Persistent Bacterial Infections Research Articles

Modeling airway persistent infection of Moraxella catarrhalis and nontypeable Haemophilus influenzae by using human in vitro models.

Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are two common respiratory tract pathogens often associated with acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) as well as with otitis media (OM) in children. Although there is evidence that these pathogens can adopt persistence mechanisms such as biofilm formation, the precise means through which they contribute to disease severity and chronicity remains incompletely understood, posing challenges for their effective eradication. The identification of potential vaccine candidates frequently entails the characterization of the host-pathogen interplay in vitro even though this approach is limited by the fact that conventional models do not permit long term bacterial infections. In the present work, by using air-liquid-interface (ALI) human airway in vitro models, we aimed to recreate COPD-related persistent bacterial infections. In particular, we explored an alternative use of the ALI system consisting in the assembly of an inverted epithelium grown on the basal part of a transwell membrane with the aim to enable the functionality of natural defense mechanisms such as mucociliary clearance and cellular extrusion that are usually hampered during conventional ALI infection experiments. The inversion of the epithelium did not affect tissue differentiation and considerably delayed NTHi or Mcat infection progression, allowing one to monitor host-pathogen interactions for up to three weeks. Notably, the use of these models, coupled with confocal and transmission electron microscopy, revealed unique features associated with NTHi and Mcat infection, highlighting persistence strategies including the formation of intracellular bacterial communities (IBCs) and surface-associated biofilm-like structures. Overall, this study demonstrates the possibility to perform long term host-pathogen investigations in vitro with the aim to define persistence mechanisms adopted by respiratory pathogens and individuate potential new vaccine targets.

Healing with precision: A multi-functional hydrogel-bioactive glass dressing boosts infected wound recovery and enhances neurogenesis in the wound bed

Chronic skin wounds, especially infected ones, pose a significant clinical challenge due to their increasing incidence and poor outcomes. The deteriorative microenvironment in such wounds, characterized by reduced extracellular matrix, impaired angiogenesis, insufficient neurogenesis, and persistent bacterial infection, has prompted the exploration of novel therapeutic strategies. In this study, we developed an injectable multifunctional hydrogel (GEL/BG@Cu + Mg) incorporating Gelatin-Tannic acid/ N-hydroxysuccinimide functionalized polyethylene glycol and Bioactive glass doped with copper and magnesium ions to accelerate the healing of infected wounds. The GEL/BG@Cu + Mg hydrogel composite demonstrates good biocompatibility, degradability, and rapid formation of a protective barrier to stop bleeding. Synergistic bactericidal effects are achieved through the photothermal properties of BG@Cu + Mg and sustained copper ions release, with the latter further promoting angiogenesis. Furthermore, the hydrogel enhances neurogenesis by stimulating axons and Schwann cells in the wound bed through the beneficial effects of magnesium ions. Our results demonstrate that the designed novel multifunctional hydrogel holds tremendous promise for treating infected wounds and allowing regenerative neurogenesis at the wound site, which provides a viable alternative for further improving clinical outcomes.

Nuclear factor kappa B-dependent persistence of Salmonella Typhi and Paratyphi in human macrophages.

Salmonella enterica is a common cause of gastrointestinal infections worldwide. The serovars Salmonella Typhi and Salmonella Paratyphi A cause a distinctive systemic illness called enteric fever, whose pathogenesis is incompletely understood. Here, we show that enteric fever Salmonella serovars lack 12 specific virulence factors possessed by nontyphoidal Salmonella serovars, which allow the enteric fever serovars to persist within human macrophages. We propose that this fundamental difference in the interaction of Salmonella with human macrophages is responsible for the chronicity of typhoid and paratyphoid fever, suggesting that targeting the nuclear factor κB (NF-κB) complex responsible for macrophage survival could facilitate the clearance of persistent bacterial infections.

Beyond the β-amino alcohols framework: identification of novel β-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases. A series of novel β-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an EC50 value of 0.28 μg mL-1. A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analyses of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity:71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo. Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. This article is protected by copyright. All rights reserved.

Light-responsive Au@Zn-TCPP nanozyme functionalized with cell-penetrating peptide and antisense oligonucleotide for sensing living bacteria and synergistic therapy of diabetic wounds

The persistent bacterial infections in diabetic-induced woundspose a significantsocietal burden,requiringinnovative antimicrobial agentsandeffectivebacteria biosensor. In thisstudy, we successfully developeda composite antimicrobial nanomaterial (Au@Zn-Tcpp/ASO-pVEC NSs)that combines acell-penetrating peptide-conjugated two-dimensional MOF with adaptive photo-responsive integration of biosensor diagnosis and therapy. Various in vitro antimicrobial experimentsdemonstrated that Au@Zn-Tcpp/ASO-pVEC NSsachieved99.99% inhibition against both E. coli and S. aureus under laser irradiation and glucose catalysis. Additionally, Au@Zn-Tcpp/ASO-pVEC NSsexhibitedsustained release of ROS and excellent photothermal properties.Furthermore, in the context of wound infections, Au@Zn-Tcpp/ASO-pVEC NSsshowed optimal skin wound healing,with less than 2% residual infected area against diabetic bacterial infections and significantly reduced inflammation. Moreover, these nanomaterials demonstrated the capability to effectively detect bacteria throughfluorescent polypeptide probe.Overall,this antimicrobial strategy, whichcombines sensing living bacteria with a multimodal approach comprising chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT),holds substantial potential forproviding timelyclinical treatments andreliable monitoring of bacterial infections.

Genomic Characterization of Multidrug-Resistant Pathogenic Enteric Bacteria from Healthy Children in Osun State, Nigeria.

Antimicrobial resistance (AMR) is responsible for the spread and persistence of bacterial infections. Surveillance of AMR in healthy individuals is usually not considered, though these individuals serve as reservoirs for continuous disease transmission. Therefore, it is essential to conduct epidemiological surveillance of AMR in healthy individuals to fully understand the dynamics of AMR transmission in Nigeria. Thirteen multidrug-resistant Citrobacter spp., Enterobacter spp., Klebsiella pneumoniae, and Escherichia coli isolated from stool samples of healthy children were subjected to whole genome sequencing (WGS) using Illumina and Oxford nanopore sequencing platforms. A bioinformatics analysis revealed antimicrobial resistance genes such as the pmrB_Y358N gene responsible for colistin resistance detected in E. coli ST219, virulence genes such as