Search Results (1,429)

Plant-derived extracellular vesicles (PDEVs), also referred to as plant exosomes or exosome-like nanovesicles, have emerged as promising natural bioactive nanoparticles for cosmetic and regenerative applications. Owing to their biocompatibility, intrinsic bioactive cargo, and ability to interact with mammalian cells, PDEVs are increasingly investigated as agents for skin rejuvenation, wound healing, photoprotection, pigmentation control, and skin barrier enhancement. However, the available evidence remains fragmented across different plant sources and experimental models. This review aimed to summarize and critically evaluate the current evidence regarding the cosmetic and regenerative properties of PDEVs. Experimental studies investigating the effects of PDEVs on skin cells, reconstructed skin models, animals, or human subjects were systematically identified and analyzed. The available evidence consistently demonstrated that PDEVs promote skin regeneration and tissue repair. The most frequently reported effects included enhanced keratinocyte and fibroblast proliferation and migration, accelerated wound closure, increased collagen synthesis, reduced oxidative stress, activation of antioxidant defense pathways, and suppression of inflammatory responses. Additional studies reported improvements in skin barrier function, hydration, photoprotection, pigmentation control, and cellular senescence. Collectively, the available studies demonstrate consistent regenerative, antioxidant, anti-inflammatory, and skin-protective effects of PDEVs. Overall, PDEVs represent multifunctional bioactive nanomaterials with substantial potential for cosmetic applications. While clinical translation remains limited by regulatory and standardization challenges, cosmetic use appears to offer a more immediate route toward commercialization. Further standardization, mechanistic studies, and clinical investigations are required to support the broader implementation of PDEV-based technologies. Full article

Background: Diabetes accelerates atherosclerosis and restenosis and impairs vascular healing, complicating percutaneous coronary intervention (PCI). Drug-coated balloons (DCBs) deliver antiproliferative therapy without a permanent scaffold, but their comparative mid-term performance in diabetic patients relative to non-diabetic patients is incompletely defined. Methods: We analysed a large all-comers cohort of consecutive patients who underwent a DCB-based PCI between 2018 and 2022, stratified by diabetes status. The primary endpoint was a composite of cardiac death, target vessel revascularisation (TVR) and target vessel myocardial infarction. Cumulative incidence was estimated by Kaplan–Meier analysis, and predictors were assessed by Cox regression. Results: Among 853 patients (304 diabetic, 549 non-diabetic), diabetic patients had more comorbidities and more frequent in-stent restenosis (52.3% vs. 41.8%). Over a median follow-up of 376 days, the two-year incidence of the composite endpoint was higher among diabetic patients (21.3% vs. 10.6%, p = 0.007), as was target lesion revascularisation (TLR; 13.6% vs. 5.5%, p = 0.004). Diabetes independently predicted the composite endpoint (adjusted hazard ratio: 1.87; 95% CI: 1.10–3.17) and TLR (adjusted HR: 2.33; 95% CI: 1.18–4.62), whereas DCB type and procedural variables did not. Conclusions: In an all-comers DCB-PCI population, diabetes was independently associated with higher rates of mid-term major adverse cardiovascular events and target lesion revascularisation, while device and procedural variables did not drive outcomes, underscoring the importance of systemic risk management in regard to diabetic patients. Full article

Neuroblastoma is an aggressive pediatric malignancy with limited therapeutic options for high-risk disease, underscoring the need for alternative treatment strategies. Drug repurposing offers a promising approach to accelerate the identification of effective anti-cancer agents. In this study, we investigated the anti-carcinogenic effects of hydroquinidine, a class IA antiarrhythmic ion channel blocker, and spiramide, a dopamine D₂/serotonin 5-HT₂ receptor antagonist and endoplasmic reticulum stress inducer, in SH-SY5Y human neuroblastoma cells. Cells were treated with increasing concentrations of each compound and evaluated using cell viability, colony formation, wound healing, proliferation, apoptosis, and quantitative gene expression assays. Both compounds induced a dose-dependent reduction in cell viability, with spiramide exhibiting greater potency than hydroquinidine. Functional assays revealed significant suppression of clonogenic survival, cell migration, and DNA synthesis, accompanied by increased oxidative stress and cell death. Molecular analyses demonstrated coordinated transcriptional regulation of apoptosis- and cell cycle-related genes, characterized by upregulation of BAX, CDKN1A, and CDKN1B, and downregulation of BCL-2 and CCND1. Notably, spiramide consistently produced stronger cytotoxic and wound-closure inhibitory effects, suggesting a greater contribution of oxidative stress- and apoptosis-associated pathways. Collectively, these findings indicate that hydroquinidine and spiramide disrupt neuroblastoma cell growth through complementary stress- and cell cycle-associated pathways and identify them as promising candidates for further preclinical evaluation. Full article

