Skin Wound Healing Process Research Articles

Arginine-Biofunctionalized Ternary Hydrogel Scaffolds of Carboxymethyl Cellulose–Chitosan–Polyvinyl Alcohol to Deliver Cell Therapy for Wound Healing

Wound healing is important for skin after deep injuries or burns, which can lead to hospitalization, long-term morbidity, and mortality. In this field, tissue-engineered skin substitutes have therapy potential to assist in the treatment of acute and chronic skin wounds, where many requirements are still unmet. Hence, in this study, a novel type of biocompatible ternary polymer hybrid hydrogel scaffold was designed and produced through an entirely eco-friendly aqueous process composed of carboxymethyl cellulose, chitosan, and polyvinyl alcohol and chemically cross-linked by citric acid, forming three-dimensional (3D) matrices, which were biofunctionalized with L-arginine (L-Arg) to enhance cellular adhesion. They were applied as bilayer skin biomimetic substitutes based on human-derived cell cultures of fibroblasts and keratinocytes were seeded and grown into their 3D porous structures, producing cell-based bio-responsive hybrid hydrogel scaffolds to assist the wound healing process. The results demonstrated that hydrophilic hybrid cross-linked networks were formed via esterification reactions with the 3D porous microarchitecture promoted by foam templating and freeze-drying. These hybrids presented chemical stability, physicochemical properties, high moisture adsorption capacity, surface properties, and a highly interconnected 3D porous structure well suited for use as a skin substitute in wound healing. Additionally, the surface biofunctionalization of these 3D hydrogel scaffolds with L-arginine through amide bonds had significantly enhanced cellular attachment and proliferation of fibroblast and keratinocyte cultures. Hence, the in vivo results using Hairless mouse models (an immunocompromised strain) confirmed that these responsive bio-hybrid hydrogel scaffolds possess hemocompatibility, bioadhesion, biocompatibility, adhesiveness, biodegradability, and non-inflammatory behavior and are capable of assisting the skin wound healing process.

A triple-mode strategy combining low-temperature photothermal, photodynamic, and chemodynamic therapies for treating infectious skin wounds.

The skin is the first natural barrier of the human body. Bacterial infections severely hinder the healing process of skin wounds and pose a great threat to human health. Therefore, it is particularly urgent to develop new antimicrobial strategies for bacterial pathogen clearance and wound healing. In this study, a metal-organic framework (MOF), Fe-MIL88B-NH2, was incorporated with the photosensitizer indocyanine green (ICG) to construct composite nanoparticles (MOF@ICG NPs) with multiple antibacterial activities. Under mild near-infrared (NIR) irradiation, the photosensitizer ICG in the MOF@ICG NPs undergoes photothermal conversion (∼45 °C) and photodynamic reactions to generate heat and singlet oxygen (1O2). In addition, the Fenton reaction of the NPs with hydrogen peroxide (H2O2) in the bacterial infection microenvironment resulted in the generation of hydroxyl radicals (˙OH), thus achieving the three-mode combination of low-temperature photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT). The in vitro experimental results showed that MOF@ICG MPs had excellent antibacterial properties and good cytocompatibility, with some ability to promote the migration of L-929 fibroblasts. Furthermore, under NIR irradiation, MOF@ICG NPs could significantly kill bacteria and promote skin wound healing according to the results of animal experiments. The wound healing rate reached 87.1% after 7 days of treatment. The research results break through the limitations of single-mode antibacterial technology and provide certain theoretical guidance and technical support for the research and development of new antibacterial materials.

