bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–04–26
forty papers selected by
Luca Bolliger, lxBio
  1. Efficacy and pharmacokinetics of a stepwise isolated phage cocktail against carbapenem-resistant Klebsiella pneumoniae in a murine pneumonia model.
  2. A conserved KL2-capsule-related phage-resistant mechanism in carbapenem-resistant Acinetobacter baumannii is surmountable by a rationally selected dual-phage cocktail.
  3. AI-assisted phage formulation delivered via injectable hydrogels for localized control of implant-associated infections.
  4. Rolling out Plaque-2-seq: a single plaque sequencing approach enabling rapid, low-cost sequencing of phages directly from plaques.
  5. Mapping the Research Landscape and Evolutionary Trends of the Oral Microbiome in Periodontitis.
  6. A novel jumbo phage infecting Pseudomonas aeruginosa: genomic insights and phylogenetic classification.
  7. Protein-Based Nutrition for Chronic Wounds: A Clinician's Guide to Patient Selection, Dosing, Monitoring, and Outcomes.
  8. Pseudomonas aeruginosa: associated pathogenesis, epidemiology, resistance mechanisms, host response and emerging treatment strategies.
  9. Treatment of refractory leg ulcer in a patient with lupus undergoing combination therapies.
  10. From Antibiosis to HOCl Antisepsis: Far-Forward Infection Control in Modern Warfare.
  11. [Gut microbiota involved in cancer invasion and metastasis].
  12. pH/ROS-responsive smart hydrogels for infection control and immune microenvironment modulation in chronic wound healing.
  13. Host-pathogen interactions in periodontitis: an integrative interkingdom perspective.
  14. Exploring the Power of Machine Learning in Analysing Protein-Protein Sequences.
  15. Therapeutic Remodeling of the Gut Microbiome as a Strategy to Restore Immune Tolerance in Autoimmunity.
  16. Peri-Implantitis and Periodontitis: Biological Convergence, Contextual Divergence.
  17. Skin Organoids in Diabetic Chronic Wounds: Current Status and Future Perspectives.
  18. The microbiome landscape of oral cancer in young patients.
  19. Comprehensive Management of Diabetic Foot Ulcers: Current Evidence and Practice.
  20. Unmasking pathogen traits for chronic colonization in neurogenic bladder.
  21. Lung transplant in people with cystic fibrosis and nontuberculous mycobacteria infection.
  22. Platelet-rich plasma in the management of diabetic foot ulcers (Review).
  23. Xylazine-Associated Wounds: A Scoping Review of Clinical Presentation and Management.
  24. Mechanistic insights into the role of oral microbiome in the malignant transformation of oral lichen planus to oral squamous cell carcinoma.
  25. The expanding role of artificial intelligence in personalised medicine: from innovation to individualized care.
  26. 'Real time, real change': the role of artificial intelligence in providing real-time language translation services in regional medicine.
  27. From gut dysbiosis to eubiosis: understanding microbiome recovery as an ecological process.
  28. Physics-inspired explainable AI for mechanistic and decision support in drug discovery.
  29. Notch Signalling Pathway in the Pathogenesis of Periodontitis: Research Progress.
  30. Clinical efficacy of Guided Biofilm Therapy in the management of periodontal disease - a systematic review.
  31. Multi-kingdom profiling reveals altered gut phage-bacteria-metabolite interactions in MASLD.
  32. Multidrug-resistant Klebsiella pneumoniae in oncology intensive care units: selected genetic markers and clinical predictors.
  33. Cannabidiol-Loaded Smart Hydrogels for Advanced Wound Healing: Drug Delivery Innovations and Therapeutic Perspectives.
  34. Novel antibacterials targeting multidrug-resistant gram-positive and gram-negative bacteria: an updated review.
  35. What We Can Do in Infectious Keratitis, Except for Conventional Antimicrobial-Based Therapies: Major Narrative Review.
  36. From Anatomy to Innovation: Embedding Patient-Centered Design in Medical Education.
  37. Oral health status in adult and paediatric patients with cystic fibrosis (CF): A systematic review and meta-analysis.
  38. Mapping scientific knowledge on the association between periodontal disease and rheumatoid arthritis: A bibliometric and altmetric analysis of the 100 most-cited articles.
  39. How Transformative Are ROS Responsive Hydrogel Nanoformulations to Treat Refractory Infected Wounds.
  40. Engineered piezoelectric dressings advance cutaneous wound healing.
  1. Int J Antimicrob Agents. 2026 Apr 21. pii: S0924-8579(26)00099-3. [Epub ahead of print] 107810
    Efficacy and pharmacokinetics of a stepwise isolated phage cocktail against carbapenem-resistant Klebsiella pneumoniae in a murine pneumonia model.
    Xin Yin, Huan Luo, Yu Feng, Qingqing Fang, Zhiyong Zong.
      Phage therapy is a potential alternative to conventional antibiotic therapy to combat carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Studies based on pharmacokinetic of phage therapy are scarce, representing a major barrier to clinical translation of phage therapy. Our study provides preclinical evidence supporting the therapeutic potential of a phage cocktail against CRKP pneumonia in mice. The mice were divided into four groups: CRKP infection group (bacteria), phage therapy group (bacteria and phage cocktail), the negative group (phage cocktail), and the blank group (no bacteria and no phage). Samples were collected at 4, 24, 48, and 72 hours after phage cocktail administration. After 4-hour phage therapy, bacterial load in murine lung tissues in the phage therapy group started to decrease. After 72-hour phage therapy, bacterial counts of the lung tissue in the phage therapy group lowered 7.45 log compared to those in the CRKP infection group. Treatment of phage cocktail reduced the level of inflammatory factors (IL-6 and TNF-α) and ameliorated congestion and inflammation in murine lung tissues. The half-lives of phages in the phage therapy were longer than those of the negative group. The phage titers in the phage therapy group were stable within 48 hours. No obvious toxic effect was observed in the negative group. In conclusion, our study supports that phage cocktail could be considered as a potential therapeutic regimen for managing pneumonia due to CRKP.
    Keywords:  carbapenem-resistant Klebsiella pneumoniae (CRKP); murine pneumonia model; phage cocktail; pharmacokinetics
    DOI:  https://doi.org/10.1016/j.ijantimicag.2026.107810
  2. Front Cell Infect Microbiol. 2026 ;16 1790430
    A conserved KL2-capsule-related phage-resistant mechanism in carbapenem-resistant Acinetobacter baumannii is surmountable by a rationally selected dual-phage cocktail.
    Yong Shao, Zhu Gao, Hongyang You, Shaokun Zhang, Jiaqi Zeng, Jiawei Zhao, Chenyan Yuan, Fengqin Miao, Yuqing Shen, Ying Zhang, Ling Liu, Jianqiong Zhang.
       Introduction: As the use of bacteriophages to combat drug-resistant bacteria increases, phage resistance, which may lead to infection recurrence, has gradually gained attention. The intricate mechanisms underlying phage resistance, which are crucial for improving the efficacy of phage therapy, have not yet been fully delineated. This research focuses on uncovering the mechanisms of phage resistance and formulating robust strategy to address infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB).
    Methods: A specific bacterium-phage pair (CRAB strain MRAB11 and lytic phage MRABP9) was employed. Phage-resistant strains were isolated and subjected to whole-genome sequencing, followed by comparative genomics analysis. A novel phage targeting phage-resistant strains, was screened and combined with MRABP9. The efficacy of the phage combination was validated in bacterial liquid growth and in mouse wound CRAB infection model. The antimicrobial spectra of phage MRABP9 and the phage combination were evaluated using multi-center clinical A. baumannii isolates, and the fitness of phage-resistant strains was determined.
    Results: All sequenced phage-MRABP9-resistant strains harbored mutations on KL2 locus under both in vitro and in vivo conditions. A novel phage MRABphi22 targeting phage-resistant strains was introduced and its combination with phage MRABP9 effectively inhibited the growth and phage resistance development of CRAB, demonstrating promising efficacy in mouse wound infection treatment. The fitness of phage-resistant isolates in terms of antibiotic resistance, virulence and growth rate, was diminished, with dual-phage resistant strains bearing higher fitness costs.
    Conclusions: The mechanism underlying the response of MRAB11 to phage MRABP9 invasion exhibits high consistency on KL2 locus and is surmountable by a well-designed dual-phage cocktail. This study offers valuable guidance for future experimental design of clinical phage therapy, and points out potential therapeutic phage candidates for treating CRAB infections.
    Keywords:  Acinetobacter baumannii; bacterial infection; phage cocktail; phage resistance; phage therapy
    DOI:  https://doi.org/10.3389/fcimb.2026.1790430
  3. Bioact Mater. 2026 Sep;63 578-595
    AI-assisted phage formulation delivered via injectable hydrogels for localized control of implant-associated infections.
    Fereshteh Bayat, Martin Stark, Sara Rahmani, Cindy Sun, Arman Khani, Yassaman Ommi, Lei Tian, Fiorelle C Aguilar Lopez, Jeffrey I Weitz, Tohid F Didar, Zeinab Hosseinidoust.
      Bacteriophages are emerging as highly effective antimicrobials for the treatment of persistent bacterial infections, offering precision-targeted action ideal for personalized medicine. Here, we present a scalable phage therapy platform specifically engineered for implant infections. Using an unsupervised machine learning-assisted clustering model, we selected phage combinations for enhanced antibacterial synergy that were delivered using a minimally invasive, shelf-stable composite hydrogel. The hydrogel was composed of laponite nanoclay and carboxymethyl cellulose, delivering a binary Pseudomonas aeruginosa phage cocktail. The phage cocktail-loaded composite nanoclay hydrogel achieved a 5-log bacterial reduction in a biofilm model, while in vivo studies in a murine implant infection model showed 100% survival of treated mice compared to 60% in controls. The composite phage-nanoclay hydrogel also demonstrated a 50% reduction in friction, maintained shelf-life of up to 18 months, and sustained phage release in vivo. Our results demonstrate the power of AI-assisted phage formulation paired with multifunctional biomaterials as a customizable and effective strategy for precision treatment of bacterial infections, advancing the clinical potential of phage therapy.
