Skin Repair Research Articles

High glucose combined with lipopolysaccharide stimulation inhibits cell proliferation and migration of human HaCaT keratinocytes by impacting redox homeostasis and activating the polyol pathway.

High glucose level and chronic inflammation are characteristic features of diabetic cutaneous wounds. Keratinocytes make up the epidermis and play an important role in skin repair. However, metabolomic changes of keratinocytes in chronic diabetic ulcers have not been fully studied. This study used high levels of glucose combined with lipopolysaccharide to treat human HaCaT keratinocytes. Untargeted metabolomic combined with colorimetric assays were used to explore the changes of keratinocyte metabolites and related metabolic pathways caused by high glucose and lipopolysaccharide. Results demonstrated that high glucose combined with lipopolysaccharide treatment increased intracellular reactive oxygen species and impaired proliferation and migration of keratinocytes. Untargeted metabolomics analysis identified a total of 273 differential metabolites. Redox metabolism associated metabolites were largely altered. Reduced nicotinamide adenine dinucleotide, gamma-glutamylcysteine, superoxide dismutase activity and SOD2 gene expression were significantly upregulated while nicotinamide adenine dinucleotide, glutathione, glutathione peroxidase, several types of lysophosphatidylcholine, lysophosphatidylinositol, and GPR55 gene expression were downregulated. Alterations of glutathione and nicotinamide adenine dinucleotide were verified by colorimetric assays. For the first time, high glucose and LPS were observed to boost the levels of fructose, aldose reductase and sorbitol dehydrogenase of the polyol pathway in HaCaT cells. Further treatment of HaCaT with fructose leading to inhibition of cell proliferation and migration. Our data suggest high glucose combined with lipopolysaccharide significantly altered redox homeostasis associated metabolites and activate the polyol pathway in keratinocytes to impact cell proliferation and migration, providing new strategies for the treatment of chronic diabetic ulcers.

Combined Analysis of Second- and Third-Generation Transcriptome Sequencing for Gene Characteristics and Identification of Key Splicing Variants in Wound Healing of Ganxi Goat Skin

Ganxi goat is a local breed of goat unique to Jiangxi Province, China, named for its primary distribution in the Ganxi region. Ganxi goats are primarily raised through grazing, showing good adaptation to the local humid and hot climate, strong disease resistance, and occupying an important position in the local livestock industry. The skin, as the main barrier of the body, plays an indispensable role in resisting the invasion of external pathogenic factors and has received increasing attention in the medical and scientific fields. In this study, Ganxi goat skin was used as the research subject. Full-length transcriptome sequencing of Ganxi goat skin was performed using PacBio third-generation sequencing technology to supplement and improve the annotation information of the Ganxi goat genome. A combined analysis of second- and third-generation transcriptome sequencing was used to analyze the splicing variant events of hub genes (CDC20, MMP2, TIMP1, and EDN1) and the expression changes in each splicing variant in skin samples on day 0 and day 5 after surgical wounding. The regulatory role of related hub gene splicing variants in wound healing was analyzed. A total of 926,667 full-length non-chimeric sequences were obtained, optimizing the annotation information of 3794 genomic gene loci and identifying 2834 new genes, 256 new LncRNAs, 12,283 alternative splicing events, 549 genes with polyadenylation, and 112 fusion genes. Three splicing variant forms were identified in both the CDC20 and EDN1 genes, seven in MMP2, and two in TIMP1. The expression levels of most splicing variants showed significant changes in the skin samples on days 0 and 5 after wounding, potentially participating in the regulation of wound healing. This study provides fundamental data for the annotation of the goat genome and offers a reference for studying the regulatory mechanisms of wound healing.

