cells' leading edge. This nanofabrication approach has potential applications as multifunctional biomaterials for rapid wound healing, scaffold-based cellular control, and biomedical technology., (Copyright © 2018. Published by Elsevier B.V.)

During the resolution phase of normal skin wound healing, there is a considerable loss of various cell types, including myofibroblasts by apoptosis. Inappropriate delay of apoptosis, and thus increased survival of myofibroblasts, may be a factor leading to pathologies and excessive scarring. Considerable data now clearly suggest that innervation plays a major role in wound healing, including the modulation of fibroblast cellular activity. An abnormal level of neuromediators is implicated not only in the development of chronic wounds but also in excessive scar formation. Understanding interactions between neuromediators and myofibroblasts, allowing normal reinnervation and having adequate levels of neuromediators during the healing process are clearly important to avoid the appearance of pathological healing or fibrosis/scarring. The aim of this review was first to discuss the mechanisms leading to normal or excessive scarring and then to present the roles of innervation during wound healing. Finally, the latest therapeutic strategies to help wound repair and reinnervation after skin damage will be introduced. Advantages and limitations in the use of neuropeptides, growth factors and biomaterials will be discussed as well as the most recent studies on electrostimulation and the potential of targeting resident skin mesenchymal stem cells., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Porous bioscaffolds are applied to facilitate skin repair since the early 1990s, but a perfect regeneration outcome has yet to be achieved. Until now, most efforts have focused on modulating the chemical properties of bioscaffolds, while physical properties are traditionally overlooked. Recent advances in mechanobiology and mechanotherapy have highlighted the importance of biomaterials' physical properties in the regulation of cellular behaviors and regenerative processes. In skin repair, the mechanical and structural features of porous bioscaffolds are two major physical properties that determine therapeutic efficacy. Here, first an overview of natural skin repair with an emphasis on the major biophysically sensitive cell types involved in this multistage process is provided, followed by an introduction of the four roles of bioscaffolds as skin implants. Then, how the mechanical and structural features of bioscaffolds influence these four roles is discussed. The mechanical and structural features of porous bioscaffolds should be tailored to balance the acceleration of wound closure and functional improvements of the repaired skin. This study emphasizes that decoupling and precise control of the mechanical and structural features of bioscaffolds are significant aspects that should be considered in future biomaterial optimization, which can build a foundation to ultimately achieve perfect skin regeneration outcomes., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The importance of skin to survival, and the devastating physical and psychological consequences of scarring following reparative healing of extensive or difficult to heal human wounds, cannot be disputed. We discuss the significant challenges faced by patients and healthcare providers alike in treating these wounds. New state of the art technologies have provided remarkable insights into the role of skin stem and progenitor cells and their niches in maintaining skin homeostasis and in reparative wound healing. Based on this knowledge, we examine different approaches to repair extensive burn injury and chronic wounds, including full and split thickness skin grafts, temporising matrices and scaffolds, and composite cultured skin products. Notable developments include next generation skin substitutes to replace split thickness skin autografts and next generation gene editing coupled with cell therapies to treat genodermatoses. Further refinements are predicted with the advent of bioprinting technologies, and newly defined biomaterials and autologous cell sources that can be engineered to more accurately replicate human skin architecture, function and cosmesis. These advances will undoubtedly improve quality of life for patients with extensive burns and difficult to heal wounds., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The treatment of full thickness skin loss, which can be extensive in the case of large burns, continues to represent a challenging clinical entity. This is due to an on-going inability to produce a suitable tissue engineered substrate that can satisfactorily replicate the epidermal and dermal in vivo niches to fulfil both aesthetic and functional demands. The current gold standard treatment of autologous skin grafting is inadequate because of poor textural durability, scarring and associated contracture, and because of a paucity of donor sites in larger burns. Tissue engineering has seen exponential growth in recent years with a number of 'off-the-shelf' dermal and epidermal substitutes now available. Each has its own limitations. In this review, we examine normal wound repair in relation to stem/progenitor cells that are intimately involved in this process within the dermal niche. Endothelial precursors, in particular, are examined closely and their phenotype, morphology and enrichment from multiple sources are described in an attempt to provide some clarity regarding the controversy surrounding their classification and role in vasculogenesis. We also review the role of the next generation of cellularized scaffolds and smart biomaterials that attempt to improve the revascularisation of artificial grafts, the rate of wound healing and the final cosmetic and functional outcome., (Copyright © 2013 John Wiley & Sons, Ltd.)

