Search Results (656)

Chronic diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, oxidative stress, and defective tissue remodeling, leading to delayed healing. Cordyceps militaris, a medicinal fungus with known anti-inflammatory and antioxidant properties, has shown therapeutic potential in metabolic disorders; however, its role in diabetic wound repair remains unclear. In this study, we evaluated the wound-healing effects of an aqueous extract of C. militaris using in vitro keratinocyte models and a streptozotocin-induced diabetic mouse model. C. militaris treatment significantly accelerated wound closure, improved epidermal regeneration, and enhanced skin barrier integrity. Mechanistically, C. militaris restored HIF-1α and TGF-β1 expression, promoted cell proliferation and fibroblast activation, and increased the expression of matrix metalloproteinases MMP-1 and MMP-2, indicating enhanced extracellular matrix remodeling. In parallel, excessive inflammatory responses were attenuated, as evidenced by reduced IL-6 and TNF-α levels, along with activation of SIRT1/Nrf2/HO-1 antioxidant signaling pathways. Collectively, these findings demonstrate that C. militaris promotes a balanced wound-healing microenvironment and represents a promising natural therapeutic candidate for the treatment of diabetic wounds. Full article

Cosmeceutical peptides (CPs), which modulate various biological activities, including skin regeneration and wound healing, have emerged as promising agents in skincare. In this study, we investigated the regenerative and wound healing potential of a short peptide, CP-02 (sequence CDARSDAR), using human dermal fibroblast cells (HDFs) in vitro and a zebrafish model in vivo. In HDFs, CP-02 treatment at concentrations of 50, 100, and 200 µg/mL significantly accelerated wound closure in a dose-dependent manner (p < 0.05) and upregulated the mRNA expression of CCND1, MYC, FGF2, EFG, and IL-8 at 12 h post-treatment. In amputated zebrafish larvae, exposure to CP-02 (5 µg/mL) for 72 h significantly increased fin regeneration, with a fin area of 3.5 mm² and fin-fold length of 0.2 mm, compared with those in controls (2 mm² and 0.07 mm, respectively). Intramuscular administration of CP-02 significantly improved the healing rates in wounded adult zebrafish to 58% and 76% on 12 and 16 days post wounding (dpw), respectively, compared with the vehicle (35% and 44%, respectively). Histological analysis (H&E staining) revealed reduced inflammatory cell infiltration, complete granulation, and re-epithelialization in the CP-02-treated tissues at 12 dpw. Furthermore, mRNA expression levels of tnf-α, il-1β, tgfb1, mmp9, mmp13, and timp2b were elevated in the CP-02 group at 4 dpw, whereas those of pro-fibrotic mediators, including acta2, ctgfb, cdh1, and col9a3 reduced in muscle tissue on 12 dpw. Collectively these findings demonstrate that CP-02 promotes effective, scar-reducing regeneration and wound healing, highlighting its strong potential as a therapeutic peptide for future skincare and cosmeceutical applications. Full article

Hydrogels are three-dimensional hydrophilic network structures with one or more polymers cross-linked, with excellent biocompatibility, drug-carrying function, and biodegradability. Meanwhile, skin wound repair includes hemostasis and coagulation, an inflammation stage, a proliferation stage, and a remodeling stage. Therefore, hydrogels loaded with natural products are widely used in repairing skin wounds through various mechanisms such as hemostasis, antibacterial activity, anti-inflammatory activity, angiogenesis promotion, skin regeneration, and skin repair monitoring. In addition, this study provides the cross-linking mechanism (physical cross-linking and chemical cross-linking) and construction mode (self-assembly and physical parcels) of the loaded natural product hydrogel. In general, the purpose of this paper is to comprehensively understand the mechanism and preparation strategy of hydrogels loaded with natural products for skin repair and provide theoretical reference for future skin repair research. Full article

