Search Results (187)

Background and Objectives: Diabetes mellitus (DM) is a major global health concern, with diabetes-related foot disease (DFD) representing one of its most severe complications, often resulting in chronic infection, osteomyelitis, and limb amputation. Conventional therapies frequently fail in refractory cases, necessitating novel adjunctive strategies. Ozone therapy (OT) possesses antimicrobial, immunomodulatory, and oxygen-enhancing properties, while negative pressure wound therapy (NPWT) facilitates granulation, exudate removal, and tissue perfusion. This study explored the combined efficacy of OT and NPWT in advanced DFD. Materials and Methods: An exploratory, retrospective, observational cohort study was conducted at a specialized wound care center in Gdańsk, Poland, between 2019 and 2022. The study included 30 patients (n = 30) with refractory DFD involving both soft tissue and bone infection who had not responded to previous conventional treatment. The analyzed treatment approach consisted of surgical debridement, application of topical ozonated preparations, and (NPWT) with instillation of ozonated saline administered over a six-week period. Clinical outcomes included wound healing assessed using the Wagner classification and wound volume reduction, pain intensity measured using the Numeric Rating Scale (NRS), inflammatory biomarkers (C-reactive protein [CRP] and procalcitonin [PCT]), and microbiological characteristics of wound cultures. Statistical analyses were performed using the Wilcoxon signed-rank test and the chi-square test, and regression modeling was applied to identify potential predictors of therapeutic response. Statistical significance was defined as p < 0.05. Results: By week six, 100% of ulcers improved to Wagner stage ≤1, with 26.7% achieving stage 0. Median wound volume decreased from 5.5 cm³ to 0 cm³ (p < 0.001). Pain scores declined from 7.2 ± 0.96 points to 0.2 ± 0.5 points (p < 0.001). CRP and PCT levels decreased significantly (p < 0.001), and microbiological clearance was observed in all cases. Higher body mass index (BMI) was associated with poorer pain reduction. Conclusions: The combination of standard wound care with OT and NPWT was associated with clinically relevant improvements in wound healing, infection control, systemic inflammation, and pain reduction in patients with refractory DFD. Although limited by a non-controlled design and small cohort size, these findings support further randomized controlled trials to define the role of this combined approach in integrated diabetic foot care. Full article

As natural nanoscale intercellular messengers, exosomes exhibit considerable potential in modulating inflammation, angiogenesis, immunoregulation, and tissue remodeling, making them attractive candidates for regenerative medicine. However, their clinical translation remains limited by rapid systemic clearance, nonspecific biodistribution, insufficient lesion retention, and functional attenuation in hostile pathological microenvironments. In this review, we propose that biomaterial engineering should evolve from providing passive exosome carriers to constructing active regulatory platforms capable of precise spatiotemporal control. We summarize engineering strategies along two complementary dimensions. In the temporal dimension, biomaterials can enable sustained, sequential, or microenvironment-responsive release to match the dynamic phases of tissue repair. In the spatial dimension, biomaterials can improve local retention, tissue anchoring, structural guidance, endogenous cell recruitment, and lesion-specific delivery. Using cutaneous wound healing, osteochondral regeneration, myocardial repair, and neural regeneration as representative examples, we further analyze these strategies through a “clinical challenge–engineering strategy–biological mechanism” framework, with particular attention to how engineered systems influence key signaling pathways such as PI3K/Akt, Wnt/β-catenin, NF-κB, and PTEN/PI3K/Akt/mTOR. We also discuss translational barriers, including exosome heterogeneity, safety concerns inherited from parental cells, large-scale GMP-compliant manufacturing, product standardization, storage stability, and regulatory classification of exosome–biomaterial hybrids. Finally, we highlight emerging directions, including multi-mechanism combinational systems, closed-loop responsive platforms, and artificial intelligence-assisted design for personalized exosome therapeutics. This review provides a design-oriented framework to accelerate the bench-to-bedside development of biomaterial-enabled precision exosome therapy. Full article