Fabrication, Characterization and Release Profile of Aloe Vera Extracts/PVA Composite Electrospun Nanofiber

Aloe vera is a well-known remedy that carries many beneficial health effects such as painkiller, anti-inflammatory, promote skin growth and repair. The combination of bioactive natural product of aloe vera as a drug model and polyvinyl alcohol (PVA) as the base material or carrier in the electrospinning process were studied. Smooth straight and continues electrospun fibers were collected with the Field Effect Scanning Electron Microscope (FESEM) images show no formation of bead (defect signed) in the electrospun membrane when the concentration was set at 10% w/w of PVA nanofibre. The morphological structure of the electrospun membranes shows a smooth and longitudinal fiber when aloe vera is mixed with the PVA polymer with percentage ratio of aloe vera over PVA is less than 25%. The Fourier Transform Infrared Spectroscopy (FTIR) shows no reaction between PVA and aloe vera by not showing peaks other than the initial materials. The Differential Scanning Calorimetry (DSC) proves the presence of aloin indicating the presence of aloe vera in nanofiber. The release profile of the electrospun aloe vera in PVA shows a higher initial burst release at the 50% and 70% concentration levels indicating very little control of the release or none at all. These results show the potential of aloe vera – PVA electrospun nanofibers membrane as a promising material for wound dressing and topical drug delivery.

Utilização de laser de baixa potência como adjuvante no tratamento de ferida por mordedura em um cão

Wounds are structural disorders in the skin that can cause loss of body tissue structure. There are different classifications of wounds, such as open and closed, acute or chronic. Acute wounds heal spontaneously within six weeks, while chronic wounds have delayed healing, which can last more than twelve weeks due to prolonged inflammation. Wound treatment is challenging, especially in animals, due to exposure to dirty places and the owner's lack of awareness. Laser therapy has been used to accelerate wound healing since 1967, promoting pain control, reducing inflammation and modulating the immune system. The skin healing process involves cellular interactions and can be divided into phases, such as inflammatory, proliferative and remodeling. It is believed that laser therapy works by increasing the production of ATP in cellular mitochondria, causing biomodulation and stimulating or inhibiting physiological, biochemical or proliferative activities. Factors such as ray refraction and tissue types influence the penetration of the laser into the tissue, requiring precise positioning to ensure the effectiveness of the treatment. Based on this, the present work aims to contribute to knowledge about laser therapy used for wound healing, presenting the case of a dog with a lacerated wound on thepelvic limb.

Botulinum Toxin Treatment of Psoriasis-A Comprehensive Review.

A literature search on the subject of botulinum toxin treatment in psoriasis found 15 relevant articles, 11 on human subjects and 4 on animal studies. Of the human data, eight were clinical trials and three were single case reports. Seven out of eight clinical trials, all open-label, reported improvement in psoriasis following intradermal or subcutaneous botulinum toxin injections. One double-blind, placebo-controlled study, which used a smaller dose than the open-label studies, did not note a healing effect. Animal studies have shown that injection of botulinum toxins in the skin heals psoriatic skin lesions and can reduce the level of interleukins (ILs) and cytokines as well as inflammatory cells in psoriatic plaques. There is a need for controlled, blinded studies conducted in larger numbers of patients with doses that have shown promise in open-label studies.

Molecular Scarring in Relapsing Psoriasis: Crosstalk of Keratinocytes and Immune Cells