Disorders of skin wound healing and the repair of full-thickness skin defects remain significant clinical challenges. Natural polysaccharide-based hydrogels, with their excellent biocompatibility, tunable degradability, and multifunctional properties (e.g., antibacterial, antioxidant, and pro-angiogenic), have emerged as key materials for designing wound dressings and skin tissue engineering scaffolds. This review systematically summarizes recent advances in polysaccharide hydrogels—including chitosan, hyaluronic acid, and alginate—focusing on material types, crosslinking strategies, and functional modifications, with particular emphasis on their dual applications in wound healing (acute and chronic wounds) and skin tissue engineering. In wound healing, these hydrogels regulate the microenvironment through multiple mechanisms, including anti-inflammatory, antioxidant, pro-angiogenic, and immunomodulatory effects. In skin tissue engineering, their three-dimensional porous structures mimic the extracellular matrix, supporting cell adhesion, proliferation, and tissue regeneration. Finally, we discuss the challenges and future prospects for the clinical translation and commercialization of natural polysaccharide hydrogels. Full article

This paper proposes a potential solution to the current issue of developing advanced, biocompatible biomaterials with integrated therapeutic functionality, which would contribute to improving the treatment of skin defects. This study aimed to develop, characterize and evaluate hydrogels based on type I collagen, pectin, alginate and myrtle essential oil, in order to obtain biomaterials with potential in skin regeneration applications. Hydrogels incorporating alginate, pectin, type I collagen and Myrtus communis essential oil were prepared via a multistep procedure comprising homogenization, crosslinking and lyophilization. The obtained hydrogels were characterized by physicochemical and structural methods, such as FTIR spectroscopy, to identify interactions between components; micro-computed tomography, to evaluate internal morphology and porosity; antibacterial tests, for evaluating the ability of the hydrogel to prevent infections at the application site; and in vitro cellular tests, such as the XTT test or cytotoxicity tests, such as LDH, essential for evaluating the biocompatibility of the hydrogel. The highest viability value was recorded for sample J4 (99.53 ± 11.88%), indicating an exceptional compatibility with the cells used, almost identical to that of the untreated control. The samples showed encouraging results, supporting their potential for applications in wound treatment and skin regeneration. Full article

Current wound-healing strategies still fall short in achieving scarless regeneration. Adult wounds often heal in the form of scars, leading to functional impairment and aesthetic concerns. In contrast, fetal wounds exhibit a remarkable capacity for scarless regeneration due to their unique immune environment and regenerative cellular responses. This review systematically elucidates the key mechanisms underlying scarring and contrasts them with the hallmarks of fetal scarless healing. We then comprehensively explore engineering strategies to minimize scar formation in adults, with a focus on the combined application of regenerative biomaterials, bioactive factors, and cell therapies. Particularly emphasis is placed on novel intelligent biomaterials for reprogramming wound immune microenvironment and precise delivery strategies of “spatiotemporal sequential” or “on-demand”. These innovations signify a shift toward precise and controlled therapeutic intervention, offering new pathways for skin regeneration that enhances both functionality and aesthetics. Full article

Background: Wounds with an avascular component represent a significant challenge in medical care due to impaired blood flow. Synthetic matrices, such as poly-lactic acid (PLA), have demonstrated promising results in promoting wound healing in complex wounds, including those with restricted blood supply, such as diabetic foot and venous leg ulcers. Objective: This case series presents the outcomes of five patients with wounds containing exposure of avascular components, of various etiologies successfully treated with PLA matrices. Case description: Five patients presented complex wounds involving exposure of bone, tendon, fascia, or osteosynthetic material. Wound bed preparation included debridement followed by PLA application covered with additional layers (non-adherent dressing, absorbent dressing, and compression bandage) as needed. Weekly assessments were conducted until full wound closure was achieved. Results: All cases showed successful outcomes, with PLA promoting granulation tissue formation and re-epithelialization, contributing to wound closure. One patient required skin grafts for complete healing. No local infections were reported before or after PLA application. Conclusions: PLA matrices are a practical and effective option for managing complex wounds, promoting tissue regeneration and optimizing wound bed quality for skin grafts or flaps. While these findings are promising, further studies are needed to confirm the broader applicability and efficacy of PLA in the management of wounds containing exposure of avascular structures. Full article