Background/Objectives: Nipple-sparing mastectomy with immediate reconstruction is a preferred option for selected patients undergoing prophylactic or therapeutic mastectomy. Optimizing postoperative wound care is essential to support healing, preserve the nipple–areola complex, and prevent delays in oncologic treatments. This retrospective observational study aimed to evaluate the clinical outcomes associated with the use of the NovoX^® Cup medical device in post-NSM surgical wound management, assessing clinical–surgical outcomes and quality of life (QoL). Methods: We conducted a retrospective observational study on 54 patients who underwent NSM with immediate reconstruction at AOUI Verona between January 2025 and January 2026; Novox^® Cup was applied intraoperatively and changed every 48 h according to protocol. Surgeon-reported outcomes were assessed by the skin flap viability scale and the complications by Clavien–Dindo classification. Patient-reported outcomes were assessed via the Wound-QoL17 questionnaire at 7, 30, and 90 days. Clinical outcomes were supported by photographic documentation. Results: Mean age was 51.5 years; BMI averaged 23.9 kg/m². Local complications occurred in 30.4% of cases (infections 12%, dehiscence 10%, seromas 4%). Mean healing time was 15 days, with 87.4% of patients having drains removed by day 14. One patient required surgical revision, and one (1.8%) experienced delayed adjuvant therapy. Wound-QoL17 responses showed minimal discomfort and high satisfaction. Clinical evaluation revealed favorable wound appearance and preserved NAC perfusion within 48 h. Conclusions: Novox^® Cup appears effective in supporting wound healing and NAC preservation after NSM, with high patient satisfaction and minimal treatment delays. Its integration into postoperative care may enhance outcomes and maintain oncologic timelines. Full article

This study explores Serbia’s rich ethnopharmacological heritage by systematically documenting the traditional use of medicinal plants for treating skin diseases during the 19th and 20th centuries. Drawing on key ethnographic sources—including monographs, scholarly articles, and field reports—the review analyzes historical records of folk medicine practices and their cultural contexts. A total of 164 plant species from 63 botanical families, as well as one mushroom species, were identified as being used in the treatment of skin-related conditions classified according to the International Classification of Primary Care. Reported ailments were grouped into three main categories: hair and scalp disorders, bites, and various inflammatory skin conditions such as eczema and psoriasis. Remedies for wound healing were the most frequently documented, both in terms of application and diversity of plant species employed. By preserving and systematizing this historical knowledge, the study provides a valuable foundation for future pharmacological and dermatological research, highlighting the continued relevance of traditional remedies in modern clinical practice. Full article

Background/Objectives: Wound infections cause significant morbidity, yet current diagnostics rely on time-consuming microbial culture. Volatile organic compounds (VOCs) from bacterial metabolism offer potential for early diagnosis. This study aimed to validate the volatile metabolites profiled by gas chromatography–ion mobility spectrometry (GC-IMS) combined with machine learning for rapid identification of wound infections and certain bacterial infections. Methods: Headspace of clinical wound samples were analyzed using GC-IMS. Volatile metabolite profiles were compared between infected and non-infected groups and between Escherichia coli (E. coli)-positive and negative samples. Partial least squares discriminant analysis (PLS-DA) and Mann–Whitney U test were used for preliminary screening with variable importance in projection (VIP) > 1 and p-value < 0.05. Three machine learning algorithms, namely support vector machine (SVM), logistic regression (LR), and random forest (RF), were trained on the selected features for classification, using 5-fold cross-validation with 10 repeated runs. Model performance was assessed using key evaluation metrics, including accuracy, sensitivity, specificity, the area under the curve (AUC) and feature importance ranking to identify the most relevant biomarkers. Results: A total of 19 volatile metabolites associated with clinical wound samples were identified. The RF model achieved 90.15% sensitivity and 0.91 AUC for bacterial infection detection. For E. coli identification, LR reached 85.35% sensitivity and 0.89 AUC. Potential volatile metabolic biomarkers including elevated 3-methyl-1-butanol, 2-methyl-1-butanol, and ethyl hexanoate for identifying bacterial infection were selected through the cross-validation results of the three algorithms. Conclusions: Untargeted metabolomics by GC-IMS effectively captures infection-specific volatile metabolic signatures in complex wound samples. Integration with machine learning enables rapid, high-accuracy diagnosis of bacterial infections and E. coli identification at point of care. This approach addresses clinical metabolomics translational challenges by providing a portable and cost-effective method, potentially reducing antibiotic misuse through more timely and targeted therapy. Full article

