Search Results (549)

Traditionally, chronic wounds including diabetic foot ulcers (DFUs), pressure ulcers (PUs), venous leg ulcers (VLUs), arterial ulcers, inflammatory and autoimmune-associated ulcers, infected chronic wounds, and non-healing post-surgical wounds are treated as localized diseases of skin and soft tissue damage. However, these lesions are increasingly acknowledged as chronic inflammatory states with consequences extending beyond the wound bed and often arising in the setting of systemic dysfunction. Across wound types, shared features include persistent inflammation, oxidative stress, endothelial dysfunction, immune imbalance, protease dysregulation, infection or biofilm burden, metabolic disturbance, and impaired regenerative signaling. These abnormalities may promote systemic cytokine release, vascular dysfunction, neurohumoral activation, oxidative injury, and maladaptive remodeling. Cardiac dysfunction is already known to impair wound healing. In contrast, whether chronic non-healing wounds are associated with or may contribute to cardiac damage resulting in heart failure remains insufficiently defined. Emerging epidemiologic and mechanistic evidence suggests that chronic non-healing wounds may amplify cardiovascular stress, particularly in vulnerable patients with diabetes, obesity, frailty, kidney disease, or pre-existing vascular disease. This narrative review explores the conceptual hypothesis that chronic non-healing wounds may contribute to systemic cardiovascular stress and cardiac dysfunction. It integrates clinical and mechanistic opportunities, outlines potential pathways, including extracellular vesicle (EV) signaling, and highlights key knowledge gaps and therapeutic implications in the wound–heart axis. Full article

Whilst early debridement and autologous skin grafting remain the cornerstones of treatment for deep burns, there has been a shift towards a more selective and regenerative medicine-oriented approach in the topical management of burn wounds. The most critical issue is whether the wound can achieve epithelialization within approximately 2 to 3 weeks. This timeframe is of clinical significance due to the strong association between delayed epithelialization and hypertrophic scarring, which can result in contractures and functional impairment. However, given that the likelihood of epithelialization is influenced by factors such as the mechanism of injury, anatomical location and skin thickness at that site, age, and blood flow, its prediction remains incomplete and relies heavily on experience. The second challenge is to remove necrotic tissue while preserving as much healthy tissue as possible, thereby creating a wound bed with an adequately controlled microbial burden. Excessive excision should be avoided. The cytotoxic effects of several topical antimicrobial agents can inhibit the migration of keratinocytes, fibroblasts and other cells, as well as damaging the extracellular matrix. In order to address these issues, a range of methods are employed, including enzymatic debridement. The third challenge pertains to the reconstruction of the dermis in full-thickness burns, and the role of dermal and matrix-based materials is expanding. In addition to conventional artificial dermis, acellular fish skin matrices, synthetic biodegradable temporary matrices, and recombinant biomaterials are now being used. These materials can be regarded not solely as wound dressings, but also as instruments for preserving or re-establishing a biologically functional dermal matrix prior to epithelialization. Once these conditions are achieved, autologous skin cell suspension or cultured epidermal autografting may become appropriate options in selected wounds. This Perspective proposes a framework for precision-oriented local burn wound care structured around four sequential but iterative objectives. Full article

Diabetic foot ulcers (DFU) are among the most severe complications of diabetes, resulting from a combination of metabolic dysregulation, vascular insufficiency, neuropathy, chronic inflammation, and impaired tissue repair, whereas diabetic foot infection (DFI) may develop within this compromised wound environment and frequently involves polymicrobial communities and biofilms. This review evaluates the mechanistic and translational basis for the use of antimicrobial peptides (AMP) in DFU and DFI, with emphasis on the diabetic wound microenvironment, polymicrobial ecology, endogenous AMP dysregulation, mechanisms of action, therapeutic development, and barriers to clinical translation. Hyperglycemia, ischemia, oxidative and proteolytic stress, and impaired innate immunity sustain inflammation, delay tissue repair, and promote microbial persistence. These conditions may also complicate antibiotic treatment through impaired tissue exposure and biofilm-associated tolerance. Depending on the peptide and experimental context, AMP may provide direct antimicrobial or antibiofilm activity and may also exert immunomodulatory or pro-reparative effects involving inflammatory signaling, angiogenesis, keratinocyte and fibroblast migration, and re-epithelialization. Approaches under investigation include engineered peptides, combination regimens, and local biomaterial-based platforms, including hydrogels, dressings, scaffolds, and nanoparticle-conjugated systems. Clinical translation remains constrained by proteolytic instability, potential host-tissue toxicity, limited selectivity, limited predictive value of preclinical models, heterogeneous clinical populations, nonstandardized endpoints, and manufacturing and regulatory requirements. Preclinical evidence supports further evaluation of approaches for local delivery of AMP, whereas clinical evidence in DFU and DFI remains limited and heterogeneous, with no AMP-based intervention yet demonstrating sufficiently consistent clinical benefit to support routine use. Full article

