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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. [ABSTRACT FROM AUTHOR]

Fibroblasts are typical mesenchymal cells widely distributed throughout the human body where they (1) synthesise and maintain the extracellular matrix, ensuring the structural role of soft connective tissues; (2) secrete cytokines and growth factors; (3) communicate with each other and with other cell types, acting as signalling source for stem cell niches; and (4) are involved in tissue remodelling, wound healing, fibrosis, and cancer. This review focuses on the developmental heterogeneity of dermal fibroblasts, on their ability to sense changes in biomechanical properties of the surrounding extracellular matrix, and on their role in aging, in skin repair, in pathologic conditions and in tumour development. Moreover, we describe the use of fibroblasts in different models (e.g., in vivo animal models and in vitro systems from 2D to 6D cultures) for tissue bioengineering and the informative potential of high-throughput assays for the study of fibroblasts under different disease contexts for personalized healthcare and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the anti-aging and skin repair effects of madecassoside (MA) on D-galactose-induced skin aging mice. Mice were divided into 6 groups (n=12) : normal group (N), model group (M), low, medium, high-dose MA groups (L-MA, M-MA, H-MA) and high-dose MA+Nrf2 inhibitor ML385 group (H-MA+ML385). The body weight, skin water content, antioxidant indicators ( SOD, CAT, GSH-Px and MDA ), HYP and HA levels in skin tissue of mice in each group were detected. Skin histology was evaluated by HE staining. The transcript levels of MMP-1, MMP-3, Nrf2, Keapl and HO-1 in skin tissues were detected by RT-qPCR. The protein expression levels of Nrf2, Keapl and HO-1 in skin tissue were detected by Western blotting. The results show that compared with the M group, the skin water content of mice in L-MA group, M-MA group and H-MA group increases, the thickness of the epidermis and dermis increases, the skin structure is significantly improved, the levels of SOD, CAT and GSH-Px increase, the level of MDA decreases, the level of HYP and HA increases, the relative expression of MMP-1 and MMP-3 mRNA decreases, the relative expression of Nrf2 and HO-1 mRNA and protein increases, and the relative expression of Keapl mRNA and protein decrease ( P<0.05). ML385 partially weakens the activation effect of MA on the Nrf2-HO-1 pathway, and weakens the anti-aging and skin repair effects of MA (P<0.05). This study shows that MA has good anti-aging and skin repair effects, and its mechanism is related to the activation of Nrf2-HO-1 pathway. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is marked by impaired skin barrier function and persistent pruritus. It significantly deteriorates patients' quality of life, making it one of the most burdensome non-lethal skin disorders. Filaggrin plays a crucial role in the pathophysiology of barrier disruption in AD, interacting with inflammatory mediators. It is an integral part of the extracellular matrix architecture, serving to protect the skin barrier and attenuate the inflammatory cascade. In this study, we engineered a novel recombinant human filaggrin (rhFLA-10) expression vector, which was subsequently synthesized and purified. In vitro and ex vivo efficacy experiments were conducted for AD. rhFLA-10, at low concentrations (5 to 20 μg/mL), was non-toxic to HACaT cells, significantly inhibited the degranulation of P815 mast cells, and was readily absorbed by cells, thereby exerting a soothing therapeutic effect. Furthermore, rhFLA-10 demonstrated anti-inflammatory properties (p < 0.05). In vivo, efficacy experiments further substantiated that rhFLA-10 could effectively ameliorate AD in mice and facilitate the repair of damaged skin (p < 0.001). These findings underscore the considerable potential of rhFLA-10 in the treatment of AD. [ABSTRACT FROM AUTHOR]

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.

Stretch marks are far from exclusively appearing on pregnant women and appear whenever the body experiences rapid growth. Collagen fibres are altered in the dermis, which is associated with a loss of orientation, and the elastic network is disrupted, leading to a fibrotic organisation. This results in epidermal tearing that produces skin lesions. Centella asiatica (CAST) is a well-known medicinal plant rich in active triterpenic molecules and traditionally used to treat wounds and help skin repair. The aim of this study was to evaluate CAST extract as a natural way to solve stretch mark concerns and understand its mechanism of action. Fibroblast proliferation based on scratch assay model and their gene expression by RT-qPCR was first evaluated. At the ex vivo level, elastin fibres were quantified by immunofluorescence. The orientation of the collagen fibres and their occupation of the dermis were analysed after Sirius red staining and specific software analysis. We showed that CAST stimulated fibroblast proliferation and reduced extracellular matrix degradation and fibrosis. On a stretch-marked skin explant, CAST increased the occupation of collagen fibres and elastin production. Based on the mechanisms behind the formation of stretch marks, CAST restored the dermis network by optimising fibre organisation for a visible skin remodelling effect. [ABSTRACT FROM AUTHOR]