Background/Objectives: Wound healing requires simultaneous pain control, inflammation management, infection prevention, and tissue regeneration. This study aimed to develop and evaluate in vitro a non-contact thermosensitive spray hydrogel combining lidocaine for rapid analgesia and allantoin for tissue repair. Methods: The effects of chitosan and Poloxamer 407 on viscosity, spray diameter, and bioadhesion ability of hydrogels were optimized using response surface methodology. Lead formulations (S1 and S2) were selected via a desirability function within the software. The pH, gelation temperature (T_G), rheological behavior, sprayability, bioadhesion, and lidocaine release using the dialysis bag method were assessed. The in vitro cytotoxicity, anti-inflammatory activity (TNF-α), and cell migration (scratch assay) of the formulations were investigated. Results: The viscosity values (42.7–58.7 mPa·s) indicated suitability for spraying at room temperature. T_G was 28.7 ± 0.6 °C (S1) and 29.3 ± 0.3 °C (S2), enabling rapid sol–gel transition at skin temperature. The lidocaine release reached 95–100% within 120 min. S2 exhibited lower viscosity and wider spray diameter, improving applicability on larger wound areas. In vitro cytotoxicity, scratch assay, and inflammatory marker analyses demonstrated that the optimized sprayable hydrogels exhibited a biocompatible and cell-healing profile. Conclusions: The developed thermosensitive spray hydrogel enables the combined delivery of lidocaine and allantoin, rapid gelation at body temperature, and touch-free administration. Its suitable viscosity and sprayability, and fast lidocaine release profile indicate high patient compliance and a significant advantage over conventional cream/ointment formulations, particularly regarding painless application, reduced contamination risk, enhanced therapeutic potential, and confirmed in vitro biocompatibility with supportive effects on keratinocyte behavior. Full article

Background/Objectives: Sulfated hyaluronic acid (sHA) is a chemically modified derivative of native hyaluronic acid (HA), characterized by enhanced physicochemical stability and increased biological activity. Glycosaminoglycans (GAGs), including HA, are key regulators of skin structure, hydration, and immune homeostasis. This review aims to critically summarize current knowledge on the structural and functional properties of GAGs—particularly HA and its sulfated forms—and to explore their potential dermatological applications in skin aging and inflammatory diseases such as atopic dermatitis, psoriasis, and acne. Methods: A narrative literature review was conducted using PubMed and Scopus databases up to June 2025, including experimental, preclinical, and clinical studies investigating the biological effects, mechanisms of action, and dermatological uses of sHA compared with native HA and other HA derivatives. Results: Compared with HA, sHA demonstrates increased enzymatic resistance, higher charge density, and improved water-binding and antioxidant capacity. These properties contribute to the restoration of skin barrier function, modulation of oxidative stress and inflammation, and promotion of extracellular matrix remodeling. Preclinical evidence supports the efficacy of sHA in reducing dryness, irritation, and inflammatory responses in atopic dermatitis, psoriasis, and acne. Preliminary findings also suggest potential benefits in wound healing and skin barrier repair. Conclusions: sHA represents a promising multifunctional molecule in dermatology and cosmetology, capable of reducing inflammation and supporting tissue regeneration. However, current evidence remains limited to preliminary studies. Future controlled clinical trials are required to confirm efficacy, optimize formulations, and establish standardized treatment protocols. Full article

The Olea europaea L., commonly known as the European olive, has been recognized for centuries as one of the most valuable species among useful plants. In contemporary applications, the olive tree provides a wide array of raw materials utilized in the food, pharmaceutical, and nutraceutical industries. Extracts derived from the leaves, bark, and fruits of O. europaea have also gained significant relevance in dermatological and cosmetic formulations. The aim of this paper was to review scientific studies published between 2019 and 2025 concerning the application of olive oil and other derivatives of the European olive in the care of skin, hair, and nails. The analysis underscores the role of olive-derived bioactives in wound healing, stretch mark management, and skin regeneration, highlighting compounds such as oleocanthal and oleuropein in hydration, elasticity, wrinkle reduction, and photoprotection relevant to skin aging. The evidence for olive oil in hair and nail care mainly highlights their moisturizing and strengthening effects, though studies remain limited. O. europaea derivatives show a favorable safety profile with low allergenic potential, and their availability and minimal sensitization risk support use in home cosmetics. The importance of the European olive and its products is expected to grow in the coming years. However, the availability of technologies for processing waste materials obtained from this plant, as well as the associated technological costs, remain significant limitations. Full article