Background/Objectives: Skin and soft tissue infections (SSTIs) remain a major clinical challenge due to the increasing prevalence of antimicrobial resistance and biofilm-associated pathogens. Conventional antibiotics are often limited by reduced efficacy, recurrent infections, and disruption of the resident skin microbiota. Consequently, bacteriocins have emerged as promising alternative or adjunctive antimicrobial agents for the treatment of skin and wound infections. Methods: A literature review was conducted using the PubMed, Scopus, and Web of Science databases. Experimental in vitro, ex vivo, and in vivo studies investigating bacteriocins in skin and wound infection models were analyzed, with a focus on antimicrobial activity, antibiofilm efficacy, activity against antimicrobial-resistant pathogens, and formulation strategies designed to improve therapeutic performance. Results: Available evidence demonstrates that numerous bacteriocins exhibit potent antimicrobial activity against clinically relevant skin-associated pathogens, particularly Staphylococcus aureus, including methicillin-resistant strains (MRSA). Several bacteriocins also showed significant antibiofilm properties and synergistic interactions with conventional antibiotics, resulting in enhanced bacterial eradication and reduced risk of resistance development. Experimental infection models further support their therapeutic potential in wound-associated infections. Additionally, advanced delivery platforms, including hydrogels, wound dressings, nanofibers, and lipid-based nanoparticles, improved peptide stability, sustained release, and local antimicrobial efficacy. Conclusions: Bacteriocins are promising candidates for the prevention and treatment of skin and wound infections due to their antimicrobial and antibiofilm activity, low propensity for resistance development, and suitability for topical administration. However, further studies addressing formulation optimization, safety, pharmacokinetics, and clinical validation are required before bacteriocin-based therapies can enter routine clinical practice. Full article

Diabetic refractory wounds are a prevalent and severe complication of diabetes, whose pathological progression is jointly mediated by multiple factors, including oxidative stress imbalance, chronic inflammation, impaired angiogenesis, bacterial infection, and biofilm formation. Current clinical hydrogel dressings generally suffer from drawbacks such as single-function performance, potential toxicity of nano-components, static networks incompatible with dynamic wound conditions, and the absence of bionic repair signals. Therefore, they cannot simultaneously satisfy the dual repair requirements of complex pathological microenvironments and dynamic mechanical properties for diabetic wounds. In this study, a multi-functional dynamically responsive composite hydrogel (MC group) with high-efficiency antioxidant, antibacterial, and pro-angiogenic capacities was fabricated. Using SDS-C₁₈ micelles as hydrophobic units, a rigid–flexible dual-network framework was constructed with polyvinyl alcohol (PVA) and methacrylated hyaluronic acid (HAMA). Manganese dioxide nanozymes were introduced to scavenge reactive oxygen species (ROS) and mitigate oxidative stress. Calcium-ion-mediated dynamic micelle reconstruction was adopted to regulate the hydrophilic–hydrophobic balance, while achieving antibacterial effects and facilitating tissue regeneration. In vitro experiments verified that the MC hydrogel possesses mechanical properties well-matched to human soft tissues (fracture stress: 25 kPa) and excellent biocompatibility (cell viability > 100%, hemolysis rate: only 0.13%). It also exhibits prominent antioxidant activity (DPPH radical-scavenging rate: 36.95%), antibacterial performance (>99.86% bactericidal rate against Staphylococcus aureus, survival rate of Escherichia coli reduced to 15.95%), and cell-migration-promoting activity (endothelial cell migration rate of 83.72% and mouse fibroblast migration rate of 90.88% within 24 h). In the full-thickness skin defect model of diabetic mice, the wound-healing rate reached 99% on day 16. Moreover, it promoted ordered collagen deposition, skin appendage regeneration, and functional microvascular reconstruction, thereby accomplishing high-quality tissue repair. This design synergistically intervenes in multiple pathological links of diabetic wounds, overcomes several key limitations of existing dressings, and provides an innovative strategy for developing smart dressings. Full article