    Keywords:  AMR; Biofilm disruption; Controlled release; Osteointegration; Phage synergism
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.04.013
  4. Microb Genom. 2026 Apr;12(4):
    Rolling out Plaque-2-seq: a single plaque sequencing approach enabling rapid, low-cost sequencing of phages directly from plaques.
    Slawomir Michniewski, Rebecca Glenny, Andrew Kinsella, Kane Porter, Kayne Wright, Sophie Harrison, Nzubechukwu I Ugokwe, Amani Alrashidi, Srwa J Rashid, Chisomaga Eke, Jack C D Lee, Faizal Patel, Theo Josephs, Arezoo Pedramfar, Max Coleman, Hasanain F Y Al-Dahash, Gibson A Sabuholo, Navodya S Roemer, Hannah Sampson, Gerald N Misol, Branko Rihtman, David J Scanlan, Elspeth Smith, Graham Stafford, Willem van Schaik, Richard J Puxty, Edouard Galyov, Martha R J Clokie, Spyridon Megremis, Andrew Millard.
      Rapid, accurate and scalable sequencing of bacteriophage genomes is critical to advance phage therapy, build phage biobanks and understand phage genomic diversity. Current methods are based on sequencing and assembling complete bacteriophage genomes using short- or long-read technologies. However, current protocols require large DNA input and are cost-prohibitive, which limits their application to phage collections that typically are large and have low biomass. In order to address this, we have developed Plaque-2-seq, a robust and cost-effective workflow for high-throughput phage genome sequencing that will transform the speed and cost of attaining phage genomes. Plaque-2-seq combines low-input transposase-based library preparation, amplification, nanopore sequencing and optimized assembly steps tailored to phage genomes. We applied the method to phages isolated on seven genetically diverse bacterial hosts: Escherichia, Pseudomonas, Synechococcus, Enterococcus, Klebsiella, Serratia and Enterobacter. High-quality genome assemblies were validated using CheckV and benchmarked against previously sequenced phage isolates. Compared to standard Illumina sequencing, Plaque-2-seq offers up to ~5-10-fold savings in sequencing price for individual labs. Furthermore, it substantially decreases the time required to produce a phage genome, once a plaque is obtained. Offering the ability to routinely obtain hundreds of phage genome sequences a week, with minimal hands-on time. Plaque-2-seq enables systematic genomic characterization of phage isolates, facilitating taxonomic classification, for the development of large-scale phage biobanks.
    Keywords:  bacteriophages; genomes; genomics; long-read sequencing; phages; sequencing
    DOI:  https://doi.org/10.1099/mgen.0.001672
  5. APMIS. 2026 Apr;134(4): e70209
    Mapping the Research Landscape and Evolutionary Trends of the Oral Microbiome in Periodontitis.
    Xue Wang, Yihui Ma, Ying Yang, Qingshan Dong.
      The conceptual transition from the "Red Complex" paradigm to the "Ecological Plaque Hypothesis" has fundamentally reshaped the understanding of periodontitis, but a quantitative mapping of this intellectual evolution and its emerging research frontiers remains limited. This study systematically characterized the global research landscape and evolutionary trends of the oral microbiome in periodontitis from 2000 to 2025. English-language articles published between 2000 and 17 November 2025 were retrieved from the Web of Science Core Collection and Scopus databases. After deduplication, bibliometric analyses were performed on 2827 unique publications to evaluate spatiotemporal distributions, collaboration patterns, thematic evolution, and citation bursts. The results revealed exponential growth in publications, particularly after 2020, with the United States and China leading global contributions. Thematic evolution analyses demonstrated a clear shift from single-pathogen-focused research, exemplified by Porphyromonas gingivalis, toward ecological frameworks emphasizing dysbiosis and microbial community structure. Recent citation bursts highlighted growing attention to broader microbial taxa, inflammatory mediators, clinically relevant periodontal indicators, microbiome-based therapeutic strategies, and methodological standardization. Overall, research on the oral microbiome in periodontitis has evolved toward a host-microbiome systems biology framework, with future studies likely to emphasize functional multi-omics integration, AI-assisted diagnostics, and precision interventions targeting oral-systemic health links.
    Keywords:  dysbiosis; host–microbial interactions; oral microbiota; periodontitis
    DOI:  https://doi.org/10.1111/apm.70209
  6. Arch Microbiol. 2026 Apr 24. pii: 357. [Epub ahead of print]208(7):
    A novel jumbo phage infecting Pseudomonas aeruginosa: genomic insights and phylogenetic classification.
    Hüseyin Özgür Özdemirel, Hazal Tahravi, Sibel Kucukyildirim, Ahmet Çağkan İnkaya, Hatice Mergen.
      
    Keywords:  Antibiotic resistance; Bacteriophage therapy; Jumbo phage; Opportunistic pathogen
    DOI:  https://doi.org/10.1007/s00203-026-04916-4
  7. Adv Wound Care (New Rochelle). 2026 Apr 19. 21621918261444178
    Protein-Based Nutrition for Chronic Wounds: A Clinician's Guide to Patient Selection, Dosing, Monitoring, and Outcomes.
    Zilong Tan, Yi Ru, Caiyun Zhang, Xinxin Wu, Qingkai Liu, Bin Li, Qilong Chen.
       SIGNIFICANCE: Chronic wounds remain a major global health burden and often stall despite guideline-based care because of persistent inflammation, oxidative stress, impaired perfusion, and dysregulated extracellular matrix remodeling. Protein-based nutrition is best positioned as an adjunct to, rather than a substitute for, standard wound care.
    RECENT ADVANCES: Human studies, supported by mechanistic rationale, suggest that optimizing total protein intake (commonly ∼1.25 to 1.5 g/kg/day in appropriate patients) and, in selected settings, adding functional components such as arginine, glutamine, and β-hydroxy-β-methylbutyrate (HMB) may improve wound-area reduction and healing trajectories when integrated with standard care. Reported signals vary by etiology, including improved wound-area reduction and Pressure Ulcer Scale for Healing outcomes in pressure injuries, possible benefit in selected high-risk diabetic foot ulcer subgroups, and reduced venous ulcer area when supplementation is paired with consistent compression.
    CRITICAL ISSUES: Evidence remains heterogeneous across wound types and study designs, with inconsistent dosing, duration, endpoints, and patient-selection criteria that limit standardized implementation. Safety and feasibility are especially important in renal risk and diabetes, where renal function and glycemic control require monitoring. Clinical evidence was interpreted with attention to study design and reporting standards, including CONSORT, STROBE, or STARD, as applicable.
    FUTURE DIRECTIONS: This review translates current evidence into a clinician-oriented framework for patient selection, prescribing, monitoring, and treatment adjustment, emphasizing initiation triggers in stalled wounds and trajectory-based reassessment every 2-4 weeks. Future work should prioritize pragmatic, well-controlled trials comparing formulations and dosing windows by wound etiology, together with biomarker-informed stratification to improve personalization, safety, and real-world uptake.
    Keywords:  arginine; chronic wounds; oral nutritional supplements; precision nutrition; protein-based nutrition; wound healing
    DOI:  https://doi.org/10.1177/21621918261444178
  8. Arch Microbiol. 2026 Apr 24. pii: 351. [Epub ahead of print]208(7):
    Pseudomonas aeruginosa: associated pathogenesis, epidemiology, resistance mechanisms, host response and emerging treatment strategies.
    Sheeba Sawant, Safura Shaikh, Timothy C Baldwin, Aikaterini Karakoula, Ayesha Rahman.
      Pseudomonas aeruginosa is recognized as a critical-priority pathogen due to its major role in healthcare-associated infections (HAIs) and the rapid global rise of multidrug resistance. It is responsible for approximately 7.1-7.3% of HAIs worldwide and up to 23% of intensive care unit infections, specifically ventilator-associated pneumonia, where mortality can reach 32-42.8%. In chronic lung diseases, especially cystic fibrosis, P. aeruginosa commonly becomes the dominant pathogen in adulthood and contributes to progressive lung function decline. A major factor supporting long-term survival is biofilm formation, which can increase antimicrobial tolerance by up to 1000-fold compared with free-living bacteria. Virulence is further regulated through coordinated production of phenazines, rhamnolipids, exopolysaccharides, and quorum sensing signalling systems. The toxin pyocyanin, produced by 90-95% of clinical isolates, damages host tissues by disrupting cellular respiration, impairing ciliary activity, disturbing calcium balance, and promoting neutrophil apoptosis. During chronic infection, host defence mechanisms, including epithelial barriers, mucociliary clearance (~90% removal of inhaled particles), antimicrobial peptides, and immune cell responses, become less effective, while biofilms promote persistent inflammation and poor bacterial clearance. Increasing multidrug and carbapenem resistance (up to 47.6% in Europe and 32.8% in Asia) is driving interest in alternative therapies, including anti virulence agents, biofilm-disrupting enzymes, nanoparticles, bacteriophage therapy, and host-directed approaches targeting excessive inflammatory responses.
    Keywords:   Pseudomonas aeruginosa; Alternative therapies; Antibiotic resistance; Biofilm; Immune response; Nosocomial; Pyocyanin; Quorum sensing; Virulence
    DOI:  https://doi.org/10.1007/s00203-026-04839-0
  9. Wounds. 2026 Feb;38(2): 16-19
    Treatment of refractory leg ulcer in a patient with lupus undergoing combination therapies.