Current therapy for skin wound healing still relies on skin transplantation. Many studies were done to try to find out ways to replace skin transplantation, but there is still no effective alternative therapy. In this study, decellularized scaffolds were prepared from pig peritoneum by a series of physical and chemical treatments, and scaffolds loaded with hyaluronic acid (HA) and epidermal growth factor (EGF) were tested for their effect on wound healing. MTT assay showed that EGF increased NIH3T3 cell viability and confirmed that EGF used in this study was biologically active in vitro. Scanning electron microscope (SEM) showed that HA stably attached to scaffolds even after soaking in PBS for 48 h. ELISA assay showed that HA increased the adsorption of EGF to scaffolds and sustained the release of EGF from scaffolds. Animal study showed that the wounds covered with scaffolds containing HA and EGF recovered best among all 4 groups and had wound healing rates of 49.86%, 70.94% and 87.41% respectively for days 10, 15 and 20 post-surgery compared to scaffolds alone with wound healing rates of 29.26%, 42.80% and 70.14%. In addition, the wounds covered with scaffolds containing EGF alone were smaller than no EGF scaffolds on days 10, 15 and 20 post-surgery. Hematoxylin-Eosin (HE) staining confirmed these results by showing that on days 10, 15 and 20 post-surgery, the thicker epidermis and dermis layers were observed in the wounds covered with scaffolds containing HA and EGF than scaffolds alone. In addition, the thicker epidermis and dermis layers were also observed in the wounds covered with scaffolds containing EGF than scaffolds alone. Skin appendages were observed on day 20 only in the wound covered with scaffolds containing HA and EGF. These results demonstrate that the scaffolds containing HA and EGF can enhance wound healing., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This study investigates the influence of gallium-arsenide (GaAs) laser photobiostimulation applied with different energy densities on skin wound healing by secondary intention in rats. Three circular wounds, 10 mm in diameter, were made on the dorsolateral region of 21 Wistar rats weighting 282.12 ± 36.08 g. The animals were equally randomized into three groups: Group SAL, saline solution 0.9%; Group L3, laser GaAs 3 J/cm(2); Group L30, laser GaAs 30 J/cm(2). Analyses of cells, blood vessels, collagen and elastic fibres, glycosaminoglycans and wound contraction were performed on the scar tissue from different wounds every 7 days for 21 days. On day 7, 14 and 21, L3 and L30 showed higher collagen and glycosaminoglycan levels compared to SAL (P < 0.05). At day 21, elastic fibres were predominant in L3 and L30 compared to SAL (P < 0.05). Type-III collagen fibres were predominant at day 7 in both groups. There was gradual reduction in these fibres and accumulation of type-I collagen over time, especially in L3 and L30 compared with SAL. Elevated density of blood vessels was seen in L30 on days 7 and 14 compared to the other groups (P < 0.05). On these same days, there was higher tissue cellularity in L3 compared with SAL (P < 0.05). The progression of wound closure during all time points investigated was higher in the L30 group (P < 0.05). Both energy densities investigated increased the tissue cellularity, vascular density, collagen and elastic fibres, and glycosaminoglycan synthesis, with the greater benefits for wound closure being found at the density of 30 J/cm(2)., (© 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.)

Background: The COVID‐19 pandemic brought about a new normal, necessitating the use of personal protective equipment (PPE) like face shields, surgical masks, gloves, and goggles. However, prolonged mask‐wearing introduced skin‐related issues due to changes in the skin's microenvironment, including increased humidity and temperature, as well as pressure on the skin. These factors led to skin deformation, vascular issues, edema, and inflammation, resulting in discomfort and cosmetic concerns. Clinical reports quickly highlighted the consequences of long‐term mask use, including increased cases of "maskne" (mask‐related acne) or mask‐wearing related disorders such as rosacea flare‐ups, skin‐barrier defects, itching, erythema, redness, hyperpigmentation, and lichenification. Some of these issues, like inflammation, oxidative stress, and poor wound healing, could be directly linked to acne‐related disorders or skin hypoxia. Aim: To address these problems, researchers turned to rutin, a well‐known flavonoid with antioxidant, vasoactive, and anti‐inflammatory properties. However, rutin's poor water solubility presented a challenge for cosmetic formulations. To overcome this limitation, a highly water‐soluble form of rutin was developed, making it suitable for use at higher concentrations. Methods: In vitro and ex vivo tests were conducted, as well as an innovative clinical trial including volunteers wearing surgical masks for at least 2 h, to evaluate the biological activity of this soluble rutin on the main skin concerns associated with mask‐wearing (inflammation, oxidative stress, skin repair, hyperpigmentation, and skin redness). Results: The in vitro results showed that the active ingredient significantly reduced oxidative stress, improved wound healing, and reduced inflammation. In dark skin explants, the active ingredient significantly reduced melanin content, indicating its lightening activity. This effect was confirmed in the clinical study, where brown spots decreased significantly after 4 days of application. Moreover, measurements on volunteers demonstrated a decrease in skin redness and vascularization after the active ingredient application, indicating inflammation and erythema reduction. Volunteers reported improved skin comfort. Conclusion: In summary, the COVID‐19 pandemic led to various skin issues associated with mask‐wearing. A highly soluble form of rutin was developed, which effectively addressed these concerns by reducing inflammation, oxidative stress, and hyperpigmentation while promoting wound healing. This soluble rutin offers a promising solution for the rapid treatment of maskne‐related disorders and other skin problems caused by prolonged mask use. [ABSTRACT FROM AUTHOR]