Objectives: The study determined antimicrobial resistance profiles of surgical wound multidrug-resistant (MDR) isolates belonging to the ESKAPE group and evaluated antibacterial and antibiofilm activities of geraniol (G), carvacrol (C) and eugenol (E), individually and in the selected mixtures. The cytotoxicity of monoterpenes and combinations was also assessed. Methods: The antibacterial and antibiofilm activity against tested isolates of Enterococcus faecium, Staphylococcus aureus MRSA, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter sp. was assessed in microdilution and crystal violet assay, respectively, while cytotoxicity was estimated in XTT assay on human MRC-5 fibroblasts. Results: C showed the strongest antibacterial activity (MIC 0.32 ± 0.24 mg mL⁻¹). Monoterpenes induced synergism in certain combinations (FICI 0.09–0.31). All individual monoterpenes inhibited biofilm formation, but G was the most active (38.78–84.72%, p < 0.05). The most pronounced biofilm eradication was observed for C (25.21–61.34%, p < 0.05). G-C mixtures showed notable inhibition of biofilm formation in all isolates except P. aeruginosa, but, on the contrary, induced biofilm eradication against P. aeruginosa only. Cytotoxicity was not detected with the applied concentrations of monoterpenes, while the G-C mixtures exhibited lower cytotoxicity than povidone-iodine (p < 0.05) used as the control. Conclusions: All monoterpenes and G-C mixtures proved significant antibacterial and antibiofilm potential against ESKAPE isolates and acceptable impact on cell viability. Practical significance: The results highlight the potential of plant monoterpenes and their binary combinations as complementary agents for controlling MDR ESKAPE pathogens and biofilm-associated infections following surgical procedures. Further in vivo and safety studies are needed to confirm their applicability in clinical settings. Full article

Bacterial infection, biofilm formation, and the associated oxidative stress and persistent inflammation represent major obstacles to wound healing, tissue engineering, and implantable medical devices. Owing to their highly hydrated three-dimensional networks, favorable tissue compatibility, and versatile capacity for functional loading, hydrogels have been widely investigated for the treatment of infected wounds. This review systematically summarizes the major antibacterial mechanisms of hydrogels, including cationic contact-killing, chemical antibacterial activity mediated by metal ions and reactive halogen species, nanozyme-catalyzed reactions and bidirectional regulation of reactive oxygen species, as well as photothermal synergistic antibacterial therapy. Key design strategies are also discussed, including natural polymer-based matrices, multiple dynamic crosslinking, stimuli-responsive controlled release, three-dimensional printing, and spatial compartmentalization. In addition, recent advances in infection-microenvironment regulation, wet-interface adaptation, temporally coordinated tissue repair, and integrated diagnosis and therapy are highlighted. The field is currently shifting from single-mode bacterial eradication toward multistage tissue repair and intelligent theranostics. However, major challenges remain, including balancing antibacterial efficacy with biosafety, achieving reproducible manufacturing and sterilization-compatible formulations, maintaining functional stability during storage, and improving the clinical relevance and standardization of preclinical evaluation. In addition, most smart systems still lack quantitative coupling among pathological signals, therapeutic dosage, and treatment outcomes. Future studies should therefore integrate mechanistic design with manufacturing reproducibility, clinically relevant validation, and quantitative feedback regulation, thereby advancing antibacterial hydrogels from multifunctional proof-of-concept systems toward precise, controllable, and clinically translatable therapeutic platforms. Full article