    Chi Young Bang, Seung Ho Lee, Kun Yong Sung.
       BACKGROUND: Systemic lupus erythematosus can present with refractory chronic leg ulcers, often linked to antiphospholipid syndrome or vasculopathy. Standard immunosuppressive therapy may be unsuccessful in such cases, necessitating alternative approaches such as anticoagulation and advanced wound care.
    CASE REPORT: This report presents the case of a 46-year-old male with systemic lupus erythematosus who developed a persistent leg ulcer on the right lateral ankle that was unresponsive to immunosuppressive treatment of more than 6 months' duration. A short-term multimodal therapeutic approach incorporating anticoagulation, negative pressure wound therapy, and cultured epidermal homograft successfully induced robust granulation and marked epithelialization with 1 week of hospitalization, a much shorter period than the previously reported 2 months needed for full resolution with anticoagulation alone. Although in the present case complete epithelial closure was not achieved during the brief inpatient period, the wound showed near-total epithelialization with continued outpatient care, indicating rapid and stable wound recovery.
    CONCLUSION: This case demonstrates that adjunctive use of negative pressure wound therapy and cultured epidermal homograft appears to shorten the healing process compared with anticoagulation therapy alone.
    Keywords:  chronic leg ulcer; cultured epidermal homograft; enoxaparin; negative pressure wound therapy; systemic lupus erythematosus; vasculopathy; wound healing
    DOI:  https://doi.org/10.25270/wnds/25025
  10. J Spec Oper Med. 2026 Apr 23. pii: J.Spec.Oper.Med.2026.KPUM-MM54. [Epub ahead of print]
    From Antibiosis to HOCl Antisepsis: Far-Forward Infection Control in Modern Warfare.
    Eric D Rasmussen, Vasyl Makarov.
      Modern military medicine continues to rely heavily on anti-biotic-based infection treatment, even as antimicrobial resistance, delayed evacuation, and contested logistics erode its effectiveness. A renewed emphasis on antisepsis-safe, stable, potent, broad-spectrum, and field-ready-now offers a practical alternative for far-forward field care and delayed evacuation. Hypochlorous acid (HOCl), a natural antimicrobial compound made by human neutrophils, has regained attention for its effectiveness and safety, making HOCl antisepsis the possible first step in far-forward infection prevention. Advances in electrochemistry now permit local high-volume production of pure, physiologically compatible and noncytotoxic HOCl with a rigorously-tested efficacy and safety profile and a 2-year shelf life. Laboratory, clinical, and humanitarian field data on its application to wounds consistently show rapid microbial reduction and biofilm disruption, leading to measurably enhanced wound healing. For those providing care in resource-limited settings, the use of HOCl demonstrates how infection prevention can move beyond pathogen-specific therapy toward safe and effective antisepsis. This paper outlines the rationale, evidence, and operational considerations supporting a proposed transition. It also argues that adopting point-of-injury wound intervention with HOCl might provide a highly effective, easy to use, and tissue-safe antiseptic for Individual First Aid Kits (IFAKs) and Special Operations medics. It concludes that lessons from the war in Ukraine should inform new research evaluating changes in TCCC protocols.
    Keywords:  HOCl; Tactical Combat Casualty Care; Ukraine; antimicrobial resistance; antisepsis; hypochlorous acid; infection control; trauma; wound management
    DOI:  https://doi.org/10.55460/J.Spec.Oper.Med.2026.KPUM-MM54
  11. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Dec 28. pii: 1672-7347(2025)12-2186-15. [Epub ahead of print]50(12): 2186-2200
    [Gut microbiota involved in cancer invasion and metastasis].
    Siqing Huang, Qin Yang, Wen Zhou.
      The gut microbiota, as the "second genome" of the human body, plays a crucial role in maintaining the host's homeostasis and regulating the disease process. The latest research indicates that intestinal microecological imbalance is an important cause that triggers and accelerates tumor metastasis. The gut microbiota mainly promotes tumor invasion and metastasis through the following 2 mechanisms: 1) Contact-dependent mechanism, specific pathogenic bacteria directly adhere and invade tumor cells through surface proteins, inducing epithelial-mesenchymal transition and cytoskeleton remodeling; 2) non-contact-dependent mechanism, metabolites derived from the microbiota act on distant organs through the bloodstream, activating signaling pathways to construct pre-metastatic ecological niches and inducing systemic immunosuppression. Precise intervention strategies for the gut microbiota include supplementing specific probiotics with anti-cancer potential, selective antibiotics or phage therapy against specific pathogenic bacteria, fecal microbiota transplantation and microbial vaccines. Although preliminary studies have shown promising results, the high heterogeneity of the microbiota, the bidirectional action of metabolites, and the safety of long-term colonization remain bottlenecks for clinical translation. In the future, it is necessary to further clarify the key transfer-promoting microbiota and their characteristic metabolic and signaling mechanisms, promote the development of individualized and precise microbiota intervention strategies, and strengthen clinical translation research, in order to ultimately achieve the goal of effectively preventing and treating tumor metastasis by regulating the gut microbiota.
    Keywords:  cancer; gut microbiota; intervention; invasion; metabolites; metastasis
    DOI:  https://doi.org/10.11817/j.issn.1672-7347.2025.250361
  12. Front Cell Dev Biol. 2026 ;14 1826583
    pH/ROS-responsive smart hydrogels for infection control and immune microenvironment modulation in chronic wound healing.
    Rui Zhang, Suk Fei Tan, Wenqin Zhang, Ye Wang, Junxue Wu, Chao Zhang.
      Chronic wounds are characterized by persistent infection, excessive oxidative stress, and dysregulated inflammation, which together hinder tissue repair and promote non-healing states. In this context, pH/ROS-responsive hydrogels have emerged as promising smart wound-dressing platforms because they can exploit local acidic and oxidative cues for site-specific structural change, controlled cargo release, and microenvironment-adaptive therapy. This review summarizes the pathological basis for pH/ROS-responsive intervention and discusses recent advances in hydrogel design for infection control, ROS scavenging, and immune microenvironment modulation. We further highlight key translational challenges, including manufacturing complexity, degradation-product safety, storage stability, and the limitations of current preclinical models. Overall, pH/ROS-responsive hydrogels represent a promising strategy for chronic wound management, but future progress will depend on achieving a better balance between multifunctional performance and translational practicality.
    Keywords:  ROS-responsive; chronic wound; diabetic wound; immune microenvironment; infection control; macrophage polarization; pH-responsive; smart hydrogel
    DOI:  https://doi.org/10.3389/fcell.2026.1826583
  13. Front Immunol. 2026 ;17 1797726
    Host-pathogen interactions in periodontitis: an integrative interkingdom perspective.
    Lina Janeth Suarez, Paula K Vargas-Sanchez, Nikola Angelov, Eleftherios Mylonakis, Roger M Arce.
      Periodontitis is an infectious, inflammatory, non-communicable disease characterized by tissue destruction driven by host responses to dysbiotic shifts in oral microbial communities. The subgingival microbiome constitutes a complex ecosystem in which bacteria, fungi, viruses, and archaea interact via interkingdom communication to modulate the inflammatory response through molecular mechanisms that remain largely unknown. This narrative review aims to understand how functional imbalances within the microbiome alter the microenvironment and promote uncontrolled inflammation responsible for periodontal tissue damage, with implications for systemic disease. The search strategy was conducted according to the PRISM-S extension, to include studies evaluating interkingdom host-pathogen interactions at the gingiva interphase leading to microbial and immune dysbiosis. The discovery of fungi acting as opportunistic pathogens highlights their role in enhancing biofilm virulence and exacerbating host responses, contributing to the total inflammatory burden. Similarly, viruses and archaea influence bacterial metabolism through mechanisms including lysis, nutrient recycling, horizontal gene transfer, and interspecies hydrogen transfer. This interkingdom crosstalk disrupts symbiosis, facilitating enhanced biofilm formation, increased production of virulence factors, and antibiotic resistance. A better understanding of the interkingdom perspective necessitates a comprehensive polymicrobial approach to diagnosis and treatment that extends beyond simply controlling bacteria to include the modulation of interkingdom communication systems. Developing new therapeutic alternatives that address these complex interactions is essential for improving outcomes achieved with mechanical therapy and managing the interrelationships between periodontitis and other systemic diseases.
    Keywords:  biofilms; dysbiosis; host-pathogen interactions; mouth microbiota; periodontitis
    DOI:  https://doi.org/10.3389/fimmu.2026.1797726
  14. IET Syst Biol. 2026 Jan-Dec;20(1):20(1): e70066
    Exploring the Power of Machine Learning in Analysing Protein-Protein Sequences.
    Anindya Nag, Riya Sil, Md Mehedi Hassan, Tamanna Haque Ritu, Biva Das, Nilanjana Roy, Anurag Sinha, Dron Guin, Nishchal Maurya.
      Proteins are fundamental biological macromolecules responsible for regulating nearly all cellular processes, and their functions are largely determined by the underlying amino acid sequences. Understanding the relationship between protein sequences and their structural and functional properties remains a major challenge in molecular biology. Although experimental techniques provide accurate insights, they are often time-consuming and expensive, which has led to increasing reliance on computational approaches for protein sequence analysis and structure prediction. Numerous techniques-including homology modelling, machine learning, deep learning, natural language processing and other artificial intelligence methods-have been developed for analysing protein sequences and predicting protein-protein interactions. However, the rapidly growing number of computational methods makes it difficult for researchers to systematically evaluate and select suitable approaches for specific biological applications. This study presents a comprehensive review of recent computational techniques for protein sequence analysis, focusing on machine learning- and deep learning-based frameworks used for predicting protein structure and interactions. This review systematically categorises existing approaches based on their methodological foundations, datasets and performance characteristics and provides a comparative discussion of their advantages and limitations. Furthermore, this study highlights current research gaps, challenges in large-scale protein analysis and emerging trends in AI-driven protein modelling. The findings of this review provide a structured reference for researchers and practitioners, facilitating the selection of appropriate computational techniques and supporting future advancements in protein sequence analysis, disease research and drug discovery.