Background. Burn wound healing is recognized as a complex process involving synergetic interactions between different cells, cytokines and growth factors. The adverse interactions can underlie chronicization of the process. Accordingly, the paper presents a relevant study into mechanisms of natural wound dressings, capable of influencing the processes of inflammation, angiogenesis, and skin resurfacing.Objective. To carry out a comparative evaluation of efficiency of burn wound healing with derma-based hydrogel according to the dynamics of proand anti-inflammatory factors.Methods. Development of a hydrogel material involved dermis samples of Landrace breed of pig, subjected to partial alkaline hydrolysis. In order to carry out a comparative evaluation of burn wound healing efficiency, the authors simulated direct thermal injury in three groups of sphinx (hairless) rats: group 1 (control group) — rats without treatment (n = 20), group 2 (comparison group) — rats treated with Levomekol ointment (n = 20), and group 3 (experimental group) — rats treated with hydrogel material (n = 20). Before and after injuring on days 1, 3, 7, 14, the content of cytokines interleukin-1β, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α by enzyme immunoassay. The wound samples were explanted for histological examination on days 3, 7 and 14 after the beginning of the experiment. Statistical processing of the obtained results on DNA content in hydrogel, cytokine content in serum and morphometric data was performed using GraphPadPrism 6.04, Microsoft Excel 2016 (Microsoft, USA).Results. When determining the content dynamics of nonspecific markers of inflammation, an increase in the concentrations of interleukin-1β and tumor necrosis factor-α on day 1 after the hydrogel application was recorded, as well as an increase in interleukin-6 on days 3 and 7, while the concentrations of interleukin-8 did not change significantly throughout the experiment. Thus, dermal components are indicated to participate in the inhibition of acute-phase immune reactions. With regard to anti-inflammatory factors, the study revealed a decrease in the concentration of interleukin-10 on days 1 and 7, an increase in interleukin-4 on day 3 as compared to the control group, thereby indicating a pronounced anti-inflammatory effect and prolonged action of the hydrogel.Conclusion. Comparative analysis of the pro-inflammatory cytokines levels (interleukin-1β, interleukin-8) showed pronounced anti-inflammatory effects of the derma-based hydrogel material. Introduction of exogenous biological components of the extracellular matrix (collagen and its hydrolysates) had a significant influence on the regulation of anti-inflammatory cytokines synthesis, presumably contributing to faster successful epithelization and wound healing.

Objectives: Skin barrier properties are critical for maintaining epidermal water content, protecting from environmental factors and providing the first line of defense against pathogens. In this study, we investigated the non‐proteinogenic amino acid L‐4‐Thiazolylalanine (L4) as a potential active ingredient in skin protection and barrier strength. Methods: L4 on wound healing, anti‐inflammatory and anti‐oxidant properties were evaluated using monolayers and 3D skin equivalents. The transepithelial electrical resistance (TEER) value was used in vitro as a strong indicator of barrier strength and integrity. Clinical L4 efficacy was assessed for the evaluation of the skin barrier integrity and soothing benefits. Results: In vitro treatments of L4 show beneficial effects in wound closure mechanism, and we demonstrate that L4 anti‐oxidant benefits with markedly increased HSP70 and decreased reactive oxygen species production induced by UVs exposure. Barrier strength and integrity were significantly improved by L4, confirmed clinically by an increase in 12R‐lipoxygenase enzymatic activity in the stratum corneum. In addition, soothing benefits of L4 have been shown clinically with the decrease in redness after methyl nicotinate application on the inner arm and the significant reduction of the erythema and the skin desquamation on the scalp. Conclusion: L4 delivered multiple skin benefits by strengthening the skin barrier, accelerating the skin repair process as well as soothing the skin and the scalp with anti‐inflammaging effects. The observed efficacy validates L4 as a desirable skincare ingredient for topical treatment. [ABSTRACT FROM AUTHOR]