Introduction: Previously, we achieved large-scale expansion of bone marrowderived suppressor cells (MDSCs) derived from cluster of differentiation (CD)34+ cells cultured in human umbilical cord blood (hUCB) and demonstrated their immunomodulatory properties. In the present study, we assessed the therapeutic efficacy of hUCB-MDSCs in atopic dermatitis (AD). Methods: Dermatophagoides farinae (Df)-induced NC/Nga mice (clinical score of 7) were treated with hUCB-MDSCs or a control drug. The mechanisms underlying the therapeutic effects of hUCB-MDSCs were evaluated. Results and discussion: hUCB-MDSCs demonstrated immunosuppressive effects in both human and mouse CD4+ T cells. hUCB-MDSCs significantly reduced the clinical severity scores, which were associated with histopathological changes, and reduced inflammatory cell infiltration, epidermal hyperplasia, and fibrosis. Furthermore, hUCB-MDSCs decreased the serum levels of immunoglobulin E, interleukin (IL)-4, IL-5, IL-13, IL-17, thymus- and activation-regulated chemokines, and thymic stromal lymphopoietin. Additionally, they altered the expression of the skin barrier function-related proteins filaggrin, involucrin, loricrin, cytokeratin 10, and cytokeratin 14 and suppressed the activation of Df-restimulated T-cells via cell-cell interactions. hUCB-MDSCs promoted skin recovery and maintained their therapeutic effect even after recurrence. Consequently, hUCB-MDSC administration improved Df-induced AD-like skin lesions and restored skin barrier function. Our findings support the potential of hUCB-MDSCs as a novel treatment strategy for AD. [ABSTRACT FROM AUTHOR]

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]

Fibroblasts are typical mesenchymal cells widely distributed throughout the human body where they (1) synthesise and maintain the extracellular matrix, ensuring the structural role of soft connective tissues; (2) secrete cytokines and growth factors; (3) communicate with each other and with other cell types, acting as signalling source for stem cell niches; and (4) are involved in tissue remodelling, wound healing, fibrosis, and cancer. This review focuses on the developmental heterogeneity of dermal fibroblasts, on their ability to sense changes in biomechanical properties of the surrounding extracellular matrix, and on their role in aging, in skin repair, in pathologic conditions and in tumour development. Moreover, we describe the use of fibroblasts in different models (e.g., in vivo animal models and in vitro systems from 2D to 6D cultures) for tissue bioengineering and the informative potential of high-throughput assays for the study of fibroblasts under different disease contexts for personalized healthcare and regenerative medicine applications.

The skin is the largest organ of the human body, and its structural integrity plays a crucial role in the maintenance of the normal physiological function of the human body. The repair of large skin trauma and the healing of chronic skin ulcers are clinical problems to be solved. Although great progress has been made in the field of skin tissue engineering over the last decades, it is still a challenge to develop the engineered skin by incorporating with skin appendages, such as hair follicles, sweat glands, sebaceous glands and vascularization. However, 3D bio-printing technology provides a potential to solve these problems. In this review, we briefly discuss the application, prospective, and challenges of 3D bio-printing technology in skin wound repair.

Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is marked by impaired skin barrier function and persistent pruritus. It significantly deteriorates patients’ quality of life, making it one of the most burdensome non-lethal skin disorders. Filaggrin plays a crucial role in the pathophysiology of barrier disruption in AD, interacting with inflammatory mediators. It is an integral part of the extracellular matrix architecture, serving to protect the skin barrier and attenuate the inflammatory cascade. In this study, we engineered a novel recombinant human filaggrin (rhFLA-10) expression vector, which was subsequently synthesized and purified. In vitro and ex vivo efficacy experiments were conducted for AD. rhFLA-10, at low concentrations (5 to 20 μg/mL), was non-toxic to HACaT cells, significantly inhibited the degranulation of P815 mast cells, and was readily absorbed by cells, thereby exerting a soothing therapeutic effect. Furthermore, rhFLA-10 demonstrated anti-inflammatory properties (p < 0.05). In vivo, efficacy experiments further substantiated that rhFLA-10 could effectively ameliorate AD in mice and facilitate the repair of damaged skin (p < 0.001). These findings underscore the considerable potential of rhFLA-10 in the treatment of AD.