Abstract Introduction/Objective Psoriasis is a chronic skin disorder with a tendency for relapse, characterized by immune- mediated mechanisms leading to papulosquamous lesions. Despite advances in treatment, many patients experience relapse, particularly in previously healed areas, referred to as “molecular scarring.” This scarring suggests a complex interaction between keratinocytes and immune cells, including tissue-resident memory T cells (TRMs), cytokines, and epigenetic modifications, contributing to the pattern-specific recurrence of psoriasis. Methods/Case Report After reviewing 31 articles on PubMed, we focused on the immunopathogenesis of psoriasis, examining the role of TRMs, the balance between regulatory T cells (Tregs) and Th17 cells, and the impact of various treatment modalities on disease recurrence. It evaluates the expression of TRM markers and the effectiveness of treatments such as anti-IL-17 agents and phototherapy in altering disease progression. The study also explores the genomic characteristics of psoriatic lesions post-treatment and the duration of clinical remission associated with different therapeutic approaches. Results (if a Case Study enter NA) The findings demonstrate a significant role of TRMs in psoriasis relapse, with environmental triggers reactivating these cells and leading to the production of inflammatory cytokines. Treatments targeting IL-17 showed a rapid decrease in TRM markers, particularly in the dermis, and were associated with different durations of disease remission based on the therapeutic approach. The study also found that the genomic profile of treated lesions does not fully normalize, with variations in gene expression linked to the type of treatment and possibly influencing the size of the molecular scar and relapse duration. Conclusion Psoriasis relapse is intricately linked to the presence of TRMs and the molecular scarring of previously healed lesions, influenced by various treatment modalities. The study underscores the importance of targeting TRMs and adjusting therapeutic strategies to extend the period of clinical remission and prevent the transition to more severe disease forms. Future research should focus on elucidating the detailed mechanisms of psoriasis relapse and developing targeted treatments to normalize the genomic profile of healed skin, ultimately improving patient outcomes and management of the disease.

Exploring the Role of miR-132 in Rat Bladders and Human Urothelial Cells during Wound Healing

Urinary bladder wound healing shares many features with skin healing, involving several molecular players, including microRNAs (miRs). This study investigated the role of miR-132 in urothelial cells. We analyzed miR-132 expression in rat bladder using in situ hybridization and conducted gain and loss of miR-132 function assays in primary human urothelial cells (HUCs). These assays included cell proliferation and migration studies. To explore the regulation of miR-132 expression, cells were treated with wound-healing-related factors such as interleukin 6 (IL-6), interleukin 10 (IL-10), and transforming growth factor beta-1 (TGF-β1). Predictive bioinformatics and a literature review identified potential miR-132 targets, which were validated through real-time polymerase chain reaction (RT-PCR) and Western blot analysis. miR-132 was found to promote cellular proliferation and migration during the early stages of urothelial wound repair. Its expression was modulated by key cytokines such as IL-6, IL-10, and TGF-β1. miR-132 played a crucial role in urothelial wound healing by enhancing cell proliferation and migration, regulated by cytokines, suggesting its action within a complex regulatory network. These findings highlight the therapeutic potential of targeting miR-132 in bladder injury repair, offering new insights into bladder repair mechanisms.

Epidermal Growth Factor Intralesional Delivery in Chronic Wounds: The Pioneer and Standalone Technique for Reversing Wound Chronicity and Promoting Sustainable Healing.

The early expectations about growth factors' (GFs') discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology was a conundrum at that time. Diabetes undermines keratinocytes' and fibroblasts' physiology, impairing skin healing abilities. Diabetic ulcers, as other chronic wounds, are characterized by hyperinflammation, unbalanced proteolytic activity, catabolism, and free radical cytotoxicity. This hostile scenario for the chemical stability, integrity, and functionality of GFs led to the conclusion that topical administration may jeopardize GFs' clinical effectiveness. Epidermal growth factor (EGF) has a proximal position in tissues homeostasis by activating survival and mitogenic pathways from embryonic life to adulthood. Seminal experiments disclosed unprecedented pharmacological bounties of parenterally administered EGF. Accordingly, the experience accumulated for more than 20 years of EGF intralesional infiltration of diabetic wound bottoms and edges has translated into sustained healing responses, such as low recurrences and amputation rates. This delivery route, in addition to being safe and tolerated, has shown to restore a variety of circulating biochemical markers ordinarily disturbed in diabetic conditions. EGF infiltration triggers a cascade of local fibroblast reactions, supporting its molecular integrity, prolonged mean residence time, and ultimately eliciting its receptor trafficking and nuclear translocation. The intralesional delivery route seems to warrant that EGF reaches wound fibroblasts' epigenetic core, mitigating the consequences of metabolic memory imprinting.

