Search Results (1,658)

Background/Objectives: Phages show efficacy against multidrug-resistant Pseudomonas aeruginosa, but limited host ranges require combining them in cocktails. In this work, we characterized 25 P. aeruginosa phages, developed therapeutic cocktails active against diverse clinical isolates, and tested phage efficacy in a mouse incisional wound model. Methods/Results: These phages represent seven genera, and genomic and phenotypic analyses indicate that 24/25 are lytic and suitable for phage therapy. Phage host ranges on a diversity panel of 156 P. aeruginosa strains that included 106 sequence types varied from 8% to 54%, and together the 24 lytic phages were active against 133 strains (85%). All of the phages reduced bacterial counts in biofilms. A cocktail of five lytic phages, WRAIR_PAM1, covered 56% of the strain panel, protected 100% of mice from lethal systemic infection (vs. 20% survival in the saline-treated group), and accelerated healing of infected wounds. An improved five-phage cocktail, WRAIR_PAM2, was formulated by a rational design approach (using phages with broader host ranges, more complementing activity, relatively low resistance background, and compatibility in mixes). Conclusions: WRAIR_PAM2 covered 76% of highly diverse clinical isolates and demonstrated significant efficacy against topical and systemic P. aeruginosa infection, indicating that it is a promising therapeutic candidate. Full article

Ocular allergy (OA) is a subtype of seasonal allergy that causes symptoms of itchiness, redness, swelling and irritation of the ocular surface and eyelids, often triggering allergy-induced eye rubbing and sustained inflammation for up to six months of the year during peak allergy season. These symptoms, coupled with reduced sleep quality, impaired daily productivity and decreased mood, highlight a significant yet underrepresented disease burden. Recent advances in tear-based multi-omics have enabled detailed characterisation of OA-associated biochemical changes on the ocular surface, highlighting human tears as a promising biospecimen for diagnostic biomarker and therapeutic target research. This review discusses emerging proteomic, lipidomic, metabolomic and miRNA findings comparing OA sufferers with healthy controls, and, where relevant, with comorbid conditions such as dry eye disease and keratoconus. Differential expression patterns across these analytes implicate key pathways involved in immune response, wound healing, angiogenesis, inflammation, oxidative stress and return to homeostasis on the ocular surface. By integrating these data into a stepwise model of OA biopathway activation, this review outlines candidate biomarkers and highlights methodological advances that may support translation of tear multi-omics into clinical tools for OA management. Full article

Cardiac fibrosis is a major component of heart failure (HF) and develops when reparative wound healing becomes chronic, leading to excessive extracellular matrix accumulation. Cardiac fibroblasts (CFs), the main regulators of matrix remodeling, are heterogeneous in developmental origins, regional localizations, and activation states. This diversity determines whether tissue repair resolves normally or progresses into maladaptive scarring that disrupts myocardial structure and function after injuries. Recent single-cell and spatial transcriptomic studies show that CFs exist in distinct yet interrelated molecular states in murine models and human cardiac tissue with specialized roles in matrix production, angiogenesis, immune signaling, and mechanical sensing. These insights redefine cardiac fibrosis as a dynamic and context-dependent process rather than a uniform cellular response. Although CFs are promising targets for preventing HF progression and enhancing cardiac remodeling, translation into effective therapies remains limited by the unclear heterogeneity of pathological fibroblasts, the lack of distinctive CF markers, and the broad activity of fibrogenic signaling pathways. In this review, we discuss the dynamics of CF activations during the development and progression of HF and assess the underlying pathways and mechanisms contributing to cardiac dysfunction. Additionally, we highlight the potential of targeting CFs for developing therapeutic strategies. These include nonspecific suppression of fibroblast activity and targeted modulation of the signaling pathways and cell populations that sustain chronic remodeling. Furthermore, we assess regenerative approaches that can reprogram fibroblasts or modulate their paracrine functions to restore functional myocardium. Integrating antifibrotic and regenerative strategies with advances in precision drug discovery and gene delivery offers a path toward reversing established fibrosis and achieving recovery in HF. Full article