The skin is the largest organ of the human body, and its structural integrity plays a crucial role in the maintenance of the normal physiological function of the human body. The repair of large skin trauma and the healing of chronic skin ulcers are clinical problems to be solved. Although great progress has been made in the field of skin tissue engineering over the last decades, it is still a challenge to develop the engineered skin by incorporating with skin appendages, such as hair follicles, sweat glands, sebaceous glands and vascularization. However, 3D bio-printing technology provides a potential to solve these problems. In this review, we briefly discuss the application, prospective, and challenges of 3D bio-printing technology in skin wound repair. [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. [ABSTRACT FROM AUTHOR]

Objective: The biological safety of natural jade materials and assembled jade‐activated materials on cells and their anti‐inflammatory and damage repair functions, as well as the repair function on sensitive skin, were studied utilizing in vitro cell biology and in vivo. Methods: Human skin fibroblasts were used as model cells to conduct cytotoxicity experiments in vitro, and the effects on the expression of inflammatory factors and growth factor‐related genes in fibroblasts were explored. The gene expression values of inflammatory factors IL‐1, IL‐6, TNF‐α and cytokines epidermal growth factors, fibroblast growth factors and COL1A1 in fibroblasts were measured by polymerase chain reaction test. Thirty women with sensitive skin were selected to apply a mask containing jade extract three times a week. After two weeks, non‐invasive measures related to skin sensitivity were tested. Results: We confirmed the presence of anti‐inflammatory effects in both jade materials, with the effects of the assembled activated jade material being superior to that of the natural jade material. Jade extracts significantly increased the gene expressions of EGF, FGF and COL1A1 in HDF. The results of the in vivo study showed that the mask containing jade extract could significantly increase the skin hydration and decrease the rate of transepidermal water loss and skin lactic acid sting test scores after two weeks of use. Subjective evaluations confirmed improvements in skin dryness, smoothness and fineness. No new sensitization occurred in subjects, and the product was non‐irritating. No adverse skin reactions were observed during the test. Conclusions: The jade materials were able to downregulate the expression of inflammatory factor genes, up‐regulate the expression of growth factor genes, and improve the anti‐inflammation and repair ability of skin. Furthermore, the test results of participants with sensitive skin after using the mask containing jade extract showed that the mask has repairing ability. [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]

Combined methods of applying chemical peels and antioxidants could be an option for skin rejuvenation with no down-time. The penetration of active substances can be enhanced by microneedle mesotherapy. The study was conducted on a group of 20 female volunteers, aged 40–65 years. All volunteers received a series of eight treatments performed every seven days. The whole face was first treated with azelaic acid; following this, the right side received a 40% solution of vitamin C and the left side 10% vitamin C with microneedling. Hydration and skin elasticity were markedly improved, with better results observed on the microneedling side. Melanin and erythema index decreased. No significant side effects were seen. The combination of active ingredients and delivery techniques have great potential to enhance the effectiveness of cosmetic preparations, probably by multidirectional ways of action. In our study, we demonstrated that both 20% azelaic acid + 40% vitamin C treatment and 20% azelaic acid + 10% vitamin C + microneedle mesotherapy efficiently improved the assessed parameters of aging skin. However, the use of microneedling mesotherapy as a means of direct delivery of active compound to the dermis enhanced the effectiveness of the studied preparation. [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.

In recent years, hydrogel microsphere has attracted much attention due to its great potential in the field of skin repair. This paper reviewed the recent progress in the preparation strategy of hydrogel microsphere and its application in skin repair. In this review, several preparation methods of hydrogel microsphere were summarized in detail. In addition, the related research progress of hydrogel microspheres for skin repair was reviewed, and focused on the application of bioactive microspheres, antibacterial microspheres, hemostatic microspheres, and hydrogel microspheres as delivery platforms (hydrogel microspheres as a microcarrier of drugs, bioactive factors, or cells) in the field of skin repair. Finally, the limitations and future prospects of the development of hydrogel microspheres and its application in the field of skin repair were presented. It is hoped that this review can provide a valuable reference for the development of the preparation strategy of hydrogel microspheres and promote the application of hydrogel microspheres in skin repair.