Chronic non-healing wounds, prevalent in diabetic and vascular diseases, arise from dysregulated chemokine signaling that disrupts angiogenesis, immune coordination, and tissue remodeling. This review synthesizes current knowledge on chemokine biology in wound repair, with a focus on their spatiotemporal regulation across the hemostasis, inflammation, proliferation, and remodeling phases. We detail chemokine classification (CC, CXC, CX3C, and C families), receptor interactions, and downstream pathways, including G protein-dependent and β-arrestin-biased mechanisms. Furthermore, we evaluate emerging therapeutic strategies, including neutralizing antibodies, receptor antagonists, engineered chemokines, and biomaterial-based delivery systems designed to restore chemokine gradient integrity and promote healing. Recent advances in structural biology and protein engineering are highlighted as enabling the design of biased ligands and multi-target inhibitors to overcome chemokine redundancy. The review concludes that precision modulation of chemokine networks offers a promising translational framework to redirect chronic inflammation toward regenerative healing, thereby addressing a significant unmet clinical need in chronic wound management. Full article

Guava is a popular fruit in the Philippines, as it offers various health benefits. Its leaves are used in traditional medicine to aid in wound healing, stomach disorders, pain relief, and more. In this study, we classified guava leaf diseases using Support Vector Machine (SVM) and You Only Look Once version 8 (YOLOv8). Raspberry Pi 4 is used to control the image preprocessing and the program that utilizes the proposed trained model. The SVM model conducts image classification, while YOLOv8 handles feature extraction and object detection. Grayscale and color thresholding segmentation feature extraction is also implemented in the proposed model. The developed model combines both YOLOv8 and SVM algorithms to evaluate their accuracy using a confusion matrix, achieving a 92.5% accuracy. With its very low error rate, the system can accurately classify guava leaf diseases. Full article

Chronic wound healing is a complex pathological process driven by multiple factors, presenting a significant global healthcare challenge. It not only severely compromises patients’ quality of life but also imposes a substantial socioeconomic burden. In recent years, with deepening insights into the wound microenvironment, composite therapeutic strategies combining natural herbal medicines and their active components with modern biomaterials have offered novel approaches to overcoming refractory wounds caused by diabetic ulcers, vascular lesions, burns, and infections. This paper first outlines the biological foundations of normal wound healing, emphasizing the core mechanisms underlying chronic wound persistence—including persistent inflammatory responses, impaired tissue repair, and cellular dysfunction. Building upon this foundation, the article systematically reviews the existing therapeutic approaches (such as conventional debridement) before focusing on the classification and application of novel biomaterials. It further analyzes the synergistic therapeutic advantages of using materials as delivery systems for natural bioactive compounds. This combined approach enables targeted regulation of the chronic wound microenvironment, synergistically promoting cell proliferation and migration to accelerate healing. Deepening our understanding of the biological mechanisms underlying chronic wounds, coupled with advanced biomaterial technologies, will propel clinical treatment toward more precise and efficient outcomes. Full article

Bacterial wound infection poses a major challenge in trauma care and can lead to severe complications such as sepsis and organ failure. Therefore, rapid and accurate identification of the pathogen, along with targeted intervention, is of vital importance for improving treatment outcomes and reducing risks. However, current detection methods are still constrained by procedural complexity and long processing times. In this study, a hyperspectral imaging (HSI) acquisition system for bacterial analysis and a multi-scale dual-domain feature fusion transformer (MDF2Former) were developed for classifying wound bacteria. MDF2Former integrates three modules: a multi-scale feature enhancement and fusion module that generates tokens with multi-scale discriminative representations, a spatial–spectral dual-branch attention module that strengthens joint feature modeling, and a frequency and spatial–spectral domain encoding module that captures global and local interactions among tokens through a hierarchical stacking structure, thereby enabling more efficient feature learning. Extensive experiments on our self-constructed HSI dataset of typical wound bacteria demonstrate that MDF2Former achieved outstanding performance across five metrics: Accuracy (91.94%), Precision (92.26%), Recall (91.94%), F1-score (92.01%), and Kappa coefficient (90.73%), surpassing all comparative models. These results have verified the effectiveness of combining HSI with deep learning for bacterial identification, and have highlighted its potential in assisting in the identification of bacterial species and making personalized treatment decisions for wound infections. Full article