Effectiveness of Azadirachta indica and Ocimum gratissimum for Acne Vulgaris: A Literature Review

Acne vulgaris is a common dermatological condition characterized by inflammation of the pilosebaceous units, predominantly affecting adolescents and young adults. Its multifactorial etiology involves hormonal imbalances, microbial overgrowth, and environmental factors, leading to increased sebum production and inflammation. Conventional treatments often vary in efficacy and tolerability, driving interest in alternative therapies to reduce the severity and recurrence of lesions and enhance appearance, the acne severity. This literature review explores the therapeutic potential of two herbal remedies, Azadirachta indica (Neem) and Ocimum gratissimum (African basil), known for their antimicrobial, anti-inflammatory, and antioxidant properties. Azadirachta indica is recognized for its rich phytochemical profile, including compounds like nimbin and azadirachtin, which effectively combat acne pathogens such as Cutibacterium acnes. Meanwhile, Ocimum gratissimum exhibits significant antimicrobial and antioxidant activities, contributing to skin healing and sebum regulation. The combined use of these herbs offers a holistic approach to acne management, targeting multiple aspects of its pathogenesis, including inflammation and microbial imbalance. The therapeutic benefits of Azadirachta indica and Ocimum gratissimum highlight their valuable role in advancing dermatological care and offer promising prospects for individuals seeking holistic and plant-based solutions for acne management. This review emphasizes the potential and effectiveness of Azadirachta indica and Ocimum gratissimum in advancing dermatological care and providing effective, plant-based solutions for acne management. Keywords: Acne vulgaris, azadirachta indica, clove basil, neem, ocimum gratissimum, treatment

The Effect of Ginkgo Biloba Extract on Oxidative Stress, Anti-Inflammatory and Antiapoptotic in Vitiligo Treated with Topical Desoxymethasone

Vitiligo is a progressive and multifactorial condition of skin, mucosa, and hair depigmentation. Loss of functional melanocytes leads to the appearance of white macules on the skin, often affecting the lips and genitalia. The impact extends to psychological stress, decreased quality of life, and risk of psychiatric morbidity. Various therapeutic strategies have been designed to inhibit the immune response in vitiligo to reduce melanocyte damage while increasing melanocyte repopulation. There is no standardized method of evaluating treatment outcomes in vitiligo patients. Herbal medicines several studies have shown that GB also has many benefits for health and healing skin diseases, one of which is used in treating vitiligo. Therefore, this study aimed to evaluate the potential of Ginkgo biloba extract as a therapeutic supplement in enhancing the positive effects of desoxymethasone on vitiligo. Using a double-blind randomized control trial clinical trial research design, 26 subjects were divided into treatment and control groups. The control group received standard vitiligo therapy with topical desoxymethasone and placebo, while the treatment group received topical desoxymethasone plus Ginkgo biloba extract. Melanin index, VASI score, MDA, TNF-α, CD8 expression, and caspase 3 were measured before and after treatment. The results showed that the administration of Ginkgo biloba extract had a significant effect in reducing MDA, TNF-α, CD8 expression, and caspase 3 levels, and improving melanin index and erythema in vitiligo patients who received topical desoxymethasone therapy. These findings demonstrate the positive potential of Ginkgo biloba extract as an adjunct to vitiligo therapy, resulting in favorable clinical and molecular impacts in patients undergoing combination treatments.

A Young Female’s Battle with Toxic Epidermal Necrolysis Induced by NSAIDs: A Case Report