The supplementation of mannan oligosaccharide in diet promotes the skin wound healing of juvenile turbot, Scophthalmus maximus

A 30-day feeding trial was conducted to investigate the effects of the supplementation of mannan oligosaccharide (MOS) in the diet on the skin wound healing process of juvenile turbot (Scophthalmus maximus). Two groups of diets were formulated, the control diet (CON) and the control diet supplemented with 0.16 % MOS (MOS), which were fed to the turbot separately. Each group had 3 replicates, with 20 fish per replicate. At the end of the feeding trial, all the fish were weighed and counted. Then four fish per tank were randomly selected for sampling, and the skin of the rest fish was wounded by a biopsy punch. The wounded fish continued to be fed as usual with the same diets respectively, and then sampled again at the 1, 3, and 7 day(s) post wounding (dpw). The results by image analysis showed that the wound closure rate of wounded fish was significantly improved by the supplementation of dietary MOS. As for the results of gene expression, dietary MOS promoted the expression of pro-inflammatory factors (il-1β &tnf-α) and decreased the expression of anti-inflammatory factors (tgf-β1 &il-10). It also enhanced the expression of genes related to re-epithelialization (mmp-9, fgf2, tgf-β1, rock1), as well as new tissue formation and remodeling (fn1, lamb2, col1-α, vegf). Furthermore, dietary MOS promoted re-epithelialization, cell proliferation, collagen deposition, and angiogenesis according to the histomorphological observation. In addition, the supplementation of MOS modified the communities of skin microbiota, decreasing the abundance of Rolstonia, Pseudomonas, and Aeromonas, while increasing the abundance of Pseudoalteromonas luteoviolacea and Shewanella colwellianav. In conclusion, the supplementation of dietary MOS (0.16 %) can promote the re-epithelialization and the recruitment of inflammatory cells, stimulate ECM biosynthesis and angiogenesis, modify the communities of skin microbiota, and ultimately promote the skin wound healing process.

SPRR1B+ keratinocytes prime oral mucosa for rapid wound healing via STAT3 activation

Oral mucosal wounds exhibit accelerated healing with reduced scarring compared to cutaneous wounds, representing an optimal wound healing paradigm. However, the specific cellular subtypes orchestrating the efficient healing of mucosal tissues remain elusive. Through a comprehensive analysis integrating bulk-mRNA and single-cell sequencing data during the wound healing process in oral mucosa and skin, we have delineated a distinct set of genes markedly upregulated during tissue repair. This collection of wound healing-associated genesets was highly enriched in a specific keratinocyte subpopulation identified as STAT3-activated SPRR1B+ keratinocytes. Notably, despite the inherent rapidity of oral mucosal healing, the induction of SPRR1B+ keratinocytes is evident in both skin and mucosal wound healing processes in murine model. Intriguingly, these wound healing-promoting SPRR1B+ keratinocytes, which are induced via STAT3 activation, inherently abundant in unwounded normal mucosa but absent in normal skin. SPRR1B knockdown significantly inhibits mucosal keratinocyte migration, a critical attribute for effective wound healing. In summary, through analysis of human oral and skin wound healing processes at single-cell resolution, coupled with validation in murine model, suggests STAT3-activated SPRR1B+ keratinocytes are associated with the rapid mucosal repair process. This discovery underscores the potential application of SPRR1B+ keratinocytes in the therapeutic management of chronic or non-healing wounds.

Comparing Line-Field Confocal Optical Coherence Tomography and Reflectance Confocal Microscopy on the In Vivo Healing Process of Lesions Induced by Fractional Photothermolysis.

The advent of ablative fractional photothermolysis has revolutionized laser dermatology by providing a method to produce well-standardized, precise, and repeatable microscopic lesions. These wounds typically heal within 1-3 weeks, depending on the body site, with a minimal risk of permanent scarring. This positions ablative fractional photothermolysis as an exemplary in vivo model for studying the skin's wound healing processes. This study aims to evaluate and compare the effectiveness of two noninvasive imaging techniques, reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT), in assessing skin wound healing following microscopic injuries induced by ablative fractional photothermolysis. The forearms of participating volunteers were treated and ablated with a CO2-Laser in a fractional pattern using varying power settings (2.5-10 mJ/MTZ). In vivo RCM and LC-OCT images were obtained at predefined time intervals post-laser treatment, ranging from 6 h to 14 days. Vertical visualization of the lesions through both imaging modalities revealed a healing process characterized by the upward and outward movement of microscopic epidermal necrotic debris, thereby reducing the depth of the injury while forming an external crust. LC-OCT imaging demonstrated more comprehensive results with fewer movement artifacts. Conversely, horizontal visualization with both techniques highlighted a gathering of keratinocytes around the wounds, indicating the initiation of the regenerative process. RCM provided superior image clarity in this horizontal plane. RCM and LC-OCT offer valuable and complementary noninvasive alternatives to conventional biopsy methods for the assessment and characterization of the skin's wound healing process post-ablative fractional photothermolysis. These findings underscore the potential of such imaging techniques in enhancing our understanding of the wound healing process. ClinicalTrials.gov identifier: NCT05614557.