Background/Objectives: Diabetic foot ulcers (DFUs) are one of the most debilitating complications of diabetes mellitus, characterized by impaired wound healing, chronic inflammation, and neuropathy. Peripheral nerve degeneration plays a critical role in delayed healing, but the molecular mediators linking hyperglycemia, neurodegeneration, and impaired DFU repair remain incompletely understood. This study aims to characterize the expression of activin A, which is a key regulator of fibroblast activity and neuronal growth, tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), which mediates inflammatory and apoptotic signaling, and synaptophysin, which serves as a marker of axonal sprouting and synaptic remodeling in diabetic tissues. Methods: Skin tissues during wounding and after healing from control and diabetic Sprague–Dawley rats were analyzed using histological staining, immunohistochemistry, and quantitative real-time polymerase chain reactions. Additionally, rat fibroblasts were treated with hyperglycemic medium to evaluate gene and protein expression in vitro. Results: Histological analyses revealed impaired healing in diabetic wounds with reduced collagen deposition, loss of adnexal structures, and disorganized tissue architecture. Gene and protein expression of activin A, TNFRSF10B, and synaptophysin were significantly decreased in diabetic healed tissues compared to controls. In vitro, hyperglycemia induced transient upregulation of activin A and TNFRSF10B at 24 h, followed by a decline at 48 and 72 h. Conclusions: These findings indicate that hyperglycemia disrupts key mediators of axonal regeneration in DFUs, potentially contributing to impaired neuronal regeneration and delayed healing. Targeting these molecular pathways may offer therapeutic opportunities to enhance wound repair in DFUs. Full article

Background: Diabetic foot ulcers (DFUs) are chronic wounds with high morbidity and mortality. Secretory proteins coordinate intercellular communication and may regulate inflammation, tissue repair and regeneration, but their contributions to DFU pathogenesis remain unclear. Aim: To discover and validate secretory protein–linked biomarkers that distinguish non-healing DFUs and to explore their potential utility for diagnosis and therapy. Methods: We integrated bulk RNA-sequencing datasets (GSE199939 training set; GSE80178 and GSE143735 validation sets) and a single-cell RNA-sequencing dataset (GSE223964). Differentially expressed genes, secretory protein lists, and weighted gene co-expression networks were intersected to select candidates. Functional enrichment, protein interaction networks and support vector machine–recursive feature elimination identified key markers. We visualized their cell-type distribution at single-cell resolution and validated their expression in external cohorts. Pathway enrichment, gene co-expression networks, ceRNA regulatory analysis and qRT-PCR in patient samples were used for further characterization. Results: Among 4803 differentially expressed genes, 743 overlapped with known secretory proteins. WGCNA highlighted modules strongly associated with DFUs, yielding 386 candidates. SVM-RFE combined with protein interaction analysis pinpointed four secretory proteins—LYZ, MPO, SLCO2B1 and TREM2—as putative biomarkers. Single-cell analyses showed that MPO, LYZ, SLCO2B1 and TREM2 transcripts are detectable in multiple skin-resident and immune cell populations, and that the DFU-associated upregulation of MPO and LYZ is most pronounced within keratinocyte clusters, while MPO and TREM2 remained consistently dysregulated in independent bulk cohorts. MPO-associated genes were enriched for immune and inflammatory pathways, whereas TREM2-linked genes implicated cell cycle and cytoskeletal regulation. GeneMANIA and ceRNA analyses revealed extensive interaction networks. qRT-PCR confirmed differential expression of MPO and TREM2 in clinical DFU tissues. Conclusions: Integrated multi-modal analysis identifies secretory proteins, particularly MPO and TREM2, as central determinants of impaired healing in DFUs. These molecules and their regulatory networks represent promising biomarkers and therapeutic targets for precision management of diabetic wounds. Full article