Wound healing is the body's process of injury recovery. Skin healing is divided into four distinct overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Cell-to-cell interactions mediated by both cytokines and chemokines are imperative for the transition between these phases. Patients can face difficulties in the healing process due to the wound being too large, decreased vascularization, infection, or additional burdens of a systemic illness. The field of tissue engineering has been investigating biomaterials as an alternative for skin regeneration. Biomaterials used for wound healing may be natural, synthetic, or a combination of both. Once a specific biomaterial is selected, it acts as a scaffold for skin regeneration. When the scaffold is applied to a wound, it allows for the upregulation of distinct molecular signaling pathways important for skin repair. Although tissue engineering has made great progress, more research is needed in order to support the use of biomaterials for wound healing for clinical translation. [ABSTRACT FROM AUTHOR]

Skin repair encompasses epidermal barrier repair and wound healing which involves multiple cellular and molecular stages. Therefore, many skin repair strategies have been proposed. In order to characterize the usage frequency of skin repair ingredients in cosmetics, medicines, and medical devices, commercialized in Portuguese pharmacies and parapharmacies, a comprehensive analysis of the products' composition was performed. A total of 120 cosmetic products, collected from national pharmacies online platforms, 21 topical medicines, and 46 medical devices, collected from INFARMED database, were included in the study, revealing the top 10 most used skin repair ingredients in these categories. A critical review regarding the effectiveness of the top ingredients was performed and an in-depth analysis focused on the top three skin repair ingredients pursued. Results demonstrated that top three most used cosmetic ingredients were metal salts and oxides (78.3%), vitamin E and its derivatives (54.2%), and Centella asiatica (L.) Urb. extract and actives (35.8%). Regarding medicines, metal salts and oxides were also the most used (47.4%) followed by vitamin B5 and derivatives (23.8%), and vitamin A and derivatives (26.3%). Silicones and derivatives were the most common skin repair ingredients in medical devices (33%), followed by petrolatum and derivatives (22%) and alginate (15%). This work provides an overview of the most used skin repair ingredients, highlighting their different mechanisms of action, aiming to provide an up-to-date tool to support health professionals' decisions. [ABSTRACT FROM AUTHOR]

The repair of skin injury has always been a concern in the medical field. As a kind of biopolymer material with a special network structure and function, collagen-based hydrogel has been widely used in the field of skin injury repair. In this paper, the current research and application status of primal hydrogels in the field of skin repair in recent years are comprehensively reviewed. Starting from the structure and properties of collagen, the preparation, structural properties, and application of collagen-based hydrogels in skin injury repair are emphatically described. Meanwhile, the influences of collagen types, preparation methods, and crosslinking methods on the structural properties of hydrogels are emphatically discussed. The future and development of collagen-based hydrogels are prospected, which is expected to provide reference for the research and application of collagen-based hydrogels for skin repair in the future. [ABSTRACT FROM AUTHOR]

The repair process for oral and maxillofacial injuries involves hemostasis, inflammation, proliferation, and remodeling. Injury repair involves a variety of cells, including platelets, immune cells, fibroblasts, and various cytokines. Rapid and adequate healing of oral and maxillofacial trauma is a major concern to patients. Functional drug-delivery hydrogels play an active role in promoting wound healing and have shown unique advantages in wound dressings. Functional hydrogels promote wound healing through their adhesive, anti-inflammatory, antioxidant, antibacterial, hemostatic, angiogenic, and re-epithelialization-promoting properties, effectively sealing wounds and reducing inflammation. In addition, functional hydrogels can respond to changes in temperature, light, magnetic fields, pH, and reactive oxygen species to release drugs, enabling precise treatment. Furthermore, hydrogels can deliver various cargos that promote healing, including nucleic acids, cytokines, small-molecule drugs, stem cells, exosomes, and nanomaterials. Therefore, functional drug-delivery hydrogels have a positive impact on the healing of oral and maxillofacial injuries. This review describes the oral mucosal structure and healing process and summarizes the currently available responsive hydrogels used to promote wound healing.