    Keywords:  biomedical engineering; data mining; feature extraction; feature selection; principal component analysis; proteins; statistical analysis
    DOI:  https://doi.org/10.1049/syb2.70066
  15. Microbiologyopen. 2026 Apr;15(2): e70294
    Therapeutic Remodeling of the Gut Microbiome as a Strategy to Restore Immune Tolerance in Autoimmunity.
    Behshad Boroumand, Amirhossein Jaberi, Ghazal Zamani, Ehsan Zandi, Farshad Zare, Milad Vahedinezhad, Elham Abdollahi, Sepideh KarkonShayan, Sasan GhazanfarAhari, Mustafa Sattar.
      Autoimmune diseases happen when the immune system, which is supposed to defend the body from infections and other harmful things, starts to attack the body's own cells by mistake. In the last few years, they seem to be getting more public, and the reasons are quite complicated. It is usually not just one factor, but a mix of genes and environmental influences, such as diet, infections, or even stress. The gut microbiome, the vast community of bacteria and other tiny organisms living in our intestines, plays an important role in shaping how the immune system behaves. When this gut microbiota becomes unstable (a state called dysbiosis), it can be associated with the onset or worsening of various autoimmune diseases. In this review, we discuss the close relationship between the gut microbiome and autoimmune disorders and focus on how the microbiome can affect immune activation, immune tolerance, and inflammation at the molecular level. The general idea is that, if we understand these interactions better, we might be able in the future to design new ways to manage autoimmune diseases earlier and maybe in a more personalized way. In the end, the review suggests that if we understand better how the microbiome is involved in autoimmune diseases, it might be possible in the future to design more personalized therapies that change gut bacteria in a smart way and hopefully improve patient outcomes.
    Keywords:  autoimmune diseases; dysbiosis; gut microbiome; immune modulation; probiotics
    DOI:  https://doi.org/10.1002/mbo3.70294
  16. J Periodontal Res. 2026 Apr 20.
    Peri-Implantitis and Periodontitis: Biological Convergence, Contextual Divergence.
    Pablo Galindo-Moreno, Pablo Galindo-Fernandez, Allinson Olaechea, Francisco O'Valle, Abdusalam E Alrmali, Hom-Lay Wang, Miguel Padial-Molina.
      Periodontitis and peri-implantitis are chronic inflammatory conditions of microbial origin that affect the supporting tissues of teeth and dental implants, respectively. Although they share comparable clinical features and several histopathological characteristics, they have traditionally been classified as distinct diseases, largely because they arise in different anatomical and clinical contexts. This narrative, question-driven review evaluates clinical, microbiological, histological, and molecular evidence to address whether observed similarities and differences between the two conditions reflect truly distinct diseases, context-dependent variations of a shared inflammatory spectrum, or artifacts of study design and nomenclature. While peri-implantitis is often described as progressing more rapidly or exhibiting more pronounced inflammatory infiltrates, the underlying reasons for these patterns remain under investigation. To date, no microbial species or host-response pathway has been conclusively identified as exclusive to either disease, although most available data derive from heterogeneous, often underpowered studies with limited head-to-head comparisons. Structural and anatomical distinctions, such as the absence of a periodontal ligament around implants and differences in connective tissue organization, may influence disease behavior, yet their precise role in determining divergent outcomes is still debated. Microbial variability also appears to reflect host-specific and site-specific factors more than strict disease categorization, and molecular and transcriptomic studies generally reveal overlapping patterns of immune activation and gene expression, although some analyses suggest potential quantitative or contextual differences, whose interpretation is constrained by small sample sizes and indirect comparisons. Overall, current evidence supports a substantial convergence in pathogenic pathways, superimposed on site-specific and host-specific modulators, rather than clearly segregated disease-specific mechanisms. Given the limited and inconsistent literature, particularly for advanced omics and tissue-based studies, any categorical distinction between periodontitis and peri-implantitis as separate entities remains premature. Future research should prioritize adequately powered, longitudinal, within-subject comparisons and high-resolution approaches, including spatial transcriptomics and integrated immune-molecular profiling, to refine diagnostic concepts and inform individualized therapeutic strategies.
    Keywords:  cytokines; inflammation; microbiota; periodontitis; peri‐implantitis
    DOI:  https://doi.org/10.1111/jre.70109
  17. Diabetes Metab Syndr Obes. 2026 ;19 598026
    Skin Organoids in Diabetic Chronic Wounds: Current Status and Future Perspectives.
    Zhiyao Wang, Minjie Hou, Jie Pei, Fei Gao, Zhi Li.
      Diabetes is one of the most prevalent chronic metabolic diseases worldwide, and its incidence continues to rise. Diabetes-related complications have become a major public health concern, with diabetic chronic wounds-particularly diabetic foot ulcers-representing one of the most challenging and clinically significant manifestations. These non-healing wounds often require prolonged recovery, severely impair patients' quality of life, and impose substantial economic and psychological burdens on healthcare systems and families. Conventional therapeutic approaches are limited by insufficient reparative capacity, scarcity of functional tissue sources, and the inability to achieve durable structural and functional restoration, frequently resulting in suboptimal outcomes. Recent advances in stem cell engineering and three-dimensional tissue technologies have enabled the development of organoids-emerging biomimetic regenerative constructs-allowing their increasing application in tissue repair, including diabetic ulcers. This review provides an integrated summary of the major barriers to diabetic wound healing, the regenerative mechanisms of skin organoids, and recent progress in this field. Unlike previous reviews that address organoids or wound healing separately, this work specifically focuses on diabetic chronic wounds while emphasizing engineering strategies, regenerative potential, and translational considerations. We further analyze the key challenges that hinder clinical translation, including model consistency, vascularization capacity, long-term functional stability, immune compatibility, potential tumorigenicity, and interactions with the local microenvironment. Collectively, this work aims to provide a structured framework and future research directions for the application of skin organoids in diabetic chronic wound repair, supporting their responsible transition from experimental research toward clinical practice.
    Keywords:  diabetes; diabetic foot ulcer; regenerative medicine; skin organoids; tissue engineering; wound healing
    DOI:  https://doi.org/10.2147/DMSO.S598026
  18. JNCI Cancer Spectr. 2026 Apr 21. pii: pkag022. [Epub ahead of print]
    The microbiome landscape of oral cancer in young patients.
    Laveniya Satgunaseelan, Dario Strbenac, Carsten Palme, Tsu-Hui Hubert Low, James Wykes, Tim Manzie, Jonathan R Clark, Jean Y H Yang, Ruta Gupta.
       BACKGROUND: The incidence of oral squamous cell carcinoma (OSCC) is rising in patients under the age of 50, without smoking or alcohol abuse. Viruses are not a causative factor of OSCC in younger patients. The oral microbiome has not been evaluated in this unique patient cohort for a potential bacterial aetiology.
    METHODS: We report the bacterial diversity and composition of the largest cohort of OSCC patients with whole genome sequencing (WGS) (n = 72) and compare it with oral mucosa from healthy controls (n = 10) using the Strengthening the Organization and Reporting of Microbiome Studies guidelines.
    RESULTS: The microbial diversity between tumour, normal mucosa from cancer patients and healthy control mucosa is significantly different, with specific species (Streptococcus mitis, Haemophilus haemolyticus and Cutibacterium acnes) reduced in normal mucosa of cancer patients as compared to healthy controls (adjusted p < 0.05). The microbial diversity is significantly higher in younger patients as compared to older patients (p < 0.001), with a reduced abundance of anaerobes in older patients (Aggregatibacter segnis, Gemella morbillorum, Peptostreptococcus stomatis, Filifactor alocis and Porphyromonas endodontalis; adjusted p < 0.05).
    CONCLUSION: The OSCC tissue of younger patients is significantly more polymicrobial, and their OSCC microbiomes harbour more anaerobic bacteria as compared to older patients. This compositional difference builds the hypothesis that the oral microbiome of younger OSCC patients may have a more hypoxic, immunosuppressive tumour microenvironment with its associated implications for treatment resistance and a potential link to baseline poor dentition.
    DOI:  https://doi.org/10.1093/jncics/pkag022
  19. J Diabetes. 2026 Apr;18(4): e70221
    Comprehensive Management of Diabetic Foot Ulcers: Current Evidence and Practice.
    Ji Min Kim, Seon Mee Kang, Jung Hwa Jung, Ki Chun Kim, Sanghyun Ahn, Chong Hwa Kim, Tae Sun Park, Ie Byung Park.
      Diabetic foot ulcers (DFUs) represent one of the most severe and resource-demanding complications of diabetes mellitus, significantly contributing to morbidity through infections, lower-limb amputations, reduced quality of life, and elevated healthcare expenditures. The etiology of DFUs involves a multifaceted interplay among diabetic neuropathy, peripheral arterial disease, biomechanical abnormalities, and compromised tissue repair mechanisms. Despite advancements in diabetic care, DFUs continue to pose a substantial global health burden characterized by high recurrence rates and suboptimal long-term outcomes, particularly evident in regions such as China, where recurrence rates within 1 year exceed 30% among previously healed patients. Effective DFU management requires an integrated, multidisciplinary approach beginning with early risk stratification and accurate diagnosis, followed by targeted antimicrobial therapy, meticulous wound management, appropriate mechanical offloading, and comprehensive vascular assessment and intervention. This review synthesizes contemporary evidence and current clinical guidelines concerning DFU epidemiology, diagnostic criteria, and therapeutic strategies, underscoring the critical role of interdisciplinary coordinated care to enhance clinical outcomes and mitigate associated complications.
