Toward Intelligent and Personalized Skin Healing: Responsive Natural Hydrogels Bridging Sensing and Therapy.

Curcumin, a pleiotropic polyphenol derived from Curcuma longa, has gained considerable interest as a potential adjuvant therapy in dermatology due to its anti-inflammatory, antioxidant, antimicrobial and immunomodulatory properties. Preclinical studies demonstrate that curcumin modulates key molecular pathways involved in skin disease, including NF-κB, JAK–STAT, MAPK and Nrf2 signalling, affecting keratinocytes, fibroblasts, melanocytes, sebocytes and cutaneous immune cells. These findings have led to an increasing number of clinical studies investigating oral and topical curcumin, novel formulations and photodynamic applications across various dermatological conditions, such as psoriasis, atopic dermatitis, acne, pigmentary disorders, chronic wounds and photoaging. Clinical evidence suggests potential benefit as an adjunct to standard therapy in psoriasis, inflammatory and pruritic dermatoses, limited vitiligo and selected wound-healing settings, while data for cosmetic and infectious indications remain preliminary. Overall, curcumin shows a favourable safety profile, with mostly mild gastrointestinal or local adverse effects, though emerging reports of hepatotoxicity and drug interactions warrant caution with high-dose or long-term systemic use. Its clinical translation is limited by poor bioavailability, heterogeneous formulations, small and methodologically weak trials and lack of outcome standardisation. This narrative review summarises current mechanistic and clinical evidence, highlights limitations and identifies priorities for future research to better define curcumin’s role in modern dermatology.

Chronic wounds have been a significant clinical challenge, owing to their persistent inflammation, poor regeneration, and high infection risk. This necessitates advanced strategies for real-time monitoring and effective treatment, and natural polymer-based hydrogels, composed of renewable materials such as polysaccharides, proteins, and plant-based macromolecules, serve as compelling candidates for engineering multifunctional smart dressing. This review summarizes recent advances in natural polymer-based smart hydrogels with a primary focus on their applications in wound monitoring and stimuli-responsive therapy. Following a brief overview of chronic wound pathophysiology and the fundamental design principles of natural polymer hydrogels, the integration of sensing mechanisms for real-time monitoring of critical wound biomarkers (e.g., pH, enzymes, temperature, reactive oxygen species (ROS)) is summarized. Particular emphasis is placed on integrated platforms that combine sensing and treatment capabilities. The review also discusses the integration of hydrogels with wearable electronics and closed-loop feedback mechanisms in advanced hybrid systems. Finally, the remaining challenges and future perspectives regarding the development of multimodal, artificial intelligence (AI)-assisted precision wound management technologies are outlined.

Advancements in hydrogels: A comprehensive review of natural, synthetic, and hybrid innovations for wound healing.

Disorders of skin barriers: clinical implications.

Recent advances in natural macromolecule-based hydrogels for treating oral soft tissue inflammation: A review.

A compact pulse-modulation air plasma jet for the inactivation of chronic wound bacteria: Bactericidal effects & host safety

Bleach baths for atopic dermatitis: Evidence of efficacy but more data are needed

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

Diabetes is a condition correlated with a high number of diagnosed chronic wounds as a result of a complex pathophysiological mechanism. Diabetic chronic wounds are characterized by disorganized and longer stages, compared to normal wound healing. Natural polymer hydrogels can act as good wound dressings due to their versatile physicochemical properties, represented mainly by high water content and good biocompatibility. Natural bioactive hydrogels are polymers loaded with bioactive compounds providing antibacterial and antioxidant properties, modulation of inflammation and adherence to wounded tissue, compared to traditional dressings, which enables promising future applications for diabetic wound healing. Natural bioactive compounds, such as polyphenols, polysaccharides and proteins have great advantages in promoting chronic wound healing in diabetes due to their antioxidant, anti-inflammatory, antimicrobial, anti-allergic and wound healing properties. The present paper aims to review the wound healing mechanisms underlining the main issues of chronic wounds and those specifically occurring in diabetes. Also, the review highlights the recent state of the art related to the effect of hydrogels enriched with natural bioactive compounds developed as biocompatible functional materials for improving diabetic-related chronic wound healing and providing novel therapeutic strategies that could prevent limb amputation and increase the quality of life in diabetic patients.

Constitutive KIT Activity and IL-6 Production in Mast Cells Alters Levels of Reactive Oxygen Species (ROS) and the Scavenger Protein DJ-1 in Mastocytosis