Silk fibroin (SF)- and silk sericin (SS)-based antibacterial hydrogels are increasingly engineered as local antimicrobial platforms, yet cross-study interpretation is limited by inconsistent material reporting and by conflation of bacterial inhibition with tissue repair. We performed a structured evidence-mapping and critical synthesis of a frozen 2020–July 2026 corpus of 94 references. The original 46-record core map was re-audited at the original-article level: 43 full-text-verified, non-retracted primary studies were retained for detailed evidence grading, 2 records available only at abstract/database level were retained descriptively but not graded, and 1 subsequently retracted study was excluded from quantitative synthesis. Among the 43 graded studies, metal-ion/nanozyme/catalytic systems were most common (12/43, 27.9%), followed by release-mediated (11/43, 25.6%), multimodal (9/43, 20.9%), contact-active/anti-adhesive (6/43, 14.0%), and light-responsive systems (5/43, 11.6%). Sixteen studies (37.2%) used deliberately infected animal models, whereas only 4 (9.3%) reached a biofilm or adherent-bacteria-level endpoint in the graded map. Biological claim ceilings (C0–C5) are assessed independently from translation gates spanning material identity, reproducibility, mechanism, host safety, sterilization/storage, resistance, long-term fate, and deployment. Across mechanisms, SF and SS most often function as structural, interfacial, or transport-regulating matrices; direct silk-dependent bactericidal causality remains uncommon. The central translational deficit is failure to quantitatively link silk molecular identity and network architecture to antimicrobial exposure, bacterial killing, host selectivity, and long-term material fate. Full article

Burns injuries present critical health and care challenges and remain one of the leading causes of preventable morbidity globally. The pathophysiology of burns injuries combines barrier disruption, dysregulated inflammation and biofilm-driven polymicrobial infection. Zinc oxide nanoparticles (ZnO NP) offer unique, multi-functional capabilities of broad-spectrum antimicrobial, pro-regenerative zinc (II) ion sources and an intrinsic transducer that is piezoelectric, photoresponsive and pH-responsive. This paper presents a comprehensive review of ZnO NP for the treatment of skin burns injuries with a focus on its multifunctional nanotherapeutic and sensor-integrated platforms. A structured literature search of PubMed, Scopus, Web of Science, Embase and IEEE Xplore covering the period 2015 to 2025 was conducted to identify and consolidate relevant pre-clinical and clinical evidence on ZnO-based and sensor-integrated burn wound platforms. From the survey across hydrogels, electrospun nanofibers, films, sprays, and three-dimensional bio-printed constructs, it is established that ZnO formulations achieve 60–95% wound closure by day 14 versus 30–55% for untreated controls, with 3–7 log10 colony-forming-unit reductions and minimum inhibitory concentrations of 8–256 micrograms per millilitre against multidrug-resistant pathogens. Wound healing is driven by sustained Zn²⁺ release, reactive-oxygen-species-mediated bactericidal action, matrix-metalloproteinase-9 modulation, vascular-endothelial-growth-factor and hypoxia-inducible-factor-1-alpha angiogenesis, and nuclear-factor-kappa-B suppressed inflammation. Emerging closed-loop sensor-integrated dressings deliver real-time wound pH, temperature, and matrix-metalloproteinase-9 readout coupled to near-field-communication actuated on-demand zinc release. Clinical translation is affected by several factors such as dose-dependent cytotoxicity associated with excessive ROS generation or dissolution, limited standardisation of green-synthesis methodologies, batch-to-batch variability in nanoparticle physicochemical properties and limited clinical trial data. ZnO-based theranostic platforms hold practical clinical translation potentials provided reproducible GMP-scale synthesis, long-term biocompatibility validation and comprehensive regulatory classification is systematically addressed. Full article

Chronic ulcers require prolonged care and carry an increased risk of infection and limb loss. Sequencing studies of diabetic foot ulcers, venous leg ulcers, and pressure ulcers have revealed dynamic, patient-specific microbial communities whose composition varies with local tissue conditions and treatment exposure. This review examines changes in microbial burden and community structure during wound-bed and antimicrobial interventions and their relationships with healing. Observed shifts may contribute to therapeutic effects, reflect direct perturbation of the community, or follow tissue recovery. However, most studies are small, heterogeneous, and uncontrolled, limiting causal inference. No published randomized trial has shown that treatment selection informed by sequencing-based microbial profiling improves wound healing. A central translational challenge is to determine whether baseline microbial features reproducibly predict responses to defined interventions. Progress will therefore require prospective longitudinal studies integrating sequencing with quantitative culture, isolate phenotyping, antimicrobial susceptibility testing, biofilm assays, and standardized clinical data. Such studies should establish whether microbiome profiling adds clinically useful information to conventional wound assessment and microbiological testing. Full article