Effect of 3-hydrazinylquinoxaline-2-thiol hydrogel on skin wound healing process in diabetic rats

Impaired wound healing in diabetic individuals creates huge social and financial burdens for both diabetic patients and the health system. Unfortunately, the current treatment has not resulted in consistently lower amputation rates. Quinoxalines are heterocyclic compounds with multiple important pharmacological properties. Their effect on wound healing have not been closely studied. In the current work, the wound healing effect of 3-hydrazinylquinoxaline-2-thiol hydrogel is tested topically in a full-thickness excision wound in streptozotocin-induced type 1 diabetic rats. We examined the wound closure rate, expression of inflammatory factors, growth factors in addition to the histological analysis. The results revealed a significant acceleration in wound closure in the treated group compared with the control experimental animals. Histological data demonstrated enhanced re-epithelialization and collagen disposition. The healing effect was additionally evaluated by the inhibition of the inflammatory response of interleukin (IL)—1β interleukin (IL)—6, tumor necrosis factor (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) with a marked improvement of the transforming growth factor beta (TGFβ-1), antioxidant markers and collagen-1. In silico study indicated a favorable drug-like properties and toxicity profile. The present work showed that 3-hydrazinylquinoxaline-2-thiol holds great potential for the treatment of diabetic wounds.

A multifunctional hydrogel with mild photothermal antibacterial and antioxidant properties based on quercetin and dopamine-coated zinc oxide nanoparticles for healing bacteria-infected wound

Bacterial infection and inflammation hinder the natural healing process of skin wounds and may also cause wound complications. In light of the aforementioned considerations, this study developed an antibacterial and antioxidant QT/PDA@ZnO /QCS/(PAM-PAMPS) hydrogel (QPQH). The hydrogel dressing employs a dual network structure and incorporates quercetin (QT), quaternary ammonium salt chitosan (QCS), and polydopamine-coated zinc oxide nanoparticles (PDA@ZnO NPs) into a Polyacrylamide–Poly(2-acrylamido-2-methyl-1-propanesulfonic acid)（PAM-co-AMPS）hydrogel. This design enables QPQH to exhibit good mechanical properties, remarkable adhesion properties, and the capacity to adhere closely to the wound. The mild photothermal properties (˃50 °C) and Zn2+ release ability of PDA@ZnO NPs can cooperate with the destruction ability of QCS to bacterial cell membranes, thereby achieving efficient sterilization. This process has been demonstrated to be effective against Staphylococcus aureus and Escherichia coli, with approximately 98.5 % and 99.8 % efficiency, respectively. The incorporation of QT into hydrogel confers excellent antioxidant properties, which serve to reduce oxidative stress in wounds and prevent inflammation. Furthermore, hydrogel displays favorable blood compatibility and cell compatibility, facilitating the repair of bacteria-Infected wounds and promoting angiogenesis and collagen deposition in skin wounds. In conclusion, the antibacterial and antioxidant QPQH dressing has considerable potential for clinical use in the treatment of bacteria-Infected wounds.