Hydrogels can imitate the extracellular matrix, therefore facilitating the creation of an ideal healing environment for wounds. Consequently, they are popular as a material choice for wound dressings. Polysaccharides have been widely used in wound dressings due to their good biocompatibility and degradability. In this study, we first discuss skin and wound physiology before summarizing the methods for producing hydrogels from polysaccharides and their derivatized. These include not just normal polysaccharides like chitosan, cellulose, and alginate, but also Chinese medicinal polysaccharides with therapeutic properties. Then, strategies for causing hydrogel production from polysaccharides or their derivatives are briefly explained. Finally, the functions of hydrogel dressings are reviewed, including antibacterial, antioxidant, and adhesive properties, as well as the methods for achieving these properties. Furthermore, current issues and concerns are discussed, with the goal of providing fresh paths for the development of future wound dressings. [Display omitted] [ABSTRACT FROM AUTHOR]

Wound healing is the body’s process of injury recovery. Skin healing is divided into four distinct overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Cell-to-cell interactions mediated by both cytokines and chemokines are imperative for the transition between these phases. Patients can face difficulties in the healing process due to the wound being too large, decreased vascularization, infection, or additional burdens of a systemic illness. The field of tissue engineering has been investigating biomaterials as an alternative for skin regeneration. Biomaterials used for wound healing may be natural, synthetic, or a combination of both. Once a specific biomaterial is selected, it acts as a scaffold for skin regeneration. When the scaffold is applied to a wound, it allows for the upregulation of distinct molecular signaling pathways important for skin repair. Although tissue engineering has made great progress, more research is needed in order to support the use of biomaterials for wound healing for clinical translation.

Skin acts as an essential barrier, protecting organisms from their environment. For skin trauma caused by accidental injuries, rapid healing, personalization, and functionality are vital requirements in clinical, which are the bottlenecks hindering the translation of skin repair from benchside to bedside. Herein, we described a novel design and a proof‐of‐concept demonstration of an adaptive bioprinting robot to proceed rapid in situ bioprinting on a full‐thickness excisional wound in mice. The three‐dimensional (3D) scanning and closed‐loop visual system integrated in the robot and the multi‐degree‐of‐freedom mechanism provide immediate, precise, and complete wound coverage through stereotactic bioprinting, which hits the key requirements of rapid‐healing and personalization in skin repair. Combined with the robot, epidermal stem cells and skin‐derived precursors isolated from neonatal mice mixed with Matrigel were directly printed into the injured area to replicate the skin structure. Excisional wounds after bioprinting showed complete wound healing and functional skin tissue regeneration that closely resembling native skin, including epidermis, dermis, blood vessels, hair follicles and sebaceous glands etc. This study provides an effective strategy for skin repair through the combination of the novel robot and a bioactive bioink, and has a promising clinical translational potential for further applications. [ABSTRACT FROM AUTHOR]

The limited ability of mammals to regenerate has garnered significant attention, particularly in regard to skin wound healing (WH), which is a critical step for regeneration. In human adults, skin WH results in the formation of scars following injury or trauma, regardless of severity. This differs significantly from the scarless WH observed in the fetal skin of mammals or anamniotes. This review investigates the role of molecular players involved in scarless WH, which are lost or repressed in adult mammalian WH systems. Specifically, we analyze the physiological role of Anterior Gradient (AGR) family proteins at different stages of the WH regulatory network. AGR is activated in the regeneration of lower vertebrates at the stage of wound closure and, accordingly, is important for WH. Mammalian AGR2 is expressed during scarless WH in embryonic skin, while in adults, the activity of this gene is normally inhibited and is observed only in the mucous epithelium of the digestive tract, which is capable of full regeneration. The combination of AGR2 unique potencies in postnatal mammals makes it possible to consider it as a promising candidate for enhancing WH processes.

Skin repair encompasses epidermal barrier repair and wound healing which involves multiple cellular and molecular stages. Therefore, many skin repair strategies have been proposed. In order to characterize the usage frequency of skin repair ingredients in cosmetics, medicines, and medical devices, commercialized in Portuguese pharmacies and parapharmacies, a comprehensive analysis of the products’ composition was performed. A total of 120 cosmetic products, collected from national pharmacies online platforms, 21 topical medicines, and 46 medical devices, collected from INFARMED database, were included in the study, revealing the top 10 most used skin repair ingredients in these categories. A critical review regarding the effectiveness of the top ingredients was performed and an in-depth analysis focused on the top three skin repair ingredients pursued. Results demonstrated that top three most used cosmetic ingredients were metal salts and oxides (78.3%), vitamin E and its derivatives (54.2%), and Centella asiatica (L.) Urb. extract and actives (35.8%). Regarding medicines, metal salts and oxides were also the most used (47.4%) followed by vitamin B5 and derivatives (23.8%), and vitamin A and derivatives (26.3%). Silicones and derivatives were the most common skin repair ingredients in medical devices (33%), followed by petrolatum and derivatives (22%) and alginate (15%). This work provides an overview of the most used skin repair ingredients, highlighting their different mechanisms of action, aiming to provide an up-to-date tool to support health professionals’ decisions.