Introduction: Stevens-Johnson Syndrome (SJS) is a rare but severe mucocutaneous reaction often triggered by medications or infections, characterized by extensive epidermal detachment and mucosal involvement. This condition poses a high risk of morbidity and mortality, requiring prompt recognition and treatment. Case Presentation: An 18-year-old Asian female from eastern Nepal presented with non-itchy red spots, high fever, and significant discomfort following the administration of ibuprofen for minor sores. She developed extensive skin involvement covering 25% of her body surface area and severe mucosal lesions. Laboratory investigations revealed anemia, leukocytosis, and coagulopathy. She was admitted to the ICU, where she received broad-spectrum antibiotics, corticosteroids, and supportive care. The patient also developed acute kidney injury during treatment but eventually recovered and was discharged after a week. Clinical Discussion: The rapid onset of SJS in this patient reveals the unpredictable nature of drug-induced reactions. Early intervention with a multidisciplinary approach involving dermatology, intensive care, and infectious disease specialists was crucial in managing her condition. Despite the controversy surrounding corticosteroid use in SJS, their administration likely contributed to the rapid improvement in inflammation and skin healing. The case highlights the importance of early recognition, prompt management, and careful monitoring for adverse drug reactions, especially when prescribing medications known to cause SJS. Conclusion: The successful outcome achieved through a multidisciplinary approach provides valuable insights into the effective strategies for handling severe drug reactions, emphasizing that early diagnosis and comprehensive management in patients with SJS is critical.

Active Components and Skin Care Mechanism of Sea Grape (Caulerpa lentillifera) Extract

This study successfully obtained sea grape extract through mechanical extraction methods, which is rich in active components. These primary active ingredients include high concentrations of crude polysaccharides, total phenolics, and flavonoids. Using two zebrafish models, we observed significant skin moisturizing and repair effects of this extract. Further experiments demonstrated its remarkable anti-aging and skin tightening effects through the DPPH method and elastase inhibition assay. Additionally, the extract showed significant anti-inflammatory effects in a model built on 3 dpf (days post fertilization) Tg (corola: EGFP) transgenic zebrafish. The extract’s safety and reliability were confirmed through a final dermal application test on rabbits. Furthermore, we also analyzed the possible mechanism of Caulerpa lentillifera extract skin care. Overall, our research indicates that sea grapes hold tremendous potential as a novel natural ingredient for skincare. It is foreseeable that sea grapes will become an indispensable component in the future medical skincare market.

Sticky Science: Using Complex Coacervate Adhesives for Biomedical Applications.

Tissue adhesives are used for various medical applications, including wound closure, bleeding control, and bone healing. Currently available options often show weak adhesion or cause adverse effects. Recently, there has been an increasing interest in complex coacervates as medical adhesives. Complex coacervates are formed by mixing oppositely charged macromolecules that associate and undergo liquid-liquid phase separation, in which the dense bottom phase is the complex coacervate. Complex coacervates are strong and often biocompatible, and show strong underwater adhesion. The properties of the resulting materials are tunable by intrinsic factors such as polymer chemistry, molecular weight, charge density, and topology of the macromolecules, as well as extrinsic factors such as temperature, pH, and salt concentration. Therefore, complex coacervates are interesting new candidates for medical adhesives. In this review, it is described how complex coacervates form and how different factors influence their behavior. Next, an overview of recent studies on complex coacervates in the context of medical adhesives is presented. The application of complex coacervates as hemostatic or embolic agents, skin or bone repair adhesives, and soft tissue sealants is discussed. Lastly, additional possibilities for utilizing these materials in the future are discussed.

Epidemiology of complications after non-compulsory planned hardware-removal after limbs fracture