Background/Objectives: A hydrogel with enhanced therapeutic properties was developed using chitosan, dextran sulfate, and Aloe vera-coated nanoparticles encapsulating eucalyptus extract. Methods: The physicochemical characteristics of the synthesized nanoparticles were evaluated using transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and antibacterial activity assays. The in vitro release profile of Eucalyptus staigeriana extract was assessed at physiological pH 7.4, and the in vivo wound healing performance was subsequently investigated in a rat model. Results: The results indicated that the nanocarrier system provided a controlled and sustained release of eucalyptus extract. Aloe vera-coated dextran sulfate/chitosan nanoparticles encapsulating E. staigeriana inhibited the growth of Staphylococcus aureus by 40%. Moreover, animals treated with Aloe vera @ DX/CS/EE nanoparticles exhibited markedly improved wound contraction, with mean reductions of 27.45%, 19.18%, 18.12%, and 7.03% compared with the control, DX/CS nanoparticles, Aloe vera @ DX/CS nanoparticles, and DX/CS/EE nanoparticles groups, respectively. Histological analysis further confirmed that treatment with Aloe vera @ DX/CS/EE nanoparticles led to superior tissue organization and accelerated dermal regeneration. Conclusions: Overall, the dextran sulfate/chitosan hydrogel coated with Aloe vera and loaded with eucalyptus extract demonstrates strong potential as an effective wound dressing material capable of enhancing healing outcomes. Full article

Background: Platelet concentrates are widely used in regenerative dentistry and maxillofacial surgery; however, the lack of protocol standardization and selection criteria results in contradictory clinical outcomes. This study aimed to perform a comparative analysis of the biological activity of various platelet concentrates obtained via different fractionation and activation procedures under uniform in vitro experimental conditions. Methods: Rat adipose-derived stem cells (ADSCs) and human EA.hy926 endothelial cells were used to evaluate four platelet concentrate types via tube formation, wound healing (scratch), and cell proliferation assays. Results: Platelet concentrates obtained by the single-centrifugation protocol (L-PRP-1) exhibited maximal retained platelet potential, corresponding to a peak 5-fold increase in cell migration. Chemical activation of plasma-based concentrates (L-PRP, P-PRP) with calcium/thrombin was critically required to trigger angiogenesis and accelerate endothelial chemotaxis. Conversely, plasma-free platelet concentrate (PFPC) exhibited a unique capacity for spontaneous activation and clot formation without exogenous inducers, triggering rapid angiogenesis and sustaining ADSC proliferation. Conclusions: Within the framework of our in vitro model, activated plasma-based forms are biologically justified for accelerated soft tissue healing and socket preservation, whereas the complete removal of plasma proteins suggests the potential utility of PFPC as a biomimetic matrix-carrier for maxillofacial tissue engineering. Full article

The skin serves as the largest protective barrier organ of the human body and is easily impaired by trauma, infection and chronic diseases. Efficient wound dressings are indispensable for repairing infected wounds. Isochlorogenic acid A (IAA), the core active ingredient of Shanyinhua, has superior anti-inflammatory and antibacterial effects. However, low water solubility and weak structural stability restrict its direct application in wound treatment. In this work, IAA@Fe(III) nanoparticles (IAA@Fe(III) NPs) were synthesized through self-assembly and loaded into cross-linked amylopectin (Amy)/carboxymethyl chitosan (CMCS) (AC hydrogel) to construct Amy/CMCS@NPs composite dressings. Characterizations demonstrated that nanoparticles displayed a uniform spherical shape with a size of 114.20 ± 2.29 nm and stable coordination. The hydrogel featured a dense porous structure and outstanding mechanical performance, self-healing ability, adhesion, and swelling properties. In vitro tests proved that 50 mg/mL composite hydrogel exerted nearly 100% bacteriostatic activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with good biocompatibility, and enhanced cell migration capacity. In vivo assays indicated an 86.5% wound healing rate at day 7. This dressing could downregulate Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β), upregulate Cluster of Differentiation 31 (CD31) and Vascular Endothelial Growth Factor (VEGF), and accelerate wound repair. This study provides a theoretical and experimental basis for the exploitation of IAA-based wound dressings and high-value utilization of Shanyinhua resources. Full article