Stretch marks are far from exclusively appearing on pregnant women and appear whenever the body experiences rapid growth. Collagen fibres are altered in the dermis, which is associated with a loss of orientation, and the elastic network is disrupted, leading to a fibrotic organisation. This results in epidermal tearing that produces skin lesions. Centella asiatica (CAST) is a well-known medicinal plant rich in active triterpenic molecules and traditionally used to treat wounds and help skin repair. The aim of this study was to evaluate CAST extract as a natural way to solve stretch mark concerns and understand its mechanism of action. Fibroblast proliferation based on scratch assay model and their gene expression by RT-qPCR was first evaluated. At the ex vivo level, elastin fibres were quantified by immunofluorescence. The orientation of the collagen fibres and their occupation of the dermis were analysed after Sirius red staining and specific software analysis. We showed that CAST stimulated fibroblast proliferation and reduced extracellular matrix degradation and fibrosis. On a stretch-marked skin explant, CAST increased the occupation of collagen fibres and elastin production. Based on the mechanisms behind the formation of stretch marks, CAST restored the dermis network by optimising fibre organisation for a visible skin remodelling effect.

Kinkéliba (Combretum micranthum, Seh-Haw in Wolof) is a popular bush tea in West African countries. Although the kinkéliba plant's leaves have been widely consumed for its nutritional and medicinal properties, its benefits on skin health potential have been practically untouched. In human epidermal primary keratinocytes, vitexin and isovitexin-rich kinkéliba extract treatment significantly (p < 0.001) enhanced up to 39.6% of the cell survival rate decreased by UV radiation irritation. The treatment of kinkéliba leaf extracts also reduced the production of UV-induced pro-inflammatory cytokines IL-6 and IL-8 by 57.6% and 42.5%, respectively (p < 0.001), which cause skin redness and skin barrier dysfunction, as well as wrinkles and collagen degradation. The anti-inflammation efficacy of kinkéliba leaf extracts might involve significant inhibition on the levels of cellular reactive oxygen species (ROS) (−70.8%, p < 0.001) and nitrotyrosine (−56.9%, p < 0.05). Further topical applications of kinkéliba leaf extract gel were found to reduce sodium lauryl sulfate (SLS)-induced skin inflammation: at D7, the skin trans-epidermal water loss (TEWL) and skin redness (a* value) were both reduced by 59.81% (p < 0.001) and 22.4% (p < 0.001), compared with D0. In vitro and in vivo data support a new topical application of the kinkéliba leaf as an effective active ingredient for the treatment of skin inflammation, as well as subsequent barrier dysfunction and inflammaging. [ABSTRACT FROM AUTHOR]

Abstract 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.

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]

Nuclear and radiological accidents can occur due to poor management, in transportation, radiation therapy and nuclear wards in hospitals, leading to extreme radiation exposure and serious consequences for human health. Additionally, in many of previous radiological accidents, skin damage was observed in patients and survivors due to the high radiation exposure. However, as part of a medical countermeasures in a nuclear/radiological emergency, it is critical to plan for the treatment of radiation-induced skin damage. Hence, the new, non-invasive technology of photodynamic therapy (PDT) is projected to be more effectively used for treating skin damage caused by high-dose radiation. PDT plays an important role in treating, repairing skin damage and promoting wound healing as evidenced by research. This review, highlighted and recommended potential impacts of PDT to repair and decrease radiation-induced skin tissue damage. Moreover, we have suggested some photosensitizer (PS) agent as radio-mitigator drugs to decrease radiobiological effects. [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.

Hydrogels based on various polymeric materials have been successfully developed in recent years for a variety of skin applications. Several studies have shown that hydrogels with regenerative, antibacterial, and antiinflammatory properties can provide faster and better healing outcomes, particularly in chronic diseases where the normal physiological healing process is significantly hampered. Various experimental tests are typically performed to assess these materials' ability to promote angiogenesis, re-epithelialization, and the production and maturation of new extracellular matrix. Immunohistochemistry is important in this context because it allows for the visualization of in situ target tissue factors involved in the various stages of wound healing using antibodies labelled with specific markers detectable with different microscopy techniques. This review provides an overview of the various immunohistochemical techniques that have been used in recent years to investigate the efficacy of various types of hydrogels in assisting skin healing processes. The large number of scientific articles published demonstrates immunohistochemistry's significant contribution to the development of engineered biomaterials suitable for treating skin injuries.