A simple and universal approach for fabricating bioactive self-stacked hydrogels with enhanced therapeutic efficacy

Despite significant advancements in self-stacked hydrogels of herbal small molecules in recent years, the emergence of new pharmacological small molecule self-stacked hydrogel systems remains largely reliant on serendipity and painstaking efforts. To address this challenge, we proposed a ‘bioactive bivalent metal ions-coordinated pharmacological small molecules’ strategy. This approach enabled the preparation of triterpenoid betulinic acid-based self-stacked hydrogels with excellent injectable and self-healing properties via a simple two-step method. We extended this strategy to self-stacking hydrogels based on other pentacyclic triterpene small molecules, anthraquinone small molecules, flavonoid small molecules and synthetic steroid small molecules. This universal strategy is capable of extracting hydrophobic pharmacological small molecules to construct novel self-stacked biomaterials in a cost-effective, efficient, large-scale, and environmentally friendly manner. Importantly, we successfully synthesized Mg2+-coordinated betulinic acid (BA-Mg) self-stacked hydrogel at low concentrations in the bacterial cellulose (termed BC) hydrogel network, overcoming the mechanical limitations of self-stacked hydrogels for biomedical applications. The BA-Mg/BC hybrid hydrogel demonstrated exceptional biocompatibility, anti-inflammatory, and angiogenic properties, significantly accelerating the skin wound healing process through the synergistic pharmacological effects of Mg2+ and BA.

Photocrosslinked carboxymethylcellulose-based hydrogels: Synthesis, characterization for curcumin delivery and wound healing

Skin could protect our body and regenerate itself to against dysfunctional and disfiguring scars when faced with external injury. As wound dressings, hydrogels are biocompatible, hydrophilic and have a 3D structure similar to the extracellular matrix (ECM). In particular, hydrogels with drug-releasing capabilities are in acute wound healing. In this paper, photocrosslinked hydrogels served as wound dressing based on sodium carboxymethylcellulose (CMC) were prepared to promote wound healing. Photocrosslinked hydrogels were prepared by grafting lysine and allyl glycidyl ether (AGE) onto CMC and encapsulating curcumin (Cur). The synthesized hydrogels had the unique 3D porous structure with a swelling ratio up to 1300 % in aqueous solution. The drug release ratios of the hydrogels were 20.8 % in acid environment, and 14.4 % in alkaline environment. Notably, the hydrogels showed good biocompatibility and antibacterial properties and also exhibited the ability to accelerate the process of skin wound healing while prevent inflammation and scar formation when applied to a mouse skin wound model. As a result, the prepared hydrogels Gel-CLA@Cur showed great potential in wound healing.

Revolutionizing Wound Healing: The Rise of Electrospinning Nanofibers for Bioactive Dressings

A noticeable focus in recent years has been on creating bioactive dressings that are tailored to meet the requirements of wounds that are both acute and chronic. Because of these exceptional properties, electrospinning nanofibers stand out as a potential choice among the creative solutions being investigated. Among these are very high porosity and superior permeability to water and air, both of which are essential for promoting wound healing conditions. Moreover, these nanofibers’ ability to ward against foreign infections makes them an attractive option for improving wound care protocols. It is particularly notable because they closely mimic the extracellular matrix since this property can greatly enhance the efficacy of skin regeneration and wound healing processes. The present study aimed to explore the use of electrospinning nanofibers for bioactive dressings and wound healing. Extensive literature search was performed and relevant articles were collected from various databases like Google scholar, Taylor and Francis, Science direct, Springer, Embase, and Willey. Electrospinning nanofiber applications for the bioactive healing of wounds. The investigation begins with a comprehensive review of the wound healing procedure and the several electrospinning techniques used here. The many natural and synthetic polymers that are used to make electrospinning wound dressings are discussed in more detail. Prominent natural polymers, including hyaluronic acid, collagen, gelatin, silk fibroin, chitosan, and sodium alginate, are emphasized due to their special qualities and possible advantages in wound treatment. Furthermore, the paper explores the wide application of artificial polymers such as polyvinyl alcohol, polyvinyl chloride, polyethylene lactone, polylactide, and polyurethane, providing insight into their roles in the advancement of sophisticated wound dressings. In conclusion, the development of electrospinning technology offers promising prospects for creating improved wound care products and dressings that have the potential to completely transform the wound management industry.