Sunflower seeds have been reported to be a healthy natural source of polyphenols. This study aimed to explore the mechanisms of potential compounds in sunflower seed extract involved in wound healing; major compounds were investigated through network pharmacology and molecular docking. In an in vitro wound-healing assay applied using an immortalised human keratinocyte (HaCaT) cell model, 10 µg/mL of the sunflower seed extract promoted cell migration in HaCaT cells and led to complete wound closure after 24 h; at a 1 µg/mL concentration, it led to complete wound closure after 72 h. The sunflower seed extract presented moderate-to-strong antioxidant activity. Liquid chromatography–mass spectrometry and high-performance liquid chromatography were used to identify the major compounds present in the sunflower seed extract. Forty-seven compounds were identified, among which chlorogenic acid was the most abundant phenolic compound. Network pharmacology was used to identify wound-healing-related targets. In total, 252 proteins were linked to the 47 compounds. Cyto-Hubba analysis identified 10 hub proteins with a strong correlation with wound healing. Molecular docking was used to assess the ability of the major compounds in the sunflower seed extract to combat NF-κB1, EGFR, and MMP9. Chlorogenic acid showed higher binding affinity to all targets. Moreover, its pharmacokinetic properties were well distributed in the plasma (VDss = 0.377 log L/kg), and they were not a carcinogen and did not cause skin sensitisation. In conclusion, the findings suggest that the sunflower seed extract is a potential source of bioactive compounds that can enhance wound healing and can be developed to create a transdermal application. Full article

The development of functionality in wound dressings has progressed since the discovery by Winter that moist wounds heal more rapidly. Approaches to incorporate functionality on several fronts of wound healing have been targeted. Here, we consider three functional features that have received increased attention for their role in promoting healing in hard-to-heal wounds: control of protease levels, hydrogen peroxide generation, and antibacterial efficacy against multidrug resistance bacteria, the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. We review some clinically employed dressings used to treat chronic and burn wounds that have been characterized by their functional protease-modulating activity and contrast one well-studied analog with a cotton-based technology. Similarly, hydrogen peroxide generation profiles were obtained for dressings in different moist wound healing categories and contrasted with a modified form of a known hemostatic cotton-based technology. We examined ascorbic acid-modified forms of a cotton-based technology used for bleeding control in an ESKAPE antibacterial assessment using the AATCC 100 TM. The results for the cotton-based technology were significant protease uptake, hydrogen peroxide generation capacities at proliferative and antimicrobial levels, and >99.99% efficacy against ESKAPE pathogens. These results reflect the importance of considering new forms of cotton fiber technology for incorporation in advanced wound dressing approaches. Full article

Liver fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) proteins as a wound-healing response to chronic liver injury, leading to tissue scarring and organ dysfunction. Natural compounds, including phytonutrients and polyphenols, have been shown to exert protective effects by reducing profibrotic biomarkers in vitro and in vivo models. Here, we provide the first evidence that the polyphenol hesperidin (HE) can counteract the onset of fibrotic responses in an ex vivo mouse liver fibrosis model induced by Transforming Growth Factor-β1 (TGF-β1) (5 ng/mL). Notably, HE drives early ECM remodeling in the fibrotic mouse liver tissue. Fibrosis-related parameters were assessed at both the transcriptional and translational levels after treatment with HE at increasing concentrations of 50, 75, and 100 µg/mL. Interestingly, HE at 75 µg/mL exerted the strongest beneficial effect, significantly decreasing the gene expression of α-SMA, SERPINH-1, FN-1, VIM and COL1A1 and counteracting the TGF-β1-induced upregulation of key fibrotic markers, including α-SMA, COL1A2, and VIM, reflecting its capacity to attenuate myofibroblast activation and ECM production and modulating membrane lipid peroxidation. Furthermore, HE inhibited SMAD2 phosphorylation, suggesting that its antifibrotic activity may involve the modulation of the TGF-β/SMAD signaling pathway. Moreover, it promoted an anti-inflammatory response, due to a decrease in IL-1β and IL-6 expression. Our study highlights the potential of the ex vivo model as a platform for evaluating the antifibrotic efficacy of natural molecules, and it suggests significant translational implications and new opportunities for developing innovative therapeutic strategies. Full article