Wound healing is a complicated process that involves hemostasis, antibacterial defense, and tissue regeneration. Conventional treatment methods, such as surgical suturing, have inherent limitations, necessitating the exploration of new ones. Hydrogels can create a moist environment that facilitates wound healing, making them an ideal material for wound healing. In this study, a procoagulant polysaccharide mixture (carboxymethyl chitosan/sodium alginate/fucoidan; CAF) was designed. Hydrogels were prepared using CAF and an oxidized starch/tannic acid blend (OT) at different ratios. Through comprehensive evaluations, such as gelation time, swelling capacity, and antibacterial efficacy, an optimal hydrogel (COT) was identified. This COT hydrogel was formed by mixing 3% CAF and OT solutions at a ratio of 2:1 (v/v). The associated gelation process occurred rapidly within 13 s. COT hydrogel exhibited self-healing properties, and a high swelling rate (~3109 ± 74%). It also demonstrated high antibacterial activity, facilitating enhanced protection against infection. Additionally, COT hydrogel exhibited biocompatibility and biosafety. COT hydrogel demonstrated low cytotoxicity on mice fibroblast cells (L929) and good hemocompatibility in vitro. Moreover, in vivo evaluations revealed that it did not cause skin irritation or allergic reactions. Importantly, COT hydrogel significantly outperformed the commercially available hydrogel with its hemostatic and wound healing performance (p < 0.001, p < 0.01). Full article

This study investigates electrospinning methodologies using distilled water as an environmentally friendly and non-toxic solvent for fabricating nanofibers composed of fish collagen (COL) and pullulan (PUL). The underlying hypothesis is that incorporating PUL will enhance the spinnability of the electrospun solution through the formation of hydrogen bonds with COL, thereby facilitating improved fiber development within an aqueous system. This study examined the interactions between COL and PUL molecules, focusing on hydrogen bonding and the consequential alterations in secondary structural conformation, to elucidate their effects on the spinnability and stability of COL in water-based solutions. Furthermore, this study emphasizes the advantages of needle-free electrospinning, which enables the efficient production of nanofibers and offers scalability potential for industrial applications. The architecture and properties of the resultant ultra-thin COL/PUL fibers were comprehensively characterized, underscoring their suitability for various biomedical applications. The development of PUL-based skin nanofibers represents a significant advancement in the field of biomaterials, offering a biocompatible and biodegradable alternative for dermatological applications, including skin regeneration, wound healing, drug delivery, tissue engineering, and cosmetic science. The benefits of needle-free electrospinning, such as enhanced production efficiency and scalability, are particularly emphasized, demonstrating its potential for the large-scale commercial manufacturing of biocompatible nanofibers. This study aimed to address the research gap regarding the use of distilled water as an eco-friendly and safe solvent for electrospinning nanofibers made from collagen and pullulan. This study aimed to investigate the unexplored potential of distilled water for this application. Full article

Wounds are disruptions of the dermal layer of the skin caused by physical, chemical, thermal, infectious, or immunological insults. Given the skin’s critical role in maintaining homeostasis and protecting against external threats, prompt and effective wound healing is essential to restore functionality and prevent further complications. Numerous natural products (NPs) have long been employed in wound care due to their antioxidant, anti-inflammatory, antimicrobial, and regenerative properties. Building on this historical and scientific foundation, the present literature review consolidates and critically evaluates recent experimental and clinical evidence on the wound healing potential of marigold (Calendula officinalis L.). By focusing on studies published between 2020 and 2025, this review captures the evolving understanding of the plant’s therapeutic applications, particularly in skin regeneration and wound management. For each selected publication, formulation type, intervention strategy, dosage, and key outcomes (such as healing rate, cell proliferation, and modulation of inflammatory markers) were summarized. This synthesis aims to provide an update on current evaluations involving C. officinalis and how this plant contributes to dermal repair and to identify promising directions for future research and clinical applications. Full article