    Keywords:  amputation; diabetic foot; diabetic neuropathy; foot ulcer; peripheral arterial disease
    DOI:  https://doi.org/10.1111/1753-0407.70221
  20. Cell Rep. 2026 Apr 22. pii: S2211-1247(26)00380-3. [Epub ahead of print]45(5): 117302
    Unmasking pathogen traits for chronic colonization in neurogenic bladder.
    Seth A Reasoner, Brendan T Frainey, Owen F Hale, Alexandra Borden, M Kyle Graham, Elise Turner, Lucas R Brenes, Carl B W Soderstrom, Hamilton Green, Jonathan E Schmitz, Michael T Laub, Maryellen S Kelly, Douglass B Clayton, Maria Hadjifrangiskou.
      Individuals with neurogenic bladder are susceptible to chronic bacterial colonization and urinary tract infections. Neurogenic bladder arises from conditions including spinal cord injuries and spina bifida. We established a longitudinal cohort of 77 children and young adults with spina bifida. Using enhanced urine culture, 16S rRNA sequencing, and whole-genome sequencing of bacterial isolates, we characterized the urine microbiota. We also retrieved prior bacterial isolates from Vanderbilt's MicroVU biobank, enabling 5-year evolutionary comparisons within subjects. Urine samples showed high abundance of pathogens, including E. coli and Klebsiella. Across time points, subjects exhibited either rapid cycling of strains, often after antibiotics, or persistence of a single strain. Neither pattern consistently correlated with increased antibiotic resistance. Instead, mutations in cell envelope genes mediated immune evasion and altered phage susceptibility, highlighting fitness trade-offs induced by niche adaptation to the bladder. This cohort enables the identification of bacterial adaptation mechanisms.
    Keywords:  CP: microbiology; bacterial evolution; spina bifida; urinary microbiome; urinary tract infection; urobiome
    DOI:  https://doi.org/10.1016/j.celrep.2026.117302
  21. Cochrane Database Syst Rev. 2026 Apr 21. 4 CD016200
    Lung transplant in people with cystic fibrosis and nontuberculous mycobacteria infection.
    Cochrane Cystic Fibrosis
       RATIONALE: Cystic fibrosis (CF) is an inherited multi-organ disorder. People with CF (pwCF) experience recurrent and chronic lung infections and a progressive loss of lung function. PwCF with poor and rapidly declining lung function may be considered for lung transplantation (LTx), which may improve their quality of life and survival. Nontuberculous mycobacteria (NTM) can cause pulmonary disease in pwCF, and NTM infection is a poor prognostic factor in LTx. Guidelines recommend NTM infection should not automatically preclude LTx. It is important to evaluate the evidence base for LTx in pwCF and NTM pulmonary disease.
    OBJECTIVES: To evaluate clinical outcomes in pwCF and with NTM infection (NTM infection alone or with NTM pulmonary disease) who undergo LTx by comparing: 1. pwCF with current NTM lung infection who undergo LTx versus those with NTM infection who do not undergo LTX; 2. pwCF with current NTM lung infection who undergo LTx versus those without NTM undergoing LTx.
    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, CENTRAL, MEDLINE, Embase, and PubMed as well as two ongoing trials registries. We checked references. The latest search date was 17 February 2026.
    ELIGIBILITY CRITERIA: We considered non-randomised studies of pwCF (any age) with or without NTM lung infection or disease being considered for LTx as well as studies of pwCF and NTM who either did or did not undergo LTx.
    OUTCOMES: Our critical outcomes were mortality, disseminated NTM infection post-LTx, time to chronic lung allograft dysfunction (CLAD), and quality of life at any time points reported. We additionally planned to report lung function, hospitalisations for pulmonary exacerbations, and nutritional parameters in the review.
    RISK OF BIAS: We assessed the risk of bias in three studies using ROBINS-I and in one study using the Joanna Briggs Institute checklist for case series.
    SYNTHESIS METHODS: We could only report results narratively. We used GRADE to assess the certainty of the evidence.
    INCLUDED STUDIES: We included four single-centre retrospective studies (388 adults). Sample sizes ranged from nine to 177 participants. Mycobacteria abscessus was the most common NTM species identified, and all studies reported infection with other pathogens. All studies compared pwCF and NTM infection to pwCF without NTM infection, all undergoing LTx. Each study reported mortality and disseminated NTM infection post-LTx; two studies recorded CLAD. No study reported quality of life, specific lung function measures (although one study commented briefly on lung function in general), hospitalisations for pulmonary exacerbations, or nutritional parameters.
    SYNTHESIS OF RESULTS: We analysed all NTM infections together for practical reasons and were not able to undertake a planned subgroup analysis by subspecies, but acknowledge that the prognosis and clinical trajectory of pwCF infected with different NTM may not be similar. We downgraded the certainty of the evidence due to non-randomised study design and serious risk of bias across all studies. We assessed all identified evidence as of very low certainty, such that lung transplant may have little to no effect on any of the outcomes listed below, but the evidence is very uncertain. Mortality Two studies (18 participants with NTM) reported similar survival data between NTM-positive LTx recipients and matched controls without NTM. Another study (9 participants) reported that two of five participants NTM-positive at LTx died within a few months post-LTx, whilst one of four NTM-negative participants died three years post-LTx due to chronic rejection. One study (177 participants) found that pwCF who had positive NTM cultures pre-LTx had a longer median survival duration than those who had negative cultures. This study additionally reported on survival of participants with post-LTx NTM infection, finding that the five participants who had post-LTx NTM disease had a longer mean survival duration than the 141 participants without post-LTx NTM disease. Disseminated NTM infection post-LTx In the largest study, of the 18 pwCF with NTM at the time of LTx, seven had at least one positive NTM culture, and four developed NTM disease post-LTx. Conversely, 79 of the 89 pwCF without NTM remained so post-LTx; 10 participants recorded a positive NTM culture, but none developed NTM disease. For the 39 participants without a baseline NTM culture, three participants recorded positive NTM cultures post-LTx, and one developed NTM disease. Of the remaining small studies, one reported that NTM was isolated in four of 13 participants at LTx and in three of these post-LTx. A second study reported that one out of five pwCF had NTM infection post-LTx (all were positive at LTx). The third study reported that five out of nine participants had NTM disease at LTx, and two of these five remained NTM-positive post-LTx. CLAD Two studies assessed CLAD. One study reported that none of the five NTM-positive LTx recipients developed CLAD, stating that the risk of CLAD appeared to be similar between the NTM and the comparator group. The second study stated that three out of nine LTx recipients with NTM disease developed chronic rejection or graft dysfunction.
    AUTHORS' CONCLUSIONS: There are no randomised trials to guide clinicians and patients or their families when making decisions regarding LTx in pwCF with NTM. The available data come from observational studies and registry data, often with few people with NTM reported. It has not been possible to pool the available data in meta-analysis, and we are very uncertain of the effect of NTM on pwCF undergoing LTx on the risk of developing NTM disease post-LTx, survival after LTx, and the development of CLAD. The studies were small and at times contradictory. In the era of highly effective modulator treatments, as some centres do not offer LTx to people with a history of NTM, there is an urgent need for more data to guide decision-making.
    FUNDING: This review is part of a suite of reviews on NTM funded jointly by the CF Foundation and the CF Trust.
    REGISTRATION: Protocol registration (2024): www.crd.york.ac.uk/PROSPERO/view/562682.
    DOI:  https://doi.org/10.1002/14651858.CD016200
  22. Biomed Rep. 2026 Jun;24(6): 69
    Platelet-rich plasma in the management of diabetic foot ulcers (Review).
    Andrei-Alexandru Tomac, Cătălin Mircea Coșarcă, Cristian Trâmbițaș, Dorin Constantin Dorobanțu, Mihaela Pertea, Raluca Tilinca, Cosmin Carasca, Gergo Raduly, Maria Gabriela Rezmuves, Mariana Cornelia Tilinca.
      Diabetes mellitus represents a major global health concern, frequently complicated by chronic, non-healing wounds such as diabetic foot ulcers (DFUs). These ulcers are a leading cause of morbidity, impaired quality of life and limb amputation among individuals with diabetes. The impaired healing capacity observed in DFUs results from persistent inflammation, ischemia and a deficiency of local growth factors, which together hinder effective tissue regeneration. Platelet-rich plasma (PRP), an autologous or allogeneic concentrate of platelets, fibrin, cytokines and leukocytes, has been proposed as a biologically active adjunct capable of accelerating tissue regeneration. The present study performed a narrative review of clinical trials and comparative studies assessing PRP therapy compared with the standard of care (SOC) in the treatment of DFUs. Across the reviewed literature, PRP demonstrated higher complete healing rates and a shorter time-to-closure compared with the SOC. In addition, a reduction in infection rates, pain intensity and ulcer recurrence was consistently reported, with minimal adverse effects. Both autologous and allogeneic PRP preparations were effective, and no major difference was observed between topical application and perilesional injection. In conclusion, PRP therapy represents a safe and promising option for enhancing wound healing in patients with DFUs. However, the lack of standardized preparation protocols and heterogeneous study methodologies underscores the need for well-designed, multicenter randomized trials to confirm these findings and to establish optimal treatment parameters.
    Keywords:  diabetes; diabetic foot ulcer; platelet-rich-plasma; platelets; standard of care
    DOI:  https://doi.org/10.3892/br.2026.2142
  23. Adv Skin Wound Care. 2026 May 01. 39(4): E185-E193
    Xylazine-Associated Wounds: A Scoping Review of Clinical Presentation and Management.
    John R Vaile, William C Connolly, Alexander P Zavitsanos, Emily L Isch, Jillian H Zavodnick, Sami Tannouri, Heather A McMahon.