The high cost of wound healing treatment, the slow recovery of wounds, and the uncertainty of being affected by the body's physiological activities constitute a serious burden on public health. In this work, we report the preparation and characterization of chitosan (CS), PVP, and dihydroquercetin (DHQ) nanofiber film used as wound excipients, as well as in vivo and in vitro evaluations, and verify that the film is effective in wounds. The results show that the prepared film has good morphology, thermal stability and hydrophilicity. In vitro studies have shown that it has antibacterial activity against S.aureus and E.coli , and the DPPH free radical scavenging rate proves that the fiber film has antioxidant activity. MTT cytotoxicity test proved that the film is non-toxic to Hacat cells. Animal experiments have proved that wounds treated with CS-PVP-DHQ nanofiber film heal faster. This article also studied the composite nanofiber film by inducing autophagy pathway and increasing the expression of pan-keratin, vascular endothelial growth factor VEGF and CD31 to promote wound healing. Therefore, the nanofiber film herein show great potential in wound healing applications. [ABSTRACT FROM AUTHOR]

Chronic wounds represent a major challenge to the present healthcare system. In recent decades, many topical therapies have been investigated for the treatment of chronic wounds, including different types of wound dressings, antimicrobial agents, and cell therapy. Platelet-derived growth factor (PDGF) plays an important role in wound healing and has been approved for treatment of wounds related to diabetes mellitus. However, the high cost and short retention time of PDGF protein have limited its wide application. To overcome this challenge, we designed a PDGF-mimicking peptide by connecting PDGF epitope VRKIEIVRKK and self-assembling motif derived from β-amyloid peptide. The resultant peptide can self-assemble into a fibril-rich network and leads to supramolecular hydrogelation with good stability. The hydrophilic epitope can be exposed on the surface of nanofibrils, which might contribute to the binding and activation of PDGF receptors. The forming hydrogel is able to induce the growth and migration of vascular endothelial cells and promote the formation of vascular branches. In the full-thickness skin wounds of healthy mice, after the application of the hydrogel, the density of neovascularization marked by CD31 was greater than that in the control group on Day 3. Larger collagen deposition and a thicker epidermis were observed on Day 12. These results demonstrate that the hydrogel can stimulate collagen deposition and angiogenesis, enhance skin regeneration, and show an excellent therapeutic effect. Taken together, this work not only provides new insight into the design of bioactive peptides but also offers a promising biomaterial for wound healing. [ABSTRACT FROM AUTHOR]

[Display omitted] The complex wound repair induced by tumor surgery and infection is still the clinical challenge due to the subsequent tumor recurrence and serious inflammation. Herein, we develop a bioactive Si-Ca-Sr glass-based therapy-regeneration-enabled nanohybrids (BSr@PPE) with hierarchical versatility for overcoming the challenges of tumor and infection-impaired wound repair. BSr@PPE showed a representative concentration-dependent photothermal effect, strong free radical scavenging and antibacterial ability, as well as good UV-shielding properties and high biocompatibility. BSr@PPE could efficiently kill tumor cells through the photothermal effect, show the robust antibacterial activity against normal and multi-drug resistant bacteria and enhance the fibroblasts migration in vitro. In vivo animal experiments suggested that BSr@PPE could effectively promote epithelial reconstruction, collagen deposition and angiogenesis in normal wounds, reduce inflammation and enhance repair in multi-drug bacterial infected wounds, accelerate the tumor-impaired wound through inhibit the tumor cells. This work may provide a new strategy and multifunctional bioactive material for treating the tissue repair and regeneration under the multi-pathological environments. [ABSTRACT FROM AUTHOR]

The repair of skin injury has always been a concern in the medical field. As a kind of biopolymer material with a special network structure and function, collagen-based hydrogel has been widely used in the field of skin injury repair. In this paper, the current research and application status of primal hydrogels in the field of skin repair in recent years are comprehensively reviewed. Starting from the structure and properties of collagen, the preparation, structural properties, and application of collagen-based hydrogels in skin injury repair are emphatically described. Meanwhile, the influences of collagen types, preparation methods, and crosslinking methods on the structural properties of hydrogels are emphatically discussed. The future and development of collagen-based hydrogels are prospected, which is expected to provide reference for the research and application of collagen-based hydrogels for skin repair in the future.