IntroductionRemoval of hardware (HR) following a fracture is a frequent question from patients. The incidence of this kind of intervention remains very variable depending on the healthcare systems and its interest is debated in view of the benefits and associated risks that remain poorly defined. Mandatory preoperative information cannot be given optimally in this context. ObjectiveTo determine the rate of complications (major and minor) after non-compulsory planned hardware-removal following a limb fracture. HypothesisThe rate of major complications was greater than 1%. MethodsA 10-year retrospective single-center study included 1990 patients who had undergone routine HR. Analysis of medical records, with a minimum of one year of follow-up, allowed us to collect: patient data, the type and anatomical location of the osteosynthesis material, as well as the occurrence of a postoperative complication, categorized as a major complication (resulting in either a new surgical procedure, re-hospitalization, or lasting functional impairment) or a minor complication. ResultsOverall, 4.1% (79/1990) of patients experienced postoperative complications, including 1.56% (31/1990) major complications and 21 surgical revisions (1.06%). The time to onset of complications was 9.1 +/- 8.4 days. The most common complications were deep infections and impaired skin healing with superficial infection (55/79, 69.6%). Locations "around the knee" and "around the ankle" were at higher risk of complications (p < 0.01). Smoking was identified as a significant risk factor for complications, particularly deep infection (p = 0.004, OR = 8.7 [1.98; 38.11]). DiscussionNon-mandatory routine RH has a significant complication rate even in a healthy population. Preoperative information of the patient and the assessment of the benefit/risk balance are essential in this indication. This study also raises the question of mandatory smoking cessation preoperatively. Level of evidenceIV; retrospective study.

Simvastatin and adenosine-co-loaded nanostructured lipid carriers for wound healing: Development, characterization and cell-based investigation

Chronic wounds represent a significant global health burden, characterized by delayed skin healing and associated comorbidities. The present study aimed to develop nanostructured lipid carriers (NLCs) as a topical delivery system for the co-administration of simvastatin and adenosine to address chronic wound management. The rationale behind the co-delivery approach was to mitigate the cytotoxicity associated with high-dose simvastatin, while preserving its therapeutic benefits through a potential synergistic or additive effect. A significant challenge in the development of these NLCs was the encapsulation of the highly hydrophilic adenosine within the hydrophobic lipid matrix. The NLCs were prepared using a hot homogenization-sonication method with a double emulsion technique and optimized through a series of formulation trials, employing various surfactants, solid and liquid lipids, to achieve efficient drug encapsulation, particularly for the hydrophilic adenosine. Optimized formulations F5- and F10-S/A 0.6 %/2 % (containing 0.6 % simvastatin and 2 % adenosine), exhibited promising physicochemical properties. The main difference was the liquid lipid used: F5 containing Miglyol 810 N, while F10 Capmul MCM C-8. Both formulations displayed a mean particle size below 230 nm, a polydispersity index (PDI) of approximately 0.2, and a zeta potential of around –22 mV. While simvastatin association efficiency (AE) was nearly 100 %, adenosine AE was higher for F10 (24 %), compared to F5 (13.5 %). F5 demonstrated superior stability compared to F10, maintaining consistent particle size and PDI over a 60-day period. Formulation F5 also demonstrated superior cell-based in vitro performance compared to F10, with higher cell viability (MTT assay), greater cell proliferation induction (SRB assay), and enhanced cell proliferation and migration in the wound-scratch assay. While F10 displayed higher adenosine AE, F5 excelled in terms of stability and biological activity. The slightly increase in intracellular reactive oxygen species levels observed with F5 may contribute to its enhanced proliferative effects. In-depth characterization revealed that F5 comprised spherical nanoparticles, and thermal analysis indicated no significant changes in the nanocarrier structure upon drug encapsulation. Additionally, ex vivo permeability study demonstrated superior skin retention of both simvastatin and adenosine for F5 compared to an emulsion control. Overall, the F5 nanocarrier demonstrated suitable physicochemical properties, cellular biocompatibility, induction of cell proliferation and migration events, and drug retention capacity in the skin layers, indicating its potential as a promising topical treatment for difficult-to-heal wounds.