Topical antibiotics have long been used for the prevention and treatment of superficial skin and soft tissue infections; however, increasing evidence indicates that their clinical value is undermined by rising antimicrobial resistance, high rates of allergic sensitization, inadequate activity against biofilms, and a lack of wound-healing properties. Agents such as bacitracin, neomycin, polymyxin B, mupirocin, and fusidic acid act through narrow, target-specific mechanisms that facilitate resistance selection and provide limited benefit in chronic or polymicrobial wound environments. Contemporary antimicrobial stewardship frameworks therefore discourage routine use of topical antibiotics and increasingly favor non-antibiotic antiseptics with broad-spectrum activity and low resistance risk, including silver, iodine, polyhexamethylene biguanide, octenidine, and medical-grade honey. These modalities, however, primarily serve to reduce microbial burden and do not directly address the underlying biological impairments that prevent healing. Nitric oxide-releasing gels (NORGs) represent a novel class of topical antimicrobials that combine multi-target bactericidal activity with physiologic pro-healing effects. Nitric oxide exerts potent antimicrobial and antibiofilm effects via oxidative and nitrosative stress, disruption of metabolic pathways, inhibition of DNA replication, and interference with quorum sensing. Simultaneously, nitric oxide enhances angiogenesis, modulates inflammation, improves microvascular perfusion, and promotes fibroblast and keratinocyte function. Preclinical models and early-phase clinical studies demonstrate broad-spectrum efficacy—including activity against multidrug-resistant organisms—with favorable tolerability and minimal risk of resistance development. Although the current evidence base remains preliminary, NORGs offer a promising antimicrobial platform with the potential to reduce reliance on topical antibiotics while simultaneously addressing key barriers to wound healing. Larger randomized controlled trials, direct comparisons with established advanced dressings, and robust pharmacoeconomic evaluations are needed to define their optimal role within stewardship-aligned wound-care practice. Full article

The genus Plantago (Plantaginaceae) is widely distributed worldwide. The Plantago species are used in traditional medicine as wound healers, anti-inflammatory agents, antipyretics, and analgesics. This study aimed to investigate the phytochemical composition from the aerial parts of Plantago indica L. and to evaluate its biological activities. Isolation studies and in vitro investigations were conducted on an aqueous phase of 80% EtOH extract of Plantago indica. In addition, in vivo studies were carried out using the MeOH, 80% EtOH, and water extracts. Plantarenaloside (1), 3-oxo-α-ionol β-glucoside (2), martynoside (3), acteoside (4), feruloyl gardoside (5), and ursolic acid (6) were isolated from the extract. The structures of the compounds were elucidated using 1D- and 2D-NMR and ESI-MS analyses. The extract, fractions, and pure compounds were tested in vitro for cytotoxicity (MTT), anti-inflammatory activity (NO, IL-6, and TNF-α production), wound healing (scratch test), and antioxidant capacity (DPPH, ABTS, SO). Feruloyl gardoside (20.11–58.27%) significantly reduced NO levels at concentrations of 25–100 µM. It significantly reduced IL-6 levels (40.17%) at 100 µM. Additionally, the in vivo anti-inflammatory (acetic acid-induced vascular permeability) and wound healing (incision and excision models) effects of the extracts were investigated. The findings suggest that P. indica may be considered to be a potential therapeutic option for managing inflammation and for promoting wound healing. Full article

Ultra-short peptides (USPs; ≤7–8 amino acids) emerge as minimal self-assembling building blocks for hydrogel-based biomaterials. Their intrinsic biocompatibility, straightforward synthesis, and ease of tunability make them particularly attractive candidates for potential use in bioprinting. This review provides an overview of the properties of USPs along with their applications in three-dimensional (3D) bioprinting. We first discuss how peptide sequence, terminal and side-chain modifications, and environmental triggers govern USPs’ self-assembly into nanofibers and 3D networks and how these supramolecular features translate into key rheological properties such as shear-thinning, rapid gelation, and mechanical tunability. We then survey reported applications in tissue engineering, wound healing, and organotypic models, as well as emerging ultra-short peptide-based systems for drug delivery, biosensing, and imaging, highlighting examples where printed constructs support cell viability, differentiation, and matrix deposition. Attention is given to hybrid and multi-material formulations in which USPs provide bioactivity while complementary components contribute structural robustness or additional functionality. Finally, this review outlines the main challenges that currently limit widespread adoption, including achieving high print fidelity with cytocompatible crosslinking, controlling batch-to-batch variability, and addressing the scalability, cost, and sustainability of peptide manufacturing. We conclude by discussing future opportunities such as AI-assisted peptide design, adaptive and multi-material bioprinting workflows, and greener synthetic routes, which together may accelerate the translation of ultra-short peptide-based bioinks from proof-of-concept studies to clinically and industrially relevant platforms. Full article