       OBJECTIVE: Xylazine-adulterated opioids have led to an increase in xylazine-associated wounds (XAWs) among people who use drugs. This scoping review synthesizes current information on the clinical presentation and management of XAWs.
    DATA SOURCES: Investigators searched PubMed and Scopus for English-language articles on the clinical presentation or management of XAWs.
    STUDY SELECTION: Exclusion criteria included non-English articles, wounds not associated with xylazine, lack of clinical presentation or management information, brief communications, and review articles. Of 2711 articles screened, 10 met the inclusion criteria.
    DATA EXTRACTION: Extracted data included patient characteristics, clinical presentation, and medical or surgical management.
    DATA SYNTHESIS: Among 22 patients, wounds initially presented at and/or away from injection sites as dark blisters with irregular borders, then evolved into dry, adherent eschar; some wounds progressed to deeper ulcers with intact skin islands. Eight of the 10 studies reported at least 1 case of superinfection, with the most common being periwound cellulitis or abscess. Infection-control measures included debridement, wound-bed preparation, moisture control with appropriate dressings, cultures, consistent documentation of wound changes, and hand hygiene. Nonhealing wounds required further surgical interventions such as debridement (n=4), upper extremity amputation (n=3), or microvascular flap coverage (n=1). Only 2 patients fully recovered; the remainder were lost to follow-up.
    CONCLUSIONS: Xylazine-associated wounds necessitate multidisciplinary care strategies that prioritize wound care, harm reduction, and comprehensive withdrawal management to address both the physical and psychosocial needs of people who use drugs.
    Keywords:  necrosis; substance use disorder; tranquilizer; wound care; xylazine
    DOI:  https://doi.org/10.1097/ASW.0000000000000436
  24. Front Oncol. 2026 ;16 1694005
    Mechanistic insights into the role of oral microbiome in the malignant transformation of oral lichen planus to oral squamous cell carcinoma.
    Yue Wu, Yaoqi Chen, Jingjing Mao, Kelong Li, Qiao He, Zhongwei Zhou.
      Oral Lichen Planus (OLP) is a common oral potentially malignant disorder, and its transformation into Oral Squamous Cell Carcinoma (OSCC) has become a research focus. In recent years, increasing attention has been paid to the role of the oral microbiome in tumor initiation and progression. Studies have shown that dysbiosis of the oral microbiome may contribute to and accelerate the malignant transformation of OLP to OSCC through multiple mechanisms, including the induction of inflammatory responses, disruption of immune regulation, promotion of oxidative stress, and epithelial-mesenchymal transition (EMT). This review summarizes recent advances in research on the characteristic changes in the oral microbiome and associated molecular mechanisms during the malignant transformation of OLP, aiming to provide a theoretical basis and scientific support for early warning and microecological-targeted interventions in OLP malignancy.
    Keywords:  epithelial-mesenchymal transition; malignant transformation; oral lichen planus; oral microbiome; oral squamous cell carcinoma
    DOI:  https://doi.org/10.3389/fonc.2026.1694005
  25. Front Med (Lausanne). 2026 ;13 1795879
    The expanding role of artificial intelligence in personalised medicine: from innovation to individualized care.
    Abrar Ali, Mohd Adnan Kausar, Sadaf Anwar, Farida Habib Khan, Halima Mustafa Elagib, Mona M Shahien, Fahad M Alshabrmi.
      Artificial intelligence (AI) has become a transformative force in precision medicine, enabling unprecedented personalization of healthcare therapies via sophisticated computational analysis of complex biomedical data. This review examines the evolving landscape of AI applications in precision medicine, highlighting both established technologies and emerging advances that are reshaping clinical practice. Current applications demonstrate the ability of AI to enhance diagnostic precision, refine treatment decisions, accelerate drug development, and improve patient outcomes across multiple disease domains. Despite significant progress, challenges related to data standardization, algorithmic bias, legal frameworks, and equi7 access remain key barriers to broader implementation. As technical capabilities advance and integration with healthcare systems deepens, AI-driven precision medicine is poised to profoundly transform therapeutic strategies via enhanced personalization based on individual biological, environmental, and clinical variables.
    Keywords:  artificial intelligence; deep learning; drug discovery; genomics; machine learning; precision medicine
    DOI:  https://doi.org/10.3389/fmed.2026.1795879
  26. Intern Med J. 2026 Apr 22.
    'Real time, real change': the role of artificial intelligence in providing real-time language translation services in regional medicine.
    Oliver Leslie, Alasdair Leslie, Brandon Stretton, Domenico Barbaro, Daniel Zweck, Josh Andrews.
      Artificial intelligence (AI) is rapidly evolving worldwide, enabling greater flexibility and applicability to the field of language translation within healthcare. Australia is currently one of the most culturally and linguistically diverse countries in the world, creating a growing pressure on translators to ensure there is equitable and culturally safe access to healthcare services. Emerging research supports the use of AI as an adjunct to the current translator framework in being able to support low-risk communication tasks, such as appointment coordination or simple instructions, but it should be avoided in high-stakes contexts including informed consent or complex management discussions. Importantly, human oversight is needed to ensure clinical accuracy and patient safety during all translations.
    Keywords:  Artificial Intelligence; Language Translation; Machine Learning; Regional Medicine
    DOI:  https://doi.org/10.1111/imj.70446
  27. Gut Microbes. 2026 Dec 31. 18(1): 2649448
    From gut dysbiosis to eubiosis: understanding microbiome recovery as an ecological process.
    Megan S Kennedy, Eugene B Chang.
      Predicting and promoting gut microbiome recovery following perturbations such as antibiotic treatment, dietary shifts, or inflammation remain major challenges in microbiome science and clinical practice. In this review, we explore recent advances in microbiome restitution by framing recovery as a dynamic ecological process shaped by complex interactions between microbial taxa, host physiology and environmental conditions. We review current evidence addressing four key questions that outline the salient ecology of perturbation and recovery: which microbial taxa are present in the microbiota and which taxonomic or functional qualities might increase susceptibility to perturbation; what is the nature of the perturbation, including the type and probable targets of the perturbation, as well as the indirect ecological and environmental consequences of that perturbation; what is the time course of perturbation and recovery, exploring prehabilitation strategies and successional trajectories as a staged recovery framework; and where does perturbation and recovery unfold in the gut, with attention to both regional and microscale spatial patterns. Highlighting recent advances from multi-omics approaches and longitudinal studies, we demonstrate how each of these factors and their interactions critically shape both robustness to disturbance and the trajectory of recovery. We advocate for multimodal, context-specific interventions that harness ecological principles to drive regrowth and community assembly, including diet, targeted microbial transplantation and modulation of the abiotic gut environment. Ultimately, resolving the challenge of microbiome restitution will require personalized strategies informed by ecological understanding and longitudinal functional monitoring. This paradigm provides a foundation for future translational advances to promote eubiosis and improve patient outcomes in microbiome-related diseases.
    Keywords:  Microbiome recovery; antibiotics; community assembly; diet; disturbance ecology; inflammation; perturbation; prehabilitation; resilience; secondary succession; stability
    DOI:  https://doi.org/10.1080/19490976.2026.2649448
  28. Drug Discov Today. 2026 Apr 21. pii: S1359-6446(26)00084-X. [Epub ahead of print] 104679
    Physics-inspired explainable AI for mechanistic and decision support in drug discovery.
    Antonio Lavecchia.
      Explainable artificial intelligence (XAI) is increasingly recognized as essential for trustworthy drug discovery, yet many approaches remain post hoc and correlational. This review examines physics-inspired XAI as a framework for improving mechanistic interpretability and decision support at the molecular design stage. We highlight its strengths in modeling molecular recognition and local structure-property relations, while emphasizing that efficacy and toxicity emerge from biological and pharmacological processes beyond molecular physics. Current evidence suggests that explainability improves prioritization and experimental efficiency, although its impact on overall R&D outcomes remains limited. We propose 'molecular intelligence' as a decision-centric framework integrating prediction, validation and domain knowledge.
    Keywords:  absorption, distribution, metabolism, excretion and toxicityprediction; drug discovery; explainable artificial intelligence; graph neural networks; molecular dynamics; physics-informed machine learning; structure–activity relations
    DOI:  https://doi.org/10.1016/j.drudis.2026.104679
  29. Int Dent J. 2026 Apr 22. pii: S0020-6539(26)00180-2. [Epub ahead of print]76(4): 109586
    Notch Signalling Pathway in the Pathogenesis of Periodontitis: Research Progress.
    Cheng Shang, Churen Zhang, Jianxia Hou.
       AIMS: This review examines the pivotal role of the Notch signalling pathway in the pathogenesis of periodontitis. We focus on its impact on the host inflammatory response, immune regulation, and alveolar bone homeostasis. By delineating how periodontal pathogens activate this pathway to exacerbate tissue damage, we also explore its potential as a therapeutic target.
    METHODS: This article synthesises and critically examines recent advances in research on the Notch signalling pathway in the context of periodontitis. By comprehensively reviewing and evaluating current literature, the methods include analysing mechanistic insights, experimental findings, and clinical evidence related to Notch signalling in periodontal pathogenesis.
    RESULTS: The review highlights that the Notch signalling pathway significantly influences the pathogenesis of periodontitis, impacting key disease processes such as inflammation, immune response, and tissue regeneration. It summarises evidence demonstrating the pathway's involvement in disease progression and its potential as a therapeutic target, while also identifying existing challenges and gaps in current knowledge.
    CONCLUSION: This review underscores the critical role of Notch signalling in periodontitis and contributes to a deeper understanding of the molecular mechanisms driving the disease. It encourages the development of novel therapeutic strategies and emphasises the need for further research to address unresolved questions and translate findings into clinical applications.