The escalating prevalence of bacterial infections has intensified the search for innovative antimicrobial strategies, particularly for infected wound management. Chondroitin sulfate (CS), a naturally occurring glycosaminoglycan with established biocompatibility, presents an attractive scaffold for developing metal ion-functionalized biomaterials. This study reports the fabrication of chondroitin sulfate–copper complex (CSCu) and chondroitin sulfate–zinc complex (CSZn) through an ion exchange method, wherein Cu²⁺ and Zn²⁺ ions bind to the groups of carboxylate, sulfate, or N-acetyl from the CS backbone. The resulting complexes exhibited copper or zinc loading capacities of about 6.6% and demonstrated potent antibacterial activity against E. coli and S. aureus. The integration of CSCu or CSZn with sodium alginate yielded a hydrogel system with a higher apparent viscosity, possessing injectability and spreadability on the skin surface and a porous three-dimensional internal structure conducive to wound healing applications. In a murine model of S. aureus-infected full-thickness wounds, topical application of CSCu and CSZn hydrogels substantially accelerated wound closure, achieving 97.46% and 98.11% healing, respectively, by day 10. Additionally, treatment with CSCu or CSZn hydrogels significantly attenuated systemic inflammatory responses, as reflected in lowered serum TNF-α, IL-1β, and IL-6 alongside increased IL-10. Histological evaluation confirmed enhanced re-epithelialization and stratum spinosum formation in treated wounds. These findings establish CSCu and CSZn as a promising bioactive agent for addressing bacterial wound infections through a dual mechanism of direct antibacterial action and immunomodulatory effects, offering a valuable alternative to conventional antibiotic therapies. Full article

Background: Platelet-rich plasma (PRP) plays a crucial role in chronic wound healing by releasing growth factors that regulate inflammation, promote angiogenesis, and stimulate tissue regeneration. Methods and Results: Here, an animal source of PRP, named ApiRegenin and derived from cultivated deer blood, was established. Specific protein and non-protein biomarkers—including nicotinamide, palmitic acid, IGF, and fibronectin—were validated to ensure batch-to-batch quality control. The pharmacological properties of ApiRegenin in cultured cells transfected with DNA encoding HRE and NF-κB reporter constructs were validated, serving as a functional control. In a skin-defective model of db/db diabetic mice, accelerated wound healing was observed following ApiRegenin treatment. Histological analysis revealed enhancements of re-epithelialization, granulation tissue formation, and collagen deposition. In parallel, the immunofluorescence staining of CD31, α-SMA, and VEGF was upregulated, indicating the promotion of angiogenesis. Furthermore, ApiRegenin treatment shifted the local immune microenvironment toward an M2-like macrophage phenotype, characterized by the downregulation of iNOS and the contrastive upregulation of Arg-1. At the molecular level, transcriptomic enrichment analysis suggested the prominent involvement of the HIF-1, PI3K-Akt, and TNF signaling pathways. Conclusions: These findings demonstrate that ApiRegenin effectively accelerates diabetic wound healing by promoting angiogenesis and modulating macrophage polarization. Full article

Impaired wound healing is often caused by persistent inflammation, bacterial infection, and insufficient extracellular matrix remodeling. Natural polymer-based hydrogels represent ideal wound dressings but often struggle to balance structural stability and biological activity. Herein, we report a dual-functional network regulation strategy enabled by highly soluble mussel foot protein (HMFP) that acts simultaneously as a structural crosslinking regulator and bioactive effector to fabricate synergistic hydrogels (CS-SH-H) from β-chitosan (CS) and sodium hyaluronate (SH). HMFP homogenizes the porous microstructure, strengthens intermolecular interactions, and significantly improves thermal and structural stability via multivalent non-covalent bonding. In vitro, CS-SH-H shows excellent cytocompatibility, significantly promotes fibroblast proliferation and migration, and exerts potent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In a mouse full-thickness skin defect model, the hydrogel dramatically accelerates wound closure, reducing the residual wound area to 25% on day 7, outperforming the control groups. Immunohistochemistry confirms that HMFP suppresses TNF-α-mediated inflammation and enhances Ki-67-positive cell proliferation, leading to accelerated re-epithelialization and collagen deposition. This study establishes HMFP as a promising marine-derived dual-functional network regulator for designing high-performance hydrogel dressings. This strategy is scalable and translatable for treating infected and inflammatory wounds. Full article