Wound healing is a complex, multi-phase process requiring coordinated interactions among diverse cell types and molecular pathways to restore tissue integrity. Dysregulation can lead to chronic non-healing wounds or excessive scarring, posing major clinical and economic burdens. Single-omics interrogate individual molecular layers, such as the genome, transcriptome, proteome, metabolome, or epigenome, and have revealed key cellular players, but provide a limited view of dynamic wound repair. Single-cell technologies provide higher resolution to single-omic data by resolving cell-type and state-specific heterogeneity, enabling precise characterization of cellular populations. Multi-omics integrates multiple molecular layers at single-cell resolution, reconstructing regulatory networks, epigenetic landscapes, and cell–cell interactions underlying healing outcomes. Recent advances in single-cell and spatial multi-omics have revealed fibroblast subpopulations with distinct fibrotic or regenerative roles and immune–epithelial interactions critical for re-epithelialization. Integration with computational tools and artificial intelligence (AI) continues to reveal cellular interactions, predict healing outcomes, and guide development of personalized therapies. Despite technical and translational challenges, including data integration and cost, multi-omics are increasingly shaping the future of precision wound care. This review highlights how multi-omics is redefining understanding of wound biology and fibrosis and explores emerging applications such as smart biosensors and predictive models with potential to transform wound care. Full article

Antimicrobial peptides (AMPs) have been shown to have pro-angiogenic activity, capable of enhancing neovascularization and facilitating the healing of chronic wounds. However, information as such remains rather limited. Here we clearly showed that the fish phosvitin-derived AMP Pt5-1c was able to enhance angiogenesis in both murine full-thickness wound models and zebrafish with vascular defects models. We also showed that Pt5-1c was able to promote endothelial cell motility, adhesion, survival, filopodia protrusion, and induce endothelial tube formation. In addition, we found that Pt5-1c could upregulate production of proangiogenic factors including VEGF, PDGF, FGF and EGF. It was revealed that Pt5-1c promoted endothelial cell motility, growth and survival via activation both PI3K/AKT/mTOR and p38 MAPK pathways as well as HIF-1-VEGF axis. It is apparent that Pt5-1c is a novel candidate of pro-angiogenic agents for vascular regenerative therapy. Full article

Diabetic wounds are typically difficult to heal. They are usually characterized by prolonged healing time and increased susceptibility to bacterial infection. Therefore, altering the wound microenvironment and improving antibacterial property are effective treatment strategies. In this study, a plant hydrogel with antimicrobial activity and pro-healing properties was designed to integrate silver nanoparticles (AgNPs) with antimicrobial activity into the natural Tofu Chai (Premna microphylla Turcz, PMT) hydrogel, which exhibits strong pro-healing ability and antibacterial infections on the wound surface. In vitro experiments showed that AgNPs-PMT had a significant killing effect on Methicillin-resistant Staphylococcus aureus (MRSA), with an antibacterial efficiency reaching 95.6%. In vivo results showed that AgNPs-PMT efficiently cleared bacteria at the wound site to promote the formation of neovascularization, collagen and granulation tissue, and facilitated wound healing in a diabetic wound model with MRSA infection. On the 11th day, the wound area was only 5.4% of its original size. Overall, AgNPs-PMT demonstrated favorable antibacterial effects against MRSA and showed great potential in the treatment of chronic diabetic wounds. Full article