Chronic wounds are complex environments marked by persistent inflammation, oxidative stress, hypoxia, and conditions that favor antimicrobial resistance (AMR). Conventional antibiotics often fail due to bacterial persistence and the physicochemical barriers of the wound milieu. Biofilm-associated extracellular polymeric substances (EPS), efflux pump activity, quorum sensing (QS), and horizontal gene transfer (HGT) collectively drive antimicrobial tolerance and resistance dissemination, turning chronic wounds into reservoirs of multidrug-resistant pathogens. Consequently, emerging wound therapies demand multifunctional strategies that modulate the wound microenvironment while interfering with resistance-associated phenotypes. Hydrogel–metal–organic framework (MOF) composites have been explored as multifunctional interfaces that combine extracellular matrix-mimetic properties, tunable porosity, stimuli-responsiveness, and controlled therapeutic delivery with the bioactive functions of MOFs. Depending on their composition and architecture, these systems may exert antimicrobial and antibiofilm effects through ionic, electrostatic, osmotic, catalytic, and oxidative mechanisms, while also influencing ROS levels, inflammation, angiogenesis, and local drug transport. However, antimicrobial activity alone does not equate to resistance modulation. Evidence for direct effects on efflux systems, resistance phenotypes, or HGT remains inconsistent across reported platforms. This review critically examines representative hydrogel–MOF systems for chronic wound applications, comparing their composition, physicochemical properties, biological functions, proposed resistance-related mechanisms, advantages, limitations, and current level of evidence. We emphasize distinguishing experimentally demonstrated resistance-modulating effects from mechanistically proposed functions, and identifying design trade-offs and evidence gaps that must be addressed to develop wound interfaces capable of both supporting tissue regeneration and improving infection control. Full article

Implant-associated infections (IAIs) persist as a critical complication in biomaterial transplantation, driven by rapid microbial colonization, biofilm encapsulation, and escalating antibiotic resistance. Conventional antibiotic-based treatments and passive antimicrobial coatings often fail to achieve long-term infection control due to limited biofilm penetration, localized cytotoxicity, and active agent depletion. To overcome these limitations, piezoelectric nanocomposite coatings utilize a dynamic, stimulus-responsive framework that converts physiological mechanical forces or external ultrasound into localized electrical signals. These surface-bound electric fields systematically mitigate bacterial adhesion, eradicate mature biofilms via targeted reactive oxygen species (ROS) generation, disrupt microbial metabolic pathways, and favorably modulate the peri-implant immune microenvironment while supporting host tissue repair. This review evaluates the material design principles and classifications of inorganic, organic, and hybrid piezoelectric nanocoatings. We detail their multifaceted antibacterial mechanisms and trace their therapeutic potential in orthopedic and dental implants, as well as wound management. Lastly, we analyze current engineering bottlenecks to chart a clear trajectory for their clinical translation. Full article

Background: Lower limb exoprostheses often lead to stump dermatological pathologies. The mechanisms by which mechanical microtraumas progress to non-healing ulcerative defects due to dysbiosis remain poorly understood. The objective of this study was to analyze mechanical, inflammatory, and infectious stump skin complications and justify the role of bacterial and mycological dysbiosis in blocking tissue regeneration. Methods: A critical narrative review guided by SANRA principles was conducted (PubMed/Scopus, 1980–2026). Data were extracted with a structured query focusing on amputation stumps, prosthetic interfaces, and skin/microbiological complications (dysbiosis, biofilms, and inflammatory markers). Evidence was graded using predefined clinical matrices and integrated through structured evidence collations to synthesize stump–prosthesis pathogenesis. The PRISMA method was not applied due to study heterogeneity. Results: Skin damage dynamics were categorized into three stages: adaptation (up to 12 months), chronic reactive changes (12–24 months), and late proliferative-infectious destruction (>24 months). The sealed liner space creates 100% humidity and alkalization (pH > 6.5). This causes a mycological shift, where resident Malassezia spp. lose dominance to invasive Candida albicans and non-dermatophyte molds (Aspergillus spp., Fusarium spp.). These pathogens form polymicrobial biofilms with Staphylococcus aureus. At the molecular level, delayed regeneration is driven by “frustrated phagocytosis”: macrophages, unable to engulf large fungal hyphae, continuously release reactive oxygen species and enzymes, trapping the wound in the inflammatory phase. Excessive matrix degradation and suppressed angiogenic factors further block epithelialization. Conclusions: The skin under a prosthesis socket forms a unique pathological biotope. Successful regeneration requires preventive mycobiota correction and targeted management of biophysical parameters (pH, humidity) within the “skin–liner” interface. Full article