In this study, a hydrogel composite wound dressing with antibacterial and self-healing ability was prepared using cysteine-modified carboxymethyl chitosan, sodium oxidized alginate, and but-3-yn-2-one base on Schiff base and thiol-alkynone double cross-links. The structure and properties of the hydrogel were characterized by scanning electron microscope, Fourier-transform infrared, and rheological test, followed by antibacterial and in vivo biocompatibility tests. The results showed that the hydrogel exhibited good self-healing, mechanical properties, good antibacterial effect, and in vivo biocompatibility, and can inhibit inflammation and promote skin tissue regeneration in mice. This novel self-healing hydrogel dressing has a broad application prospect in skin tissue engineering. [ABSTRACT FROM AUTHOR]

Porcine placenta extract (PPE) contains many water-soluble macromolecular compounds, such as proteins and growth factors, which have limited transportation through the skin. This study aimed to assess the effect of porcine-placenta-extract (PPE)-loaded nano-transdermal systems for skin repair and hair growth promotion. The potentials of the nanoformulation for cytotoxicity, cell proliferation, intracellular reactive oxygen species (ROS) reduction, lipoxygenase inhibition, intracellular inflammatory cytokine reduction, and cell aggregation were evaluated. PPE-entrapped niosome nanovesicles were produced by thin-film hydration and probe-sonication methods, followed by incorporation in a skin serum formulation. The physicochemical properties of the formulation were examined, and the efficacy of the serum formulation was elucidated in humans. The results showed that PPE had no toxicity and was able to induce cell growth and cell aggregation. In addition, PPE significantly decreased intracellular ROS, inhibited lipoxygenase activity, and reduced the production of intracellular tumor necrosis factor-α. In the in vivo human study, the PPE nanovesicles-loaded serum could improve skin properties by increasing skin hydration. Moreover, it was capable of promoting hair growth by increasing hair elongation and melanin index after application for one month. Consequently, the PPE nanovesicles-loaded serum was effective for skin anti-aging and hair rejuvenation. [ABSTRACT FROM AUTHOR]

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]

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Postoperative infection caused by bacteria and limited amounts of regenerated tissue are important factors affecting the efficacy of guided tissue regeneration (GTR). However, a simple GTR membrane functions only as a mechanical barrier for isolation and lacks the ability to resist bacteria and actively induce tissue regeneration. In this study, an ornidazole (ONZ)/basic fibroblast growth factor (bFGF)-loaded poly(lactic-co-glycolic acid) (PLGA)/wool keratin (WK) composite membrane with a core/shell structure was prepared by emulsion electrospinning. ONZ was used in the shell layer to inhibit bacteria and bFGF in the core layer to accelerate tissue regeneration. The ONZ/bFGF composite membrane, with early substantial release of ONZ within 7 days and slow sustained release of bFGF for more than 28 days, exhibited good cell barrier function, cytocompatibility and degradability, and inhibited the proliferation of Pg, Fn and Pa over 21 days. Moreover, this composite membrane facilitated periodontal tissue regeneration and rapid wound healing. The ONZ/bFGF-loaded composite membrane is a strong candidate as a GTR membrane for periodontal tissue regeneration, and it also holds great potential as a functional dressing for skin defect repair. These results will broaden the prospects for the construction and application of multifunctional tissue engineering scaffolds for sustained drug release.

Abstract 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.

Background: Amino acids are major components of skin's natural moisturizing factors and play a role in regulating skin hydration and skin pH. Objective: This research examines a proprietary amino acid complex technology (AAComplex) designed to help reduce skin irritation and repair skin damage. Methods: In‐ vitro Scratch Assay HaCaT cells are scratched, and the wounds are imaged at different time points until the closure of the scratch wound is detected. In‐vitro 3D Reconstructed Human Tissue Evaluation The concentration of heat shock protein 27 (HSP‐27) extracted from 3D reconstructed human skin equivalent tissues and IL‐1a released to the media was determined using enzyme‐linked immunosorbent assays. In Vivo Clinical Study 37 subjects were enrolled in a split‐face study design. On test days 1, 2, 4, and 8, subjects visited the test facility to have their face assessed by facial swabbing and bio‐instrumentation measurements. Results: In‐ vitro Scratch Assay The AAComplex demonstrated a strong cell renewal benefit in the HaCaT (human) cells scratch assay. In Vitro 3D Reconstructed Human Tissue Evaluation AAComplex demonstrated a significant skin repair benefit by quantifying Heat Shock Protein, HSP‐27. Induced skin irritation was significantly reduced by quantifying interleukin‐1 alpha biomarker, IL‐1a. In Vivo Clinical Study The test products delivered skin benefits by reducing visual redness and skin irritation while increasing moisturization. Conclusion: The in vitro and in vivo clinical studies demonstrated that the AAComplex technology formulated in the commercially available Skin Recovery System effectively reduced skin irritation and redness as well as accelerating the skin repair process. [ABSTRACT FROM AUTHOR]