Extracellular vesicles (EVs) are membrane-bound nanoparticles released by almost all cell types into the extracellular space, acting as important mediators of intercellular communication by transferring proteins, lipids, and nucleic acids horizontally. EVs are generally classified into small EVs (<200 nm), medium/large EVs (>200 nm), microvesicles, and apoptotic bodies, with current classification methods focusing on physical properties, molecular composition, and cellular origin, as detailed in the MISEV2023 guidelines. EVs are highly promising for diagnostic and therapeutic applications due to their intrinsic biocompatibility, stability in biological fluids, capacity to carry diverse molecular cargo, and potential for drug delivery and functionalization to enable targeted delivery and tissue repair. This narrative review discusses the emerging roles of EVs across various medical fields, including obstetrics and gynecology, ophthalmology, otorhinolaryngology, urology, oncology, orthopedics, neurology, immunology, wound healing, chronic pain management, dermatology, and cardiology. In each discipline, EVs show potential as biomarkers for diagnosing physiological or pathological conditions and as carriers for targeted drug delivery and regenerative treatments. Exosomes, a major type of small EVs, have especially attracted attention as versatile nanocarriers for precision medicine. However, translation into clinical practice requires addressing key pitfalls, including the standardization of isolation and characterization protocols, dose definition, GMP-compliant large-scale production, and regulatory approval. Ongoing interdisciplinary collaboration across disciplines and thorough clinical testing will be essential to unlock the full biomedical potential of EVs and establish them as transformative tools in personalized healthcare. Full article

Metallogels constitute a rapidly expanding class of hybrid soft materials in which metal ions, metal complexes, or metal-containing nanoparticles play a decisive structural and functional role within a three-dimensional gel network. Their unique combination of supramolecular assembly, metal-ligand coordination, and dynamic network behaviour provides tunable mechanical, optical, electrical, redox, and catalytic properties that are not accessible in conventional hydrogels or organogels. This review systematically summarises current knowledge on metallogels, beginning with a classification based on matrix type, dominant metal interaction and functional output, spanning metallohydrogels, metal-organic gels, metal-phenolic gels, nanoparticle-based gels, polymer-based metallogels and low-molecular-weight metallogels. Key synthesis pathways are discussed, including coordination-chemistry-driven formation, metal-ligand self-assembly, in situ reduction, diffusion-mediated strategies, sol-gel-like polymerisation, enzyme-assisted routes, and bio-derived fabrication. Particular emphasis is placed on structure-function relationships that enable the development of catalytic, conductive, luminescent, antimicrobial, and biomedical metallogels. The examples compiled here highlight the versatility and transformative potential of metallogels in next-generation soft technologies, including sensing, energy conversion, wound healing, drug delivery, and emerging applications such as soft electronics and on-skin catalytic or bioactive patches. By mapping current progress and emerging design principles, this review aims to support the rational engineering of metallogels for advanced technological and biomedical applications Full article

The precise management of chronic wounds poses a global medical challenge, owing to their complex and dynamically shifting pathological microenvironment, coupled with their inherent difficulty in healing. Traditional dressings, which lack capabilities for real-time monitoring and active intervention, fall short of meeting modern clinical needs. Composite hydrogels offer a novel solution to this problem. By integrating functional fillers within biocompatible hydrogel matrices, they form intelligent materials capable of sensing key wound parameters. This review systematically outlines the composite systems and material classification of such hydrogels designed for the intelligent monitoring of chronic wounds. It subsequently details the construction of multimodal monitoring systems and their applications across different types of chronic wounds., Finally, future development direction are discussed, aiming to advance the implementation of next generation, personalized intelligent wound management systems. Full article

Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and laser therapy, are frequently hampered by limited drug bioavailability, rapid clearance, and treatment-related complications, primarily due to the eye’s unique anatomical and physiological barriers. Hydrogels, characterized by their three-dimensional network structure, high water content, excellent biocompatibility, and tunable physicochemical properties, have emerged as promising platforms for ophthalmic drug delivery. This review summarizes the classification, fabrication strategies, and essential properties of hydrogels, and highlights recent advances in their application to ocular diseases, including keratitis management, corneal wound repair, intraocular pressure regulation and neuroprotection in glaucoma, sustained drug delivery for AMD and DR, vitreous substitutes for retinal detachment, and therapies for DED. In particular, we highlight recent advances in stimuli-responsive hydrogels that enable spatiotemporally controlled drug release in response to ocular cues such as temperature, pH, redox state, and enzyme activity, thereby enhancing therapeutic precision and efficacy. Furthermore, this review critically evaluates translational aspects, including long-term ocular safety, clinical feasibility, manufacturing scalability, and regulatory challenges, which are often underrepresented in existing reviews. By integrating material science, ocular pathology, and translational considerations, this review aims to provide a comprehensive framework for the rational design of next-generation hydrogel systems and to facilitate their clinical translation in ophthalmic therapy. Full article

Protein-based hydrogels are increasingly recognized as promising biomaterials for advanced drug delivery, owing to their biocompatibility, biodegradability, and ability to recreate extracellular matrix-like environments. By tailoring the protein source, crosslinking strategy, molecular architecture, and functionalization, these hydrogels can be engineered to mimic the mechanical and biological features of native tissues. Protein-derived hydrogels are currently explored across biomedical and pharmaceutical fields, including drug delivery systems, wound healing, tissue engineering, and, notably, cancer therapy. In recent years, growing attention has been directed toward natural protein hydrogels because of their inherent bioactivity and versatile physicochemical properties. This review provides an updated overview of protein-based hydrogel classification, properties, and fabrication methods. It highlights several widely studied natural proteins, such as gelatin, collagen, silk fibroin, soy protein, casein, and whey protein, that can form hydrogels through physical, chemical, or enzymatic crosslinking. These materials offer tunable mechanical behavior, controllable degradation rates, and abundant functional groups that support efficient drug loading and the development of stimuli-responsive platforms. Furthermore, we examine current advances in their application as drug delivery systems, with particular emphasis on cancer treatment. Protein-based hydrogels have demonstrated the ability to protect therapeutic molecules, provide sustained or targeted release, and enhance therapeutic effectiveness. Although critical challenges, such as batch-to-batch variability, sterilization-induced denaturation, and the requirement for comprehensive long-term immunogenicity assessment, must still be addressed to enable successful translation from preclinical studies to clinical application, ongoing advances in the design and functionalization of natural protein hydrogels highlight their promise as next-generation platforms for precision drug delivery. Full article

Substance-based medical devices (SBMDs) are increasingly used in wound care due to their favorable safety profile, physicochemical mechanisms of action, and therapeutic effectiveness. These products often incorporate biopolymers such as hyaluronic acid or chitosan, alone or in combination with antimicrobial agents like silver nanoparticles (AgNPs) or silver sulfadiazine (SSD), offering hydration, tissue protection, and control of microbial burden in both acute and chronic wounds. Despite their widespread clinical use, the regulatory classification of SBMDs under Regulation (EU) 2017/745 (MDR) remains one of the most challenging and debated areas within the current European framework. This review analyzes the scientific and regulatory context of topical SBMDs, with particular emphasis on borderline products that share similarities with medicinal products in terms of formulation, composition, or claimed effects. The discussion focuses on the application of MDR Annex VIII, specifically Rule 21 for substance-based devices and Rule 14 for devices incorporating medicinal substances with ancillary action, together with interpretative guidance provided by MDCG 2022-5 Rev.1 and the Association of the European Self-Care Industry (AESGP) Position Paper. Particular attention is given to the identification of the critical role of the primary mode of action (MoA) as the determining criterion for regulatory qualification, especially for products containing antimicrobial substances. Through selected examples and case analyses, the review highlights inconsistencies in classification across Member States and underscores the need for a more harmonized, evidence-based, and proportionate regulatory approach. Overall, SBMDs challenge traditional regulatory boundaries and call for a framework capable of accommodating complex, multifunctional products while ensuring patient safety and regulatory coherence. Full article