Plant-mediated green synthesis of silver nanoparticles (AgNPs) predominantly relies on single botanical sources, constraining reduction efficiency and forfeiting the therapeutic potential of residual biomass. This study employed aloe vera and birch bark extracts as reducing agents. A combination of single-factor analysis and response surface methodology was employed to prepare monodisperse 30 nm AgNPs (with a Zeta potential of −35.3 mV and confirmed by XPS as metallic Ag⁰). It was loaded into carboxymethyl chitosan-vanillin-polyvinyl alcohol (CVP) gel microneedles using the vacuum casting method. The mechanical strength of these microneedles reaches 0.302 N/needle, exceeding the skin penetration threshold. Throughout the entire preparation process, both its Ag⁰ chemical state and crystal structure were maintained (by FT-IR and XRD). The MIC values of AgNPs@CVP against four pathogens ranged from 0.977 to 7.813 μg/mL, with a biofilm disruption rate exceeding 70%, and demonstrated excellent biocompatibility (hemolytic rate < 1.6%, cell survival rate > 80%). In a rat wound infection model, high-dose microneedle therapy reduced the residual wound area to 10.9% by day 9. This strategy inhibited the secretion of TNF-α and IL-6 while promoting epithelial regeneration, angiogenesis, and collagen deposition. This bifunctional Aloe-Birch strategy converges green nanomaterial synthesis with therapeutic delivery within a single bio-based platform, advancing sustainable nanomedicine paradigms and providing a resource-efficient blueprint for clinical infectious wound management. Full article

Poor aqueous solubility remains one of the most persistent challenges in pharmaceutical development, limiting clinical translation and requiring innovative formulation strategies; approximately 40% of newly discovered pharmaceutical compounds are affected, underscoring the scale of the problem. Emulsion-based delivery systems overcome this limitation by maintaining drugs in a dissolved state, increasing absorption surface area, and enabling controlled release; however, conventional emulsions face thermodynamic instability and coalescence challenges. Cellulose and nanocellulose—cellulose nanocrystals (CNCs), cellulose nanofibers (CNFs), and bacterial cellulose (BC)—have emerged as sustainable, biocompatible alternatives to synthetic surfactants for stabilizing emulsions via Pickering mechanisms involving irreversible adsorption of solid particles at the oil–water interface. This review synthesizes 142 references across eight application themes: fundamentals and history, emulsion templating, drug encapsulation, antimicrobial and pathogen applications, vaccine adjuvants, topical and transdermal delivery, commercial translation, and regulatory gaps. Rather than treating all sources equally, 37 primary studies are examined in depth through structured critical-appraisal tables organized by system type, goal, key result, and limitation; the remainder are synthesized at the pattern level. A key mechanistic distinction is identified between BC as a standalone biomedical material (used in wound dressings, tissue scaffolds, and drug delivery membranes) and BC as a source for Pickering-emulsion stabilizers after disintegration into nanocrystals or nanofibrils. The review’s overall assessment is that the fundamental materials science of cellulose Pickering emulsions is mature and consistent across sources, while the translational evidence, including in vivo confirmation of drug release performance, biofilm-relevant antimicrobial testing, standardized nanocellulose characterization, and up-to-date intellectual property mapping, remains the binding constraint on clinical and commercial adoption. Six specific, evidence-linked research priorities are identified to advance cellulose emulsions toward regulatory approval and clinical use. Full article