Periostin regulates the activity of keloid fibroblasts by activating the JAK/STAT signaling pathway

A keloid is secondary to skin trauma or has spontaneously manifested as an overgrowth and occurs when the skin heals abnormally after an injury. The main pathological manifestations are abnormal proliferation of keloid fibroblasts (KEL-FIB). This study researched periostin (POSTN) on keloid fibroblasts (KEL-FIB) and the associated mechanism, aiming to provide a reference for the targeted therapy of keloid. We got tissues from Second People’s Hospital of Guangxi Zhuang Autonomous Region between June 2022 and March 2023. POSTN expression was increased in keloid skin tissue and KEL-FIB than normal skin tissue and normal fibroblasts. We collected and inoculated KEL-FIB cells, transfection of si-NC (Silencing of POSTN negative control), si-POSTN (Silencing of POSTN), pcDNA-NC (Overexpression of POSTN negative control), and POSTN (Overexpression of POSTN) (Thermo Fisher Scientific) used Lipofectamine 2000 transfection reagent. Wound closure, cell proliferation viability, migrated cell numbers, and POSTN, p-JAK2, p-STAT3 protein levels were reduced in the si-POSTN group. Wound closure, cell proliferation viability, migrated cell numbers, and POSTN, p-JAK2, p-STAT3 protein levels were elevated in the POSTN group. POSTN protein levels did not changed and wound closure, cell proliferation viability, migrated cell numbers, were reduced in the POSTN+S-Ruxolitinib group. The study results indicated that POSTN promotes cell migration and proliferation by activating the JAK/STAT pathway, promoting KEL-FIB development.

Homology-based identification and structural analysis of Pangasius hypophthalmus Annexins and Serine proteases to search molecules for wound healing applications

Chronic wounds and burns are a worldwide healthcare problem that erodes patients’ well-being and healthcare systems. This silent and costly epidemic requires new, cost-efficient solutions to improve patients’ physical and economic welfare. Eschar-degrading vegetal and bacterial proteases have been utilized as a solution. However, these proteins are evolutionarily far from those present in human wound healing. Serine protease (SP) and annexin (ANX) proteins interact within the skin healing process. A homology-based identification pipeline can help in discovering selective human SP and ANX analogs in the epithelial tissue of the fast-healing species, Pangasius hypophthalmus. In the present work, we found 14 candidates for RT-PCR in P. hypophthalmus using homology inference. The genetically detected candidates were then structurally and sequentially analyzed to understand their possible relation to SPs and ANXs involved in human wound healing. A total of six TBLASTN/BLASTX candidates (four SPs and two ANXs) were detected in P. hypophthalmus skin. Structural analysis revealed that all SP candidates resembled human KLK4, KLK5, KLK6, and KLK8, whereas all ANX only resembled human ANXA4. Structure and sequence analysis revealed high conservation of ANX Ca2+ binding sites (GDXD) and SP catalytic triad (HDS) motifs. In addition, structural analysis revealed that SP substrate selectivity position 186 was the main difference between human KLK5 and P. hypophthalmus SPs. These findings may allow the proposal and testing of more selective formulations, broadening treatments beyond debridement.

Spatial Dimension Cues Derived From Fibrous Scaffolds Trigger Mechanical Activation to Potentiate the Paracrine and Regenerative Functions of MSCs via the FAK-PI3K/AKT Axis

Secretomes from mesenchymal stem cells (MSCs) have significant therapeutic potential and could be the basis for future MSCs treatments. Innovative design of the topology of biomaterials, which mechanically regulate cell behavior and function, can tremendously improve the efficacy of stem cell therapy. However, how spatial dimension cues derived from specific topology command cell mechanotransduction to regulate the paracrine function of MSCs remains unknown. In this study, the three-dimensional (3D) fibrous constructs with box-like pores and precise strand spacing from 150 μm down to only 40 μm were manufactured using melt electrowriting (MEW), which were used to systematically investigate the spatial dimension cues-triggered mechanotransduction of adipose-derived mesenchymal stem cells (Ad-MSCs) and their impact on the paracrine and regeneration function of Ad-MSCs. The results demonstrated that spatial instructions from the 3D fibrous constructs could influence the spatial reorganization of the cytoskeleton, resulting in cell elongation and augmented immunomodulatory and angiogenic paracrine effects of Ad-MSCs, which was most pronounced at a minimum strand spacing of 40 μm. Besides, mechanical activation of the FAK-PI3K/AKT axis significantly enhanced the paracrine function of Ad-MSCs. In vivo experiments demonstrated that the Ad-MSCs trained using well-defined 3D fibrous constructs with a strand spacing of 40 μm significantly promoted skin regeneration via paracrine signals. In conclusion, this study provides a new horizon for deciphering space dimension insights into the interactional mechanisms of mechanotransduction in regulating cell function, which has inspired innovations in biomaterials for improving tissue regeneration. Statement of SignificanceDesigning cell-scale spatial dimension cues in engineered constructs potentiates the paracrine and regenerative functions of Ad-MSCs.FAK-PI3K/AKT signaling serves as the key mechanotransduction checkpoints for spatial dimension cues triggering mechanical activation.Paracrine signals of Ad-MSCs triggered by mechanical activation promotes skin repair and regeneration via the immunomodulation and angiogenesis.