Background: Effective management of bone defects remains a major clinical challenge, driving continuous efforts to develop bioactive, localized delivery systems that support bone regeneration. Gold nanoparticles (AuNPs) have gained attention in regenerative medicine for their capacity to modulate cellular activity. Yet, their application in functional delivery systems for bone repair is still limited. Chitosan (CS), a naturally derived biopolymer, exhibits notable osteoinductive properties, particularly when used to modify nanoparticulate carriers. Objectives: In this study, AuNPs and chitosan-coated gold nanoparticles (CS-AuNPs) were formulated, characterized, and incorporated into gel preparations to evaluate their physicochemical properties and therapeutic potential in a rat tibial bone defect model. Methods: AuNPs were synthesized and either left uncoated or coated with CS to enhance biological activity. Both formulations were examined for particle size, zeta potential, X-ray diffraction, and Fourier-transform infrared spectroscopy (FTIR). The resulting nanoparticles were integrated into gel bases, which were assessed for gel strength, swelling index, viscosity, and pH. The in vivo study involved surgically induced bone defects in the tibias of albino rats treated with either formulation. Healing outcomes were assessed via histological analysis, quantification of newly formed bone, immunohistochemical staining, radiographic imaging, and measurement of bone-related markers using RT-qPCR. Results: The CS-AuNP gel formulation demonstrated significantly improved bone regeneration compared to the uncoated counterpart, as evidenced by histological findings, increased bone volume in radiographs, stronger immunohistochemical expression of the VEGF angiogenic protein marker, and increased genetic expression of osteogenic markers. Conclusions: Incorporating CS-AuNPs into gel formulations offers a promising approach for enhancing bone healing. The superior performance of the CS-coated system highlights its potential as a promising localized therapy for managing bone defects. Full article

Diabetic oral mucosal wounds exhibit impaired healing and require biomaterials with strong wet adhesion, favorable biocompatibility, and adequate mechanical stability. In this study, an in situ photocurable adhesive hydrogel (ATDS) based on sulfonated chitosan was developed for diabetic oral mucosal wound repair. ATDS exhibited a tensile strength of 50 kPa, an elongation at break of 320%, and an adhesive strength of 0.605 MPa, while also displaying a porous microstructure without obvious cytotoxicity. Compared with hyaluronic acid (HA) gel, which was completely lost by day 3, ATDS provided more durable wound coverage in the oral environment. In a diabetic rat model of oral mucosal defect, ATDS significantly accelerated wound closure, with wounds nearly completely healed by day 6, promoted re-epithelialization as early as day 3, and increased epidermis thickness by approximately 50% compared with the control group. In addition, ATDS enhanced angiogenesis and reduced the expression of the inflammatory cytokines TNF-α and IL-1β. Collectively, these findings demonstrate that ATDS effectively promotes diabetic oral mucosal wound healing through its barrier-protective, pro-angiogenic, and anti-inflammatory effects, highlighting its potential as a promising biomaterial for oral tissue engineering and regenerative applications. Full article

Oral ulcerations are complex pathological lesions with multifactorial etiology and diverse clinical manifestations. Current treatment options are mostly symptomatic with a different adverse effect. Therefore, this study aimed to develop a mucoadhesive oral gel containing Potentilla erecta L. ethanol extract (PEOG) and evaluate its healing effects in a rat model of oral ulceration. Dried rhizomes of Potentilla erecta were extracted with 70% ethanol using ultrasonic extraction, followed by low-pressure evaporation. The extract was incorporated into a gel base composed of poloxamer 407 and carbomer 934. Rheological characterization was performed to assess the viscoelastic and flow properties of the formulation. Therapeutic efficacy was evaluated through macroscopic assessment of ulcer healing, histopathological analysis, and determination of systemic oxidative stress biomarkers. Animals were assigned to three groups: untreated control, gel base (GB), and PEOG-treated. Rats were sacrificed on days 0, 3, 6, and 10 for blood and tissue sampling. PEOG treatment significantly accelerated ulcer healing, resulting in a marked reduction in ulcer size compared with controls. Histopathological findings indicated enhanced collagen deposition, while biochemical analyses suggested attenuation of oxidative stress. These results demonstrate that PEOG possesses considerable ulcer-healing potential and may represent a promising mucoadhesive formulation for the treatment of oral ulcerations. Full article