Introduction: Inspired by application of platelet-rich plasma (PRP) in skin treatment during injuries, an extracting method was developed here to recover high amounts of cytokines and growth factors from PRP; this prepared extract was named as self-growth colony (SGC). Methods: In optimization of SGC preparation, various parameters were tested, for example, centrifugation force, freeze-thaw, sonication, and inclusion of calcium chelator. The amounts of cytokines and growth factors, including platelet factor 4, ß-thromboglobulin, epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, were measured by ELISA assay. Results: By comparing to PRP, the prepared SGC contained a significant higher amount of measured growth factors. In addition, the degradation of growth factors within SGC during the storage was calibrated, which showed better stability as compared to that of PRP preparation. Having possible application in skin care, the optimized SGC was chemically standardized by using the enrichment of growth factors. Application of SGC in cultured keratinocytes stimulated the wound healing of injured cultures. In line to this notion, SGC was applied onto human skin, and thereafter the robust improvement of skin properties was revealed. Conclusions: The potential application of SGC in treating skin rejuvenation and ageing, as well as its elaborated application for medical purpose, that is, wound healing, was illustrated. [ABSTRACT FROM AUTHOR]

The skin is the largest organ in the body, fulfilling a variety of functions and acting as a barrier for internal organs against external insults. As for extensive or irreversible damage, skin autografts are often considered the gold standard, however inherent limitations highlight the need for alternative strategies. Engineering of human-compatible tissues is an interdisciplinary and active field of research, leading to the production of scaffolds and skin substitutes to guide repair and regeneration. However, faithful reproduction of extracellular matrix (ECM) architecture and bioactive content capable of cell-instructive and cell-responsive properties remains challenging. ECM is a heterogeneous, connective network composed of collagens, glycoproteins, proteoglycans, and small molecules. It is highly coordinated to provide the physical scaffolding, mechanical stability, and biochemical cues necessary for tissue morphogenesis and homeostasis. Decellularization processes have made it possible to isolate the ECM in its native and three-dimensional form from a cell-populated tissue for use in skin regeneration. In this review, we present recent knowledge about these decellularized biomaterials with the potential to be used as dermal or skin substitutes in clinical applications. We detail tissue sources and clinical indications with success rates and report the most effective decellularization methods compatible with clinical use. [ABSTRACT FROM AUTHOR]

The basic fibroblast growth factor (bFGF) plays an important role in the wound repair process. However, lacking of better biomaterials to carry bFGF still is a challenge in skin repair and regeneration. In this study, the human-like collagen (HLC) cross-linked with transglutaminase (TG) to fabricate a HLC/TG hydrogel to load bFGF. The physical properties of hydrogel, such as interior structure, mechanical property, were characterized in vitro using scanning electron microscopy (SEM), rheometer. Then, the effects of the HLC/TG hydrogel on the bFGF and cell attachmentwere evaluated, and the results showed that the HLC/TG hydrogel has good biocompatibility towards bFGF and cells. Finally, skin wound healing test was performed for the evaluation of HLC/TG hydrogels with bFGF in a mouse model. All results of macroscopic and microscopic analysis indicated that not only our HLC/TG hydrogel provide a delivery of growth factors, but also the HLC/TG hydrogel with bFGF achieving better skin regeneration in the structure and function. [ABSTRACT FROM AUTHOR]

To mimic the natural structure of tissue extracellular matrix, a novel silk fibroin (SF)/hyaluronic acid (HA)/sodium alginate (SA) composite scaffold (92% in porosity) was prepared by freeze-drying. Fourier-transform infrared spectroscopy and Raman spectra indicated interactions among SF, HA, and SA molecules. Scanning electron microscopy showed that the prepared SF/HA/SA scaffold had soft, elastic characteristics, with an average pore diameter of 93 μm. Mechanical property, thermogravimetric analyses and degradation results indicated that the SF/HA/SA scaffold had good physical stability in body fluid and mechanical movement-related environments. Cell proliferation, morphological, and live-dead analyses showed that NIH-3T3 fibroblast cells were better able to attach, grow, and proliferate on the SF/HA/SA scaffold compared with SF, SF/HA, and SF/SA scaffolds. We evaluated the wound healing effects in a rat full-thickness burn model. The hematoxylin-eosin (H&E) and Masson's trichrome staining results from SF/HA/SA scaffold showed that improved re-epithelialization, enhanced extracellular matrix remodeling. Our findings showed that the prepared SF/HA/SA scaffold can provide a potential way as a wound dressing for skin repair. [ABSTRACT FROM AUTHOR]