Diabetic Microenvironment‐Unlocked BioHJzyme with H2S Evolution for Robust Anti‐Pathogens and Hyperinflammatory Wound Regeneration Through TGF‐β/Smad Pathway

AbstractDeferred diabetic skin healing is an ever‐growing complication owing to the hyperglycemic microenvironment, which accelerates the generation of advanced glycated end products (AGEs) and provides a hotbed for pathogenic infection. Here, the H2S‐evolving bio‐heterojunction enzyme (BioHJzyme), which is consisted by MXene/FeS2 and glucose oxidase (GOx) is devised. It presents glutathione peroxidase (GPx)‐ and peroxidase (POD)‐mimetic antibacterial activity for anti‐pathogens and wound regeneration by AGEs depression. The GOx catalyzes glucose, resulting in reducing the bacterial nutrient and supplying H2O2. The POD‐mimetic activity of the BioHJzyme catalyzes the H2O2 to hydroxyl radical (•OH) with a turnover number of 4.45 × 10−1 s−1, while the GPx‐mimetic activity of it consumes glutathione for further •OH accumulation. The anti‐pathogens can be enhanced by near infrared laser (NIR) irradiation owing to the efficient separation of electron‐hole pairs originated from the heterostructure, which presents NIR‐activatable •OH and 1O2 production. Moreover, the BioHJzyme evolves H2S in acidic environment, acting as an H2S donor, which protects cells around the wound from oxidative damage and AGEs, rescues mitochondrial respiration, improves the extracellular matrix deposition and ameliorates dysfunction of fibroblasts for diabetic skin regeneration through TGF‐β/Smad pathway. The work provides a proof‐of‐concept for bacteria‐invaded diabetic wound regeneration via H2S‐evolving BioHJzyme.

Fabrication of thymol-loaded isabgol/Konjac glucomannan-based microporous scaffolds with enriched antioxidant and antibacterial properties for skin tissue engineering applications.

An antioxidant, antibacterial, and biocompatible biomaterial is essential to repair skin wounds effectively. Here, we have employed two natural biopolymers, isabgol (ISAB) and konjac glucomannan (KGM), to prepare microporous scaffolds by freezing and lyophilization. The scaffolds are loaded with thymol (THY) to impart potent antioxidant and antibacterial activities. The physicochemical properties of the ISAB + KGM + THY scaffold, like porosity (41.8 ± 2.4%), swelling, and biodegradation, were optimal for tissue regeneration application. Compared to the control, ISAB + KGM + THY scaffolds promote attachment, migration, and proliferation of L929 fibroblasts. The antioxidant activity of the ISAB + KGM + THY scaffold was significantly improved after loading THY. This would protect the tissues from oxidative damage. The antibacterial activity of the ISAB + KGM + THY scaffold was significantly higher than that of the control, which would help prevent bacterial infection. The vascularization ability of the ISAB + KGM scaffold was not altered by incorporating THY in the ISAB + KGM scaffold. Therefore, a strong antioxidant, antibacterial, and biocompatible nature of the ISAB + KGM + THY scaffold could be useful for various biomedical applications.