Design Strategy of Microneedle Systems for Skin Wound Healing: Based on the Structure of Tips and Therapeutic Methodologies.

The skin, being the largest organ of the human body, is susceptible to damage resulting in wounds that are vulnerable to pathogenic attacks and fail to provide effective protection for internal tissues. Therefore, it is crucial to expedite wound healing. In recent years, microneedles have garnered significant attention as an innovative drug delivery system owing to their noninvasive and painless administration, simplified application process, precise control over drug release, and versatile loading capabilities. Consequently, they hold immense potential for the treatment of skin wound. This review presents a comprehensive design strategy for the microneedle system in promoting skin wound healing. First, the process of skin wound healing and the characteristics of specific wounds are elucidated. The design strategies for microneedles are subsequently presented and classified based on their structural and therapeutic methodologies. Finally, a succinct recapitulation of the previously discussed points and a prospective analysis are provided.

NF-κB-Signaling-Targeted Immunomodulatory Nanoparticle with Photothermal and Quorum-Sensing Inhibition Effects for Efficient Healing of Biofilm-Infected Wounds.

The development of therapeutics with high antimicrobial activity and immunomodulatory effects is urgently needed for the treatment of infected wounds due to the increasing danger posed by recalcitrant-infected wounds. In this study, we developed light-controlled antibacterial, photothermal, and immunomodulatory biomimetic N/hPDA@M nanoparticles (NPs). This nanoplatform was developed by loading flavonoid naringenin onto hollow mesoporous polydopamine NPs in a π-π-stacked configuration and encasing them with macrophage membranes. First, our N/hPDA@M NPs efficiently neutralized inflammatory factors present within the wound microenvironment by the integration of macrophage membranes. Afterward, the N/hPDA@M NPs effectively dismantled bacterial biofilms through a combination of the photothermal properties of PDA and the quorum sensing inhibitory effects of naringenin. It is worth noting that N/hPDA@M NPs near-infrared-enhanced release of naringenin exhibited specificity toward the NF-κB-signaling pathway, effectively mitigating the inflammatory response. This innovative design not only conferred remarkable antibacterial properties upon the N/hPDA@M NPs but also endowed them with the capacity to modulate inflammatory responses, curbing excessive inflammation and steering macrophage polarization toward the M2 phenotype. As a result, this multifaceted approach significantly contributes to expediting the healing process of infected skin wounds.

Unraveling the Mechanisms Involved in the Beneficial Effects of Magnesium Treatment on Skin Wound Healing.

The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl2, suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl2 treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl2 was inhibited by MMP7 knockdown, suggesting that MgCl2 enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl2 inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial.

A carrier-free injectable hydrogel self-assembled using natural thymol and glycyrrhizin for MRSA-infected wound healing in rats

A carrier-free, self-assembled, injectable hydrogel was developed as wound dressing to deal with skin wound bleeding, bacterial infections, and wound healing. Natural thymol (THY) and glycyrrhizin were used to construct THY-loaded glycymicelles (THY@glycymicelles), which greatly improved the aqueous solubility of THY. Optimal THY@glycymicelles had a high encapsulation efficiency of THY and a uniform nanoparticle size. Interestingly, THY@glycymicelles could reversibly transform into THY@glycyrrhizin hydrogel (THY@glycygel) by adjusting neutral pH to skin pH (pH ∼ 4.9), and vice versa. THY@glycygel had a dense porous sponge microstructure and showed many excellent features, including injectable, hemostatic, antibacterial, and anti-inflammatory properties. In vitro antibacterial evaluation, THY@glycygel showed lower minimum inhibitory concentration to three tested bacteria than free THY. In terms of antibacterial mechanism, THY@glycygel could destroy the bacterial cell wall and membrane, increasing the extracellular alkaline phosphatase release, and inhibiting biofilm. THY@glycygel had strong hemostatic ability and exhibited great potential for antimicrobial activity and improving wound healing infected by methicillin-resistant Staphylococcus aureus (MRSA). Mechanisms including antimicrobial, promoting hair follicle growth, improving epidermis remolding and collagen deposition, decreasing inflammatory cytokine levels, and increasing growth factor levels promoted the MRSA-infected skin wound healing process of THY@glycygel. Totally, this novel hydrogel has great potential as wound dressing.