Wound healing is a physiological restorative response to tissue and cell injury. This process occurs in collaboration with a complex cascade of cellular events, including biochemical alterations to the extracellular matrix. Polydeoxyribonucleotide (PDRN) is a fragmented DNA mixture from Oncorhynchus mykiss or Oncorhynchus keta sperm known to promote tissue regeneration under different pathophysiological conditions. However, the most effective molecular size of PDRNs for promoting the wound healing process and quality has not been established. In the present study, the regeneration quality with low (<50 kDa), middle [classic PDRN; 50–1,500 kDa] and high (>1,500 kDa) molecular weight PDRNs in a skin wound healing mouse model was examined using hematoxylin and eosin, as well as Masson's trichrome stain. A 4 mm biopsy punch was used to produce wounds in the skin of the mice. PDRN-mediated cellular behavior and signaling were evaluated by in vitro scratch assay and western blot analysis, respectively. It was observed that the apparent surface wound healing processes were not significantly different between PDRN molecular sizes. Immunohistochemical analysis revealed that classic PDRN-injected mice exhibited less lipid accumulation with increased collagen composition. These results suggested that 50–1,500 kDa PDRN offers an effective DNA mixture to improve wound healing quality. Furthermore, classic PDRN increased cell migration via c-Jun N-terminal kinase signaling in human fibroblasts. The present study suggests an optimal PDRN molecular weight to promote wound healing, and novel approaches for therapeutic strategies to improve tissue regeneration quality. [ABSTRACT FROM AUTHOR]

Polysaccharides, being a natural, active, and biodegradable polymer, have garnered significant attention due to their exceptional properties. These properties make them ideal for creating multifunctional hydrogels that can be used as wound dressings for skin injuries. Polysaccharide hydrogel has the ability to both simulate the natural extracellular matrix, promote cell proliferation, and provide a suitable environment for wound healing while protecting it from bacterial invasion. Polysaccharide hydrogels offer a promising solution for repairing damaged skin. This review provides an overview of the mechanisms involved in skin damage repair and emphasizes the potential of polysaccharide hydrogels in this regard. For different skin injuries, polysaccharide hydrogels can play a role in promoting wound healing. However, we still need to conduct more research on polysaccharide hydrogels to provide more possibilities for skin damage repair. [ABSTRACT FROM AUTHOR]

The skin is the largest organ in the body, fulfilling a variety of functions and acting as a barrier for internal organs against external insults. As for extensive or irreversible damage, skin autografts are often considered the gold standard, however inherent limitations highlight the need for alternative strategies. Engineering of human-compatible tissues is an interdisciplinary and active field of research, leading to the production of scaffolds and skin substitutes to guide repair and regeneration. However, faithful reproduction of extracellular matrix (ECM) architecture and bioactive content capable of cell-instructive and cell-responsive properties remains challenging. ECM is a heterogeneous, connective network composed of collagens, glycoproteins, proteoglycans, and small molecules. It is highly coordinated to provide the physical scaffolding, mechanical stability, and biochemical cues necessary for tissue morphogenesis and homeostasis. Decellularization processes have made it possible to isolate the ECM in its native and three-dimensional form from a cell-populated tissue for use in skin regeneration. In this review, we present recent knowledge about these decellularized biomaterials with the potential to be used as dermal or skin substitutes in clinical applications. We detail tissue sources and clinical indications with success rates and report the most effective decellularization methods compatible with clinical use.

Selective estrogen receptor modulators (SERMs) have been developed to achieve beneficial effects of estrogens while minimizing their side effects. In this context, we decided to evaluate the protective effect of genistein, a natural SERM, on skin flap viability in rats and in a series of in vitro experiments on endothelial cells (migration, proliferation, antioxidant properties, and gene expression profiling following genistein treatment). Our results showed that administration of genistein increased skin flap viability, but importantly, the difference is only significant when treatment is started 3 days prior the flap surgery. Based on our in vitro experiments, it may be hypothesized that the underlying mechanism may rather by mediated by increasing SOD activity and Bcl-2 expression. The gene expression profiling further revealed 9 up-regulated genes (angiogenesis/inflammation promoting: CTGF, CXCL5, IL-6, ITGB3, MMP-14, and VEGF-A; angiogenesis inhibiting: COL18A1, TIMP-2, and TIMP-3). In conclusion, we observed a protective effect of genistein on skin flap viability which could be potentially applied in plastic surgery to women undergoing a reconstructive and/or plastic intervention. Nevertheless, further research is needed to explain the exact underlying mechanism and to find the optimal treatment protocol. [ABSTRACT FROM AUTHOR]