BackgroundDrug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation of reactive oxygen species (ROS). An effective solution would be to not only combat bacterial infections but also scavenge ROS to relieve inflammation at the wound site. Scaffolds with antioxidant properties are attractive for their ability to scavenge ROS, and there is medical demand in developing antioxidant enzyme-mimicking nanomaterials for wound healing.MethodsIn this study, we fabricated copper-coordination polymer nanoparticles (Cu-CPNs) through a self-assembly process. Furthermore, ε-polylysine (EPL), an antibacterial and cationic polymer, was integrated into the Cu-CPNs structure through a simple one-pot self-assembly process without sacrificing the glutathione peroxidase (GPx) and superoxide dismutase (SOD)-mimicking activity of Cu-CPNs.ResultsThe resulting Cu-CPNs exhibit excellent antioxidant propertiesin mimicking the activity of glutathione peroxidase and superoxide dismutase and allowing them to effectively scavenge harmful ROS produced in wound sites. The in vitro experiments showed that the resulting Cu-CPNs@EPL complex have superior antioxidant properties and antibacterial effects. Bacterial metabolic analysis revealed that the complex mainly affects the cell membrane integrity and nucleic acid synthesis that leads to bacterial death.ConclusionsThe Cu-CPNs@EPL complex has impressive antioxidant properties and antibacterial effects, making it a promising solution for treating drug-resistant bacterial infections in chronic wounds. The complex’s ability to neutralize multiple ROS and reduce ROS-induced inflammation can help relieve inflammation at the wound site.Graphical Schematic illustration of the ROS scavenging and bacteriostatic function induced by Cu-CPNs@EPL nanozyme in the treatment of MRSA-infected wounds.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by impaired skin barrier function and immune dysregulation. Despite advancements in understanding its pathogenesis, clinical management remains challenging due to high recurrence rates, complex symptom control, and diminished quality of life, particularly highlighting the lack of standardized protocols for skin barrier repair. Compromised skin barrier integrity in AD leads to increased transepidermal water loss (TEWL) and heightened susceptibility to irritants and allergens, exacerbating inflammation. Thus, restoring skin barrier function is pivotal in AD management. Current therapeutic strategies predominantly prioritize anti-inflammatory treatments while undervaluing barrier repair. Traditional care models relying on qualitative symptom assessments inadequately guide personalized interventions, necessitating an integrated approach combining barrier restoration and immunomodulation. Although diverse barrier repair methods and moisturizers are available, systematic evaluation and evidence-based selection criteria remain limited. This review aims to comprehensively summarize the structure and function of the skin barrier in AD, the role of skin barrier dysfunction in AD pathogenesis, current barrier repair strategies, and evidence-based emollient selection criteria. By analyzing existing research, we provide clinical recommendations for skin barrier restoration and long-term management in AD patients, while proposing future research directions. Emphasis should be placed on developing multi-omics-driven personalized barrier interventions and constructing a “barrier-immune-environment” interaction model to advance precision medicine in AD care.

Until recently, atopic dermatitis (AD) has been linked to Th1/Th2 cell dysregulation. But now, the opinion that inflammation in AD results from a convergence of inherited and acquired insults to the cutaneous permeability barrier, with variable contributions from inherited abnormalities in innate/adaptive immunity, is becoming increasingly accepted. Current therapy is however, still largely directed towards ameliorating immunologically triggered inflammation, rather than correcting the barrier abnormality. In this article, the authors provide an overview of epidermal barrier function; a review of recent molecular genetic studies pointing to a primary barrier abnormality in AD; a detailed description of new pathogenic insights into AD; and they compare the efficacy of several putative 'barrier repair' products currently utilized as adjunctive or primary therapy for AD. The authors also explore the potential of 'next-generation' barrier repair approaches that attack specific pathogenic mechanisms in AD (high surface pH, elevated serine protease activity, activation of the PAR2 receptor and Staphylococcus aureus secondary infections).

Many recent studies have revealed the key roles played by Th1/Th2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the pathogenesis of atopic dermatitis. Accordingly, current therapy has been largely directed towards ameliorating Th2-mediated inflammation and/or pruritus. We will review here emerging evidence that the inflammation in atopic dermatitis results from inherited and acquired insults to the barrier and the therapeutic implications of this new paradigm. Recent molecular genetic studies have shown a strong association between mutations in FILAGGRIN and atopic dermatitis, particularly in Northern Europeans. But additional acquired stressors to the barrier are required to initiate inflammation. Sustained hapten access through a defective barrier stimulates a Th1 --> Th2 shift in immunophenotype, which in turn further aggravates the barrier. Secondary Staphylococcus aureus colonization not only amplifies inflammation but also further stresses the barrier in atopic dermatitis. These results suggest a new 'outside-to-inside, back to outside' paradigm for the pathogenesis of atopic dermatitis. This new concept is providing impetus for the development of new categories of 'barrier repair' therapy.

The management of complex dermatological disorders, including chronic inflammatory diseases, non-healing wounds, and skin malignancies, often faces significant challenges. These include limited efficacy against chronic or relapsing conditions, the emergence of drug-resistant pathogens, and significant side effects from long-term therapies. This clinical gap highlights the urgent need for novel therapeutic agents. Resveratrol (RES), a natural polyphenol with pleiotropic bioactivities, has emerged as a compelling candidate substantiated by its diverse modulatory effects on cutaneous pathophysiology. This review aims to critically synthesize the evidence for RES’s efficacy, dissect its foundational mechanisms, and explore innovations in drug delivery designed to overcome its clinical limitations. This review critically synthesizes evidence of the efficacy of RES in managing challenging dermatological conditions, including chronic wounds, psoriasis, atopic dermatitis, melanoma, acne, and herpes simplex virus infections, by dissecting its foundational antioxidant, anti-inflammatory, and immunomodulatory mechanisms. Its therapeutic action is mediated through critical molecular pathways, notably the activation of SIRT1/AMPK and suppression of NF-κB, which collectively mitigate oxidative stress, normalize cellular proliferation, and recalibrate immune responses. Although systemic bioavailability limitations have historically hindered RES’s clinical translation, innovative delivery systems, including nanoparticles, hydrogels, and advanced transdermal formulations, are now revolutionizing its topical application and markedly enhancing its localized efficacy and stability. This review consolidates robust preclinical evidence from animal models demonstrating RES-driven accelerated wound healing, diminished inflammatory markers, and significant tumor suppression while also appraising nascent yet promising clinical trial data that indicate good tolerability and initial efficacy in human subjects. Ultimately, this synthesis crystallizes RES as a versatile and promising therapeutic agent in dermatology, concurrently underscoring the imperative for continued innovation in delivery methodologies and execution of large-scale stringently designed clinical trials to fully unlock its therapeutic potential.