Application of Hydrogel in Skin Repair

Skin repair has been one of the greatest challenges in human history. Today, with the dramatic increase in chronic diseases and surgical procedures, the demand for wound dressings has gradually increased. Hydrogel, due to their excellent hydrophilicity, biocompatibility and three-dimensional (3D) porous structure, are widely used in wound dressings. In this paper, the process of skin wound healing, the application of hydrogel in skin repair and other applications of hydrogel are introduced. Finally, the development of hydrogel materials in the field of wound healing is prospeced.

Healing of Skin Wounds in Rats Using Creams Based on Symphytum Officinale Extract.

Rosmarinic acid is a well-known natural antioxidant and anti-inflammatory compound, and it is one of the polyphenolic compounds found in comfrey plants. Comfrey root also contains allantoin, which helps with new skin regeneration. This study aimed to investigate the healing and skin regeneration process of skin wounds in Wistar rats using creams based on comfrey extract and to correlate the results with active compounds in the extract. The obtained results showed that comfrey root is rich in bioactive compounds, including allantoin, salvianolic acid, and rosmarinic acid, which are known for their great free radical scavenging activity, and the high antioxidant activity of the extract may be mainly due to these compounds. The obtained extract has an antimicrobial effect on Staphylococcus aureus (1530.76/382.69), Escherichia coli (6123.01/6123.01), and Pseudomonas aeruginosa (6123.01/6123.01). The macroscopic evaluation and the histological analysis of the skin defects 14 days after the intervention showed faster healing and complete healing in the skin excisions treated with oil-in-water cream with 20% extract of comfrey as the active ingredient.

Smart Wound Monitoring and Healing Assessment System With Deep Learning Methods - A Systematic Review

This review describes a Deep Learning Smart Wound Monitoring (DL-SWM) system, focusing on the healing process of both acute and chronic skin wounds. Recognizing the impact of various factors such as environment, patient characteristics, and wound features on the healing timeline, the review emphasizes the need for more efficient wound monitoring methods. The proposed DL-SWM integrates biosensors, a microcontroller, and a fuzzy inference system to assess critical wound indicators, primarily focusing on hydration levels. The hardware design incorporates an Arduino-based biometric sensor device, while the fuzzy inference system predicts the impact of biomarkers on wound hydration. The review study also explores the segmentation of wounds using a Convolutional Neural Network (CNN) called MobileNetV2, providing detailed insights into the wound healing stages. In the literature review, various advancements in wound monitoring technologies, such as hydrogels, clinical decision-making systems, and wearable biological sensors, are discussed. The proposed DL-SWM is compared with existing methods through simulation analysis, demonstrating superior efficiency, accuracy, and lower error rates. The study concludes with the potential prospects of DL-SWM in revolutionizing wound monitoring and treatment, offering a more convenient and effective approach for healthcare practitioners and improving patient outcomes.

Insights into How Plant-Derived Extracts and Compounds Can Help in the Prevention and Treatment of Keloid Disease: Established and Emerging Therapeutic Targets.