Skin disorders are widespread around the world, affecting people of all ages, and oxidative stress represents one of the main causes of alteration in the normal physiological parameters of skin cells. In this work, we combined a natural protein, fibroin, with antioxidant compounds extracted in water from pomegranate waste. We demonstrate the effective and facile fabrication of bioactive and eco-sustainable films of potential interest for skin repair. The blended films are visually transparent (around 90%); flexible; stable in physiological conditions and in the presence of trypsin for 12 days; able to release the bioactive compounds in a controlled manner; based on Fickian diffusion; and biocompatible towards the main skin cells, keratinocytes and fibroblasts. Furthermore, reactive oxygen species (ROS) production tests demonstrated the high capacity of our films to reduce the oxidative stress induced in cells, which is responsible for various skin diseases. [ABSTRACT FROM AUTHOR]

Objective: Propolis has been used since antiquity, but recent reports of its biological properties hint that it could be employed as a topical pharmaceutical and cosmetic ingredient. This work aims to probe the action of Portuguese propolis extracts on skin cells, providing mechanistic insights into its mode of action and preliminarily assessing its applicability as a skin repair ingredient. Methods: The total phenolic content of propolis extracts was measured by the Folin Ciocalteu method. The cytotoxic effect of propolis extracts in human keratinocytes was determined and non‐cytotoxic concentrations of the extracts were used to study the impact on collective cell migration, cell cycle and intracellular ROS levels. Results: o significant impact was observed in collective cell migration, but one of the extracts mildly increased G2 phase while reducing the % of sub‐G1 at a non‐cytotoxic concentration. The two extracts with higher phenolic content strongly prevented intracellular cellular ROS accumulation upon exposure to TBHP. Collectively, these results indicate that the putative beneficial effects of propolis extracts in skin repair may not be attributable to induction of collective cell migration but could be partially ascribed to the protection from oxidative stress, which could act in synergy with its well‐known antimicrobial activity. Conclusion: These data support the applicability of this material in topical and cosmetic formulations and further in vivo assays should be conducted to fully characterize its efficacy and safety. [ABSTRACT FROM AUTHOR]

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. Wounds and ulcers, especially burn wounds, are major causes of morbidity and mortality and pose a significant burden for individuals and societies. The skin has numerous structures that play important roles in wound healing via cells and growth factors. Tissue engineering and regenerative medicine represent a rather new field that focuses on manipulating cells and growth factors, aiming to facilitate repair and regeneration of injured tissues and organs. This review focuses on different burn injuries that can result in nonhealing wounds, provides an overview of several cells and growth factors that are involved in the healing process of the skin and introduces various strategies practiced in tissue engineering with regard to cutaneous wound healing. [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]

Xilin Liu,* Da Huo,* Guangzhi Wu Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangzhi Wu Tel +86-13944181019Email wuguangzhi@jlu.edu.cnBackground/Purpose: Anterolateral thigh perforator (ALTP) flap and deep inferior epigastric perforator (DIEP) flap have been advantageous over traditional myocutaneous flaps as they preserve the integrity of donor site muscles and minimize the damage and complication to donor site structures. Here, we reported the efficacy of free ALTP and DIEP in the repair of large skin area and soft tissue defects on both lower limbs after trauma.Case Report: A 19-year-old female traffic accident victim presented with multiple open bilateral fractures to the lower extremities with joint dislocation, massive skin and soft tissue defects, and multiple soft tissue contusion. Wounds on both lower extremities were covered with VSD (Vacuum Sealing Drainage). The tibiofibular and ankle joints on both lower limbs were fixed using external fixators. DIEP and ALTP flap were performed at different times.Results: After transfer, the vascular pedicle was anastomosed to the anterior tibial artery, posterior tibial artery, and the accompanying vein. After the operation, the donor site was directly closed and sutured. All flaps survived with a good appearance, leaving only a linear scar at the donor site.Conclusion: This case shows that free ALTP and DIEP flaps are ideal for repairing large skin area and soft tissue defects in bilateral lower limbs after trauma.Keywords: anterolateral thigh perforator flap, deep inferior epigastric perforator flap, soft tissue repair, skin repair