Background: Frostbite injury creates an ischemic, hypoxic, and acidic microenvironment that often triggers severe oxidative stress and inflammation. Current therapeutic approaches are limited by low drug delivery efficiency and an inability to adequately regulate multiple pathological pathways. Although oxyresveratrol (OR) exhibits excellent antioxidant and anti-inflammatory activities, its application is hampered by poor aqueous solubility and low stability. Methods: We constructed Oxyresveratrol@Zeolitic Imidazolate Framework-8 nanoparticles (OR@ZIF-8) and further embedded them in a sodium hyaluronate (HA) matrix to form an OR@ZIF-8@HA composite hydrogel. The physicochemical properties and pH-responsive drug release behavior of the system were characterized. Its antioxidant activity, ability to promote cell migration, and capacity to modulate macrophage polarization were evaluated in cellular assays. The therapeutic efficacy was further investigated using a mouse frostbite model, with wound repair analyzed via histological staining. Results: The OR@ZIF-8 nanoparticles achieved a cumulative release rate of 75.46 ± 3.68% under acidic conditions within 36 h. In vitro experiments demonstrated that the formulation significantly scavenged TNF-α and IL-6, by 161.85 ± 19.43% and 125.37 ± 12.65%, respectively, and increased the level of IL-10 by 44.97 ± 4.57%. In a scratch assay, it promoted wound healing, achieving a closure rate of 97.55 ± 2.77% after 36 h. In vivo studies revealed that the OR@ZIF-8@HA treatment group achieved a wound healing rate of 96.14 ± 4.12% on day 14. Conclusions: The OR@ZIF-8@HA composite hydrogel effectively overcomes the limitations of OR application via intelligent pH-responsive delivery. Through synergistic multi-mechanistic actions, it significantly accelerates frostbite wound healing, offering a novel and efficient therapeutic strategy for frostbite management. Full article

Background/Objectives: Burn injuries pose a significant challenge due to tissue damage and impaired healing. Cell-based therapies offer promise by delivering therapeutic cells to the wound site. However, effective cell delivery remains a critical hurdle. This study investigates the potential of non-crosslinked hyaluronic acid (HA) as a simple, versatile carrier for delivering autologous keratinocytes and fibroblasts to treat early burn wounds. Methods: Primary keratinocytes and fibroblasts were isolated from uninjured adult skin. In addition, fibroblasts and adipose stem cells (ASC) from polydactyly and progenitor fibroblasts were used. Non-cross-linked HA Redensity 1^® (RD1) solutions of varying concentrations were prepared and applied to various in vitro models. Cell viability, proliferation, migration, and collagen stimulation were assessed using standard assays. Additionally, cells were suspended in Redensity 1 and applied to an in vitro de-epidemalized dermis (DED) wound model to examine cell delivery and tissue reformation. Results: Preliminary data demonstrated the feasibility of using non-cross-linked HA RD1 gel as a cell carrier. RD1 gel enhanced cell viability, retention, migration, and collagen deposition. Histological analysis revealed improved cell adhesion and migration. Conclusions: This study provides valuable insight into the potential of non-cross-linked HA RD1 as a simple and effective delivery vehicle for cell therapies in early burn care. Successful translation of this approach could significantly improve clinical outcomes for burn patients. Full article

Chronic liver disease (CLD) encompasses a spectrum of progressive disorders, including metabolic dysfunction steatotic-associated liver disease (MASLD) and primary biliary cholangitis (PBC), which together represent a significant global health burden with few effective therapeutic options. The fibrogenic process, common to most forms of CLD, is driven by a complex interplay of cellular stress, inflammation, and wound-healing responses. Nicotinamide adenine dinucleotide phosphate oxidase isoforms 1 and 4 (NOX1 and NOX4) have emerged as key enzymatic sources of reactive oxygen species (ROS), serving as central mediators of hepatic oxidative stress, fibrogenesis, and inflammation. Setanaxib is a first-in-class, orally bioavailable, selective dual inhibitor of NOX1 and NOX4 that has progressed to clinical evaluation. This review synthesizes current knowledge on the molecular pharmacology of the NOX1/4 axis, preclinical evidence from translational models, and clinical trial outcomes to critically assess the therapeutic potential of targeted NOX inhibition in hepatic fibrosis. By attenuating hepatic stellate cell activation, modulating TGF-β signaling, reducing extracellular matrix (ECM) deposition, and regulating hepatic macrophage polarization, setanaxib exhibits pleiotropic antifibrotic effects. The compound also demonstrates favorable pharmacokinetic properties and a good safety profile in patients with PBC, with emerging evidence suggesting meaningful improvements in fatigue and quality of life. Finally, we examine the complex, and sometimes paradoxical, roles of NOX4 in liver pathophysiology, compare the evolving therapeutic landscape with other approaches such as farnesoid X receptor (FXR) agonists, and propose future paradigms integrating artificial intelligence–driven predictive modeling to optimize patient stratification and therapeutic response in this new era of redox-targeted hepatoprotective therapy. Full article