Keloid is a disease in which fibroblasts abnormally proliferate and synthesize excessive amounts of extracellular matrix, including collagen and fibronectin, during the healing process of skin wounds, causing larger scars that exceed the boundaries of the original wound. Currently, surgical excision, cryotherapy, radiation, laser treatment, photodynamic therapy, pressure therapy, silicone gel sheeting, and pharmacotherapy are used alone or in combinations to treat this disease, but the outcomes are usually unsatisfactory. The purpose of this review is to examine whether natural products can help treat keloid disease. I introduce well-established therapeutic targets for this disease and various other emerging therapeutic targets that have been proposed based on the phenotypic difference between keloid-derived fibroblasts (KFs) and normal epidermal fibroblasts (NFs). We then present recent studies on the biological effects of various plant-derived extracts and compounds on KFs and NFs. Associated ex vivo, in vivo, and clinical studies are also presented. Finally, we discuss the mechanisms of action of the plant-derived extracts and compounds, the pros and cons, and the future tasks for natural product-based therapy for keloid disease, as compared with existing other therapies. Extracts of Astragalus membranaceus, Salvia miltiorrhiza, Aneilema keisak, Galla Chinensis, Lycium chinense, Physalis angulate, Allium sepa, and Camellia sinensis appear to modulate cell proliferation, migration, and/or extracellular matrix (ECM) production in KFs, supporting their therapeutic potential. Various phenolic compounds, terpenoids, alkaloids, and other plant-derived compounds could modulate different cell signaling pathways associated with the pathogenesis of keloids. For now, many studies are limited to in vitro experiments; additional research and development are needed to proceed to clinical trials. Many emerging therapeutic targets could accelerate the discovery of plant-derived substances for the prevention and treatment of keloid disease. I hope that this review will bridge past, present, and future research on this subject and provide insight into new therapeutic targets and pharmaceuticals, aiming for effective keloid treatment.

α-Catenin promotes dermal fibroblasts proliferation and migration during wound healing via FAK/YAP activation.

Skin wound healing is a complex and organized biological process, and the dermal fibroblasts play a crucial role. α-Catenin is known to be involved in regulating various cellular signals, and its role in wound healing remains unclear. Here, we have identified the pivotal role of the α-catenin/FAK/YAP signaling axis in the proliferation and migration of dermal fibroblasts, which contributes to the process of skin wound healing. Briefly, when α-catenin was knocked down specifically in dermal fibroblasts, the wound healing rate is significantly delayed. Moreover, interfering with α-catenin can impede the proliferation and migration of dermal fibroblasts both invitro and invivo. Mechanistically, the overexpression of α-catenin upregulates the nuclear accumulation of YAP and transcription of downstream target genes, resulting in enhanced the proliferation and migration of dermal fibroblasts. Furthermore, the FAK Tyr397 phosphorylation inhibitor blocked the promoting effects of α-catenin on YAP activation. Importantly, the continuous phosphorylation mutation of FAK Tyr397 reversed the retardatory effects of α-catenin knockdown on wound healing, by increasing the vitality of fibroblasts. Likewise, α-catenin/FAK was validated as a therapeutic target for wound healing in the db/db chronic trauma model. In summary, our findings have revealed a novel mechanism by which α-catenin facilitates the function of fibroblasts through the activity of the FAK/YAP signaling axis. These findings define a promising therapeutic strategy for accelerating the wound healing process.

Magneto-responsive biocomposites in wound healing: from characteristics to functions.

The number of patients with non-healing wounds continuously increases, and has become a prominent societal issue that imposes a heavy burden on both patients and the entire healthcare system. Although traditional dressings play an important role in wound healing, the complexity and diversity of the healing process pose serious challenges in this field. Magneto-responsive biocomposites, with their excellent biocompatibility, remote spatiotemporal controllability, and unique convenience, demonstrate enticing advantages in the field of wound dressings. However, current research on magneto-responsive biocomposites as wound dressings lacks comprehensive and in-depth reviews, which to some extent, restricts the deeper understanding and further development of this field. Based on this, this paper reviews the latest advances in magnetic responsive wound dressings for wound healing. First, we review the process of skin wound healing and parameters for assessing repair progress. Then, we systematically discuss the preparation strategies and unique characteristics of magneto-responsive biocomposites, focusing on magneto-induced orientation, magneto-induced mechanical stimulation, and magnetocaloric effect. Subsequently, this review elaborates the multiple mechanisms of magneto-responsive biocomposites in promoting wound healing, including regulating cell behavior, enhancing electrical signal, controlling drug release, and accelerating tissue reconstruction. Finally, we further propose the development direction and future challenges of magnetic responsive biomaterials as wound dressings in clinical application.