To address the challenges associated with prolonged inflammatory phases and delayed healing in clinically infected wounds, this research developed a multifunctional PB@GC@OD hydrogel integrating self-healing properties, injectability, and photothermal antibacterial efficacy. The hydrogel was constructed using oxidized dextran (OD) and glycol chitosan (GC) as the matrix, which were dynamically cross-linked via a Schiff-base reaction to form the GC@OD hydrogel. Subsequently, the photothermal agent prussian blue (PB) was incorporated to fabricate the PB@GC@OD hydrogel. The resulting PB@GC@OD hydrogel demonstrated robust self-healing capabilities and excellent injectability. Upon exposure to 808 nm near-infrared (NIR) irradiation, the hydrogel achieved efficient photothermal conversion, rapidly inducing localized hyperthermia that effectively eliminated Staphylococcus aureus, Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA). In a mouse model of MRSA-infected wounds, the hydrogel not only maintained a moist wound microenvironment but also eradicated pathogenic bacteria via photothermal therapy, thereby significantly accelerating the healing process. Moreover, the hydrogel demonstrated favorable biocompatibility and long-term safety. Therefore, the PB@GC@OD hydrogel integrates photothermal sterilization, self-healing, injectability, hemostasis, and biocompatibility into a single platform, presenting a promising strategy for synergistic therapy and tissue regeneration in bacterially infected wounds. Full article

Background/Objectives: Burn injuries in children represent a significant clinical challenge, as current standard-of-care agents such as silver sulfadiazine (SSD) present limitations, including delayed re-epithelialization. This study aimed to evaluate the therapeutic potential of Castanea sativa (sweet chestnut) flower extract—rich in polyphenols and flavonoids with documented antioxidant, anti-inflammatory, and antimicrobial properties but previously uncharacterized in burn wound healing—applied topically on second-degree burn wounds in a juvenile rat model, comparing its efficacy to SSD and their combination. Methods: Forty five-week-old female Wistar albino juvenile rats were randomly allocated into five groups (n = 8): burn control (Group C), SSD monotherapy (Group BS), vaseline vehicle/sham (Group Sham), 5% chestnut flower extract (Group BCs), and SSD combined with extract (Group BSCs). All topical treatments were applied once daily for 14 days. Healing outcomes were assessed by macroscopic wound closure analysis, systemic organ stress markers (ALT, AST, BUN), oxidative stress indices (MDA, SOD, CAT, GPx, GSH), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10), and histopathological/immunohistochemical analyses (Ki-67, VEGF). Results: All active treatment groups demonstrated significant reductions in organ damage markers, oxidative stress burden, and pro-inflammatory cytokine levels, alongside enhanced antioxidant enzyme activity, compared to Group C (p < 0.001). Extract-treated groups exhibited more pronounced suppression of oxidative and inflammatory parameters than SSD monotherapy. The combination group (BSCs) achieved optimal wound healing outcomes, including near-complete re-epithelialization, superior collagen organization, and prominent angiogenesis, corroborated by the highest Ki-67 proliferation index and VEGF expression scores (p < 0.001). Conclusions:C. sativa flower extract significantly accelerates burn wound healing via antioxidant and anti-inflammatory mechanisms. When combined with SSD, a synergistic effect is observed that overcomes the re-epithelialization delays associated with SSD monotherapy. These findings support C. sativa flower extract as a promising candidate for further preclinical and clinical investigation in pediatric burn management, supporting the ethnopharmacological relevance of this plant in traditional wound care practices; further safety and efficacy validation is required before clinical translation. Full article

Persistent inflammatory and metabolic stress contribute to impaired tissue repair, particularly under diabetic conditions. Agave potatorum is traditionally used in Mexico to treat inflammation and wounds; however, its safety profile and potential to modulate stress-associated biological responses remain poorly investigated. This study evaluated the safety, anti-inflammatory, and wound-healing activities of the hydroalcoholic extract of A. potatorum and its fractions. Safety was assessed using human keratinocytes and fibroblasts, as well as an acute oral toxicity assay (OECD Guideline 420) in female CD-1 mice. Anti-inflammatory activity was evaluated using a TPA-induced ear edema model, while wound-healing activity was assessed in normoglycemic and alloxan-induced diabetic male CD-1 mice. The hydroalcoholic extract exhibited a favorable safety profile, showing low cytotoxicity at therapeutically relevant concentrations and no signs of systemic toxicity at 2000 mg/kg. The hydroalcoholic extract and its EtOAc and n-BuOH fractions significantly reduced TPA-induced ear edema. The n-BuOH fraction also accelerated wound contraction in diabetic mice from day 6 onward, whereas only limited effects were observed in normoglycemic animals. A. potatorum exhibits a favorable preclinical safety profile and modulates biological responses associated with inflammatory stress, supporting its therapeutic potential for chronic diabetic wound healing. Full article