    Keywords:  Cell signalling; Inflammatory response; Notch signalling pathway; Pathogenesis; Periodontitis
    DOI:  https://doi.org/10.1016/j.identj.2026.109586
  30. BMC Oral Health. 2026 Apr 24.
    Clinical efficacy of Guided Biofilm Therapy in the management of periodontal disease - a systematic review.
    Nomita Yein, Santosh Martande, Sharath K Shetty, Anita Kulloli, Swathi Pv, Poornima Ramamurthy, Dileep Sharma.
      
    Keywords:  Air-polishing; Dental biofilm; Guided biofilm therapy; Non surgical periodontal therapy; Periodontal disease; Periodontal maintenance; Plaque
    DOI:  https://doi.org/10.1186/s12903-026-08418-z
  31. Nat Commun. 2026 Apr 18.
    Multi-kingdom profiling reveals altered gut phage-bacteria-metabolite interactions in MASLD.
    Xiaofeng Zhou, Da Zhou, Yanni Pu, Hanseul Kim, Zhonghan Sun, Wenhao Qi, Jiadong Jin, Wanqin Zhang, Mingfeng Xia, Chengyan Wang, Shangyu Hong, Long H Nguyen, Na Jiao, Yan Zheng, Taotao Liu.
      Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly linked to gut microbial dysbiosis, but most studies have focused on bacteria, neglecting viruses and fungi, and their interactions. Here we show that MASLD is characterized by coordinated disruption of bacterial, viral and fungal communities and by a disturbed phage-bacteria-metabolite axis associated with disease-related bile acid changes. Integrating shotgun metagenomics, fungal ITS2 sequencing, fecal metabolomics and clinical profiling in 210 patients with MASLD and 210 age- and gender-matched healthy controls, we find reduced microbial diversity and extensive remodeling of cross-kingdom ecological networks in MASLD. Ruminococcus gnavus emerges as an enriched central hub, while Faecalibacterium prausnitzii and its associated bacteriophages are depleted. Phage-host analyses further reveal reduced lytic activity against R. gnavus and loss of sulfur amino acid metabolism-related auxiliary metabolic genes, which may impair F. prausnitzii fitness. Diminished phage control may facilitate R. gnavus expansion, alongside increased fecal isodeoxycholic acid, a secondary bile acid implicated in hepatic steatosis. A diagnostic classifier integrating bacterial and viral features with clinical parameters distinguish MASLD from controls in our cohort and maintain predictive performance in two external datasets. Together, these findings uncover a disrupted phage-bacteria-metabolite axis in MASLD and provide a multi-kingdom framework for non-invasive biomarker discovery and microbiome-targeted therapies.
    DOI:  https://doi.org/10.1038/s41467-026-71981-0
  32. Infection. 2026 Apr 21.
    Multidrug-resistant Klebsiella pneumoniae in oncology intensive care units: selected genetic markers and clinical predictors.
    Aya El Nahas, Ahmed O El-Gendy, Mona Wassef, Fatma Molham.
       BACKGROUND: Multidrug-resistant (MDR) Klebsiella pneumoniae poses a critical threat in oncology intensive care units (ICUs), particularly in low- and middle-income countries like Egypt, where immunocompromised patients are at high risk from invasive procedures. This study aimed to characterize antimicrobial resistance patterns and molecular features of MDR K. pneumoniae isolates and to explore clinical and genetic markers associated with resistance burden.
    METHODS: Fifty K. pneumoniae isolates were recovered from cancer patients at Shefa Al Orman Oncology Hospital (Luxor, Egypt). Susceptibility testing was performed using VITEK® 2. Resistance genes (OmpK35, QnrB, AcrAB, OqxA, and Sul2) were detected via PCR. Resistance burden was quantified as a resistance score (R-score) and analyzed against clinical and genetic variables using non-parametric tests and regression models.
    RESULTS: All isolates (100%) were resistant to β-lactams. High resistance rates were observed for carbapenems (78-84%), fluoroquinolones (84%), aminoglycosides (76-80%), and trimethoprim-sulfamethoxazole (86%), while tetracycline (40%) and tigecycline (10%) showed lower resistance. Genetic analysis revealed Sul2 (100%), OmpK35 (94%), OqxA (92%), QnrB (90%), and AcrAB (68%). Prior hospitalization and antibiotic use within three months were the only independent risk factors for higher R-scores (p = 0.041). Patient mortality reached 46%.
    CONCLUSION: MDR K. pneumoniae in oncology ICUs shows extensive resistance and multiple genetic associations. Prior healthcare exposure significantly increases resistance burden, emphasizing the urgent need for stringent antimicrobial stewardship and targeted infection control measures.
    Keywords:   Klebsiella pneumoniae ; Carbapenem resistance; Intensive care unit (ICU); Multidrug resistance; Nosocomial infection; Sul2; Oncology patients
    DOI:  https://doi.org/10.1007/s15010-026-02793-z
  33. Curr Rev Clin Exp Pharmacol. 2026 Apr 13.
    Cannabidiol-Loaded Smart Hydrogels for Advanced Wound Healing: Drug Delivery Innovations and Therapeutic Perspectives.
    Ayushi Bhandari, Shikha Baghel Chauhan, Indu Singh, Chirag Jain.
      Chronic wounds are a leading healthcare burden worldwide, fueled by intricate pathophysiology and the inadequacy of standard therapies. The present review critically discusses the novel paradigm of incorporating cannabidiol (CBD), a phytocannabinoid with significant anti-inflammatory, antioxidant, antimicrobial, and pro-regenerative capacities, into advanced smart hydrogel platforms for better wound healing and tissue regeneration. We summarize the strong rationale for CBD, focusing on its multimodal pharmacological effects on central pathways (e.g., proinflammatory cytokines, oxidative stress, fibroblast activity, angiogenesis, endocannabinoid system) and reconciling its inherent delivery issues (poor solubility, instability, pharmacokinetics). The review comprehensively addresses the engineering of stimulus-responsive hydrogels (pH-, temperature-, enzyme-, redox-sensitive) to surmount these challenges. Material properties of key interest-biocompatibility, biodegradation tuneability, mechanical cues emulating ECM, and microenvironment control-are addressed together with innovative crosslinking mechanisms (dynamic covalent bonds, supramolecular interactions) as well as state-of-the-art fabrication techniques (3D/4D bioprinting, electrospinning, microfluidics). We have outlined the mechanisms of controlled release of CBD by wound-specific cues and investigated the synergistic interaction between CBD delivery dynamics and hydrogel characteristics in regulating key cellular events (macrophage polarization, re-epithelialization, ECM remodeling). Preclinical proof of principle for CBD-hydrogel therapeutic utility in various wound models (diabetic, infected, burn) is assessed, with discussion of the landscape of clinical translation, regulatory avenues, and ongoing challenges (scalability, standardization, long-term safety). Lastly, the review points to future frontiers such as closed-loop "sense-and-respond" systems, AI-assisted design, personalized point-of-- care manufacturing, and combinatorial strategies. We conclude that smart CBD-loaded hydrogels hold a promising approach to meeting unmet needs in treating chronic wounds by delivering localized, sustained, and physiologically responsive release to realize CBD's full therapeutic potential for regenerative medicine.
    Keywords:  Cannabidiol; chronic wounds; controlled drug delivery; regenerative medicine.; smart hydrogels; stimuli-responsive systems; tissue regeneration; wound healing
    DOI:  https://doi.org/10.2174/0127724328453813260323115317
  34. Future Microbiol. 2026 Apr 19. 1-17
    Novel antibacterials targeting multidrug-resistant gram-positive and gram-negative bacteria: an updated review.
    Yusuf Emre Ozdemir, Serkan Surme, Meryem Sahin Ozdemir, Khalis Mustafayev.
      The 2024 World Health Organization (WHO) bacterial priority pathogens list highlights third-generation cephalosporin-resistant and carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and rifampicin-resistant Mycobacterium tuberculosis as critical targets. Despite global efforts, antibiotic development remains limited, with 97 agents in the pipeline by 2023, one-third of which are directed against drug-resistant M. tuberculosis. Relevant data on novel antibacterial agents were identified through searches of the Scopus, PubMed, and Web of Science databases, as well as the 2024 WHO report on new and emerging antibiotics, focusing on studies published within the past 5 years. This review summarizes novel antibacterial agents targeting resistant Gram-negative and Gram-positive pathogens, including compounds that are currently under Food and Drug Administration evaluation or recently approved, as well as additional promising candidates under development for the treatment of drug-resistant microorganisms. In addition, a brief overview of the non-traditional agents that have completed the approval process and are now available on the market is also provided.
    Keywords:  Novel antibiotics; carbapenem-resistant Acinetobacter baumannii; extended-spectrum β-lactamase; multidrug-resistant Pseudomonas aeruginosa; multidrug-resistant enterobacterales
    DOI:  https://doi.org/10.1080/17460913.2026.2661277
  35. Health Sci Rep. 2026 Mar;9(3): e72034
    What We Can Do in Infectious Keratitis, Except for Conventional Antimicrobial-Based Therapies: Major Narrative Review.
    Kasra Cheraqpour.
       Background and Aims: Infectious keratitis (IK) is classified as a critical ophthalmic emergency, with the potential to result in vision-impairing complications. The treatment approach involves the use of pharmacological antimicrobial agents in combination with surgical interventions. Traditionally, the management of IK has relied on conventional antimicrobial agents, although the specific treatment regimen may vary based on the underlying causative agent. The growing antimicrobial resistance, along with the less favorable outcomes in most cases, emphasizes the urgent need for adjunctive or novel therapies. This report aims to provide a thorough overview of the current clinical and experimental non-antimicrobial therapies, encompassing both medical and surgical options, whether they serve as adjuncts to antimicrobial treatments or function as independent therapies for IK.
    Methods: A comprehensive search on PubMed was undertaken to identify relevant articles. Articles that described conventional antimicrobial-based treatments were excluded from the review. Additionally, case reports and non-English publications were not considered.
    Results: Various therapeutic options, including medical-based therapies (povidone-iodine, matrix metalloproteinases inhibitors, corticosteroids, host defense peptides, novel small molecules, formaldehyde releasers, synthetic polymers, antioxidants, and bacteriophages), laser/light-based therapies (photodynamic therapy, ultraviolet C light, thermal lasers, photothermal therapy, phototherapeutic keratectomy, and blue light), surgical-based therapies (conjunctival flap and Tenon graft, corneal gluing, amniotic membrane transplantation, and keratoplasty), and miscellaneous therapies (nanomedicine and contact lens, plasma ablation, debridement, and cryotherapy) were included and discussed.
    Conclusion: The conventional approach to managing IK involves the use of topical antimicrobial agents. Most instances can be effectively addressed with empirical treatment using antimicrobial eye drops, yielding satisfactory results. However, it seems the rise in antimicrobial resistance and insufficient response in some cases, especially fungal keratitis, necessitates ophthalmologists to utilize all currently available options in their toolbox more efficiently and intensify research efforts aimed at developing alternative therapeutic strategies.
    Keywords:  antimicrobial; corneal ulcer; keratitis; management; therapy; treatment
    DOI:  https://doi.org/10.1002/hsr2.72034
  36. JMIR Med Educ. 2026 Apr 20. 12 e86230
    From Anatomy to Innovation: Embedding Patient-Centered Design in Medical Education.
    Louis John Koizia, Pieter Vandekerckhove, Steven Howard, Bettina Maisch, Benjamin Howell Lole Harris.
       Unlabelled: Medical education has traditionally focused on mastering biomedical knowledge, clinical skills, and professionalism. Yet it remains poorly equipped to prepare doctors for the complex, rapidly changing health systems they will work in. Despite repeated calls for transformative learning, progress in teaching system innovation has been limited. Current curricula produce clinicians adept at treating disease but often underprepared to address system failures or contribute to organizational change. Embedding patient-centered innovation within training may help address this gap. This approach integrates design thinking, value-based health care, and co-design with patients to cultivate the metacompetence required to engage with system change. Emerging examples suggest that innovation education is most effective when integrated within existing activities such as quality improvement initiatives, multidisciplinary collaboration, and protected time for improvement work. Teaching these principles early may help normalize innovation as an integral component of clinical practice rather than a peripheral activity. Lessons from the successful integration of communication skills and ethics into medical curricula demonstrate that such cultural shifts are possible. Practical approaches may include incorporating design-thinking exercises, patient co-creation activities, and innovation projects alongside existing quality improvement and leadership programs. Reframing innovation as part of professional responsibility may empower clinicians to act as catalysts for system improvement. From anatomy to innovation, medical education must continue to evolve, preparing doctors not only to treat patients but also to engage with the systems that shape health care delivery.
    Keywords:  curriculum; educational innovation; reform; transformative learning; value-based health care
    DOI:  https://doi.org/10.2196/86230
  37. Paediatr Respir Rev. 2026 Apr 14. pii: S1526-0542(26)00027-8. [Epub ahead of print]
    Oral health status in adult and paediatric patients with cystic fibrosis (CF): A systematic review and meta-analysis.
    Alessandro Cuozzo, Leopoldo Mauriello, Vitolante Pezzella, Vincenzo Iorio-Siciliano, Elio Ramaglia, Sossio Giuseppe Lanzillo, Lorenzo Marini, Andrea Blasi.
      The aim of this study was to evaluate oral health in paediatric and adult patients affected by cystic fibrosis (CF). A systematic review was conducted following PRISMA guidelines. Electronic search was performed on scientific databases to identify studies reporting relevant oral health parameters. Eleven studies met inclusion criteria, mostly cross-sectional and from tertiary care settings. Paediatric CF cohorts showed caries risk comparable or lower than controls but a higher prevalence of developmental enamel defects (DDE) and altered salivary function. Adult CF patients exhibited increased DMFT scores with more untreated decay, while severe periodontitis (PD ≥ 6 mm) remained rare despite high plaque accumulation. CF is associated with a distinctive oral health profile, characterized by age-dependent caries risk, frequent enamel anomalies, altered salivary physiology, and relatively preserved periodontal status. Standardized longitudinal studies are needed to clarify these associations, evaluate CFTR modulators effects, and support the integration of dental care within multidisciplinary CF management.
    Keywords:  Cystic fibrosis; Dental caries; Enamel hypoplasia; Oral health; Periodontal diseases
    DOI:  https://doi.org/10.1016/j.prrv.2026.04.003
  38. Med Oral Patol Oral Cir Bucal. 2026 Apr 19. pii: 28134. [Epub ahead of print]
    Mapping scientific knowledge on the association between periodontal disease and rheumatoid arthritis: A bibliometric and altmetric analysis of the 100 most-cited articles.
    L-G Silvestrini, M-F Santos, B-D Rodrigues, L-M Gonzaga, H Martelli-Júnior, G-M Fabri, M-P Maia-Lima, L-M Ferreira.
       BACKGROUND: A bidirectional relationship between periodontal disease (PD) and rheumatoid arthritis (RA) has been widely investigated, highlighting the potential impact of oral diseases on systemic health. This bibliometric and altmetric analysis aimed to evaluate the 100 most-cited articles exploring the association between PD and RA.
    MATERIAL AND METHODS: A bibliometric review was conducted in accordance with the BIBLIO guidelines. The Scopus database was searched to identify the 100 most-cited articles, and citation counts were cross-validated in the Web of Science database. Data collected included publication year, citation counts, journals, authors, institutions, countries, study design, and collaboration patterns. Bibliometric networks were visualized using VOSviewer, altmetric data were obtained from the Dimensions platform, and public interest trends were analyzed using Google Trends.
    RESULTS: The selected articles accumulated 14,753 citations (mean: 147.5 citations per article). Scientific output increased in the 1990s, peaked between 2005 and 2015, and declined thereafter. Research production was concentrated in high-income countries, particularly the United States, the United Kingdom, and Australia, and the resulting articles were published in high-impact journals. The literature primarily focused on molecular mechanisms and biomarkers, whereas clinical trials were comparatively scarce. Altmetric scores demonstrated a weak but statistically significant (p=0.001) positive correlation with citation counts.
    CONCLUSIONS: This research field is well established and interdisciplinary, whose academic influence and public relevance are well documented. Nevertheless, limited geographic diversity and a relative paucity of interventional studies remain. Future multicenter and translational investigations are warranted to address these gaps and further advance clinical understanding.
    DOI:  https://doi.org/10.4317/medoral.28134
  39. Int J Nanomedicine. 2026 ;21 576258
    How Transformative Are ROS Responsive Hydrogel Nanoformulations to Treat Refractory Infected Wounds.
    Zongjunlin Liu, Hongqiong Xiang, Ke Xian, Lina Cai, Dui Yin, Jianqiao Zhong.
      Controlling infection in bacterial-infected wounds presents a formidable challenge, especially when compounded by additional high-risk factors that hinder the healing process during clinical interventions. Currently, the efficacy of standard therapeutic approaches often falls short, largely attributed to persistent local infections and inflammatory responses that impede healing cascades. In recent years, increasing reports on the management of hard-to-heal infected wounds have highlighted the potential of reactive oxygen species (ROS)-responsive hydrogels to facilitate wound recovery. The capacity of these hydrogels could be greatly enhanced by integrating them with traditional treatments, thereby addressing the complexities of healing in refractory infected wounds. Therefore, based on a thorough review of latest literatures, this paper comprehensively outlines the molecular mechanisms associated with hard-to-heal infected wounds, the role of ROS-responsive hydrogels in promoting healing, and a combined therapeutic strategy for wound control. It is designed to offer valuable insights to inform and advance future investigative efforts in this research field.
    Keywords:  ROS; combination therapy strategy; hard-to-heal infected wounds; hydrogel; nanoformulations; reactive oxygen species
    DOI:  https://doi.org/10.2147/IJN.S576258
  40. Bioact Mater. 2026 Sep;63 607-644
    Engineered piezoelectric dressings advance cutaneous wound healing.
    Zhao Chen, Hao Liu, Man Zhe, Ulrike Ritz, Fei Xing.
      Conventional wound dressings present inherent limitations in the therapeutic management of cutaneous wounds. Given the pivotal role of endogenous bioelectric fields in tissue repair, piezoelectric materials have emerged as a novel class of stimulus responsive biomaterials capable of transforming mechanical energy into biocompatible electrical signals, offering innovative solutions to address the bottlenecks of conventional interventions. Distinct from existing literature, this review demonstrates significant uniqueness by integrating the dual dimensions of breadth and depth. In terms of breadth, this review comprehensively covers and systematically categorizes a wide variety of piezoelectric dressing systems alongside their diverse stimulus responsive behaviors. In terms of depth, it not only profoundly elucidates the physical and chemical mechanisms underlying the piezoelectric effect and piezocatalysis, but also meticulously explores the key biological mechanisms through which they modulate multidimensional cellular behaviors and exert antibacterial effects. Building upon this foundation, the review systematically summarizes the current frontier application achievements of utilizing piezoelectric technologies for wound management. Finally, this review summarizes the major technical challenges and clinical translation bottlenecks facing piezoelectric dressings, and proposes highly promising future research directions, aiming to establish a solid theoretical framework and practical guidance for the development of piezoelectric wound management systems.
    Keywords:  Piezoelectric materials; Piezoelectricity; Stimulus-responsive biomaterials; Wound dressings; Wound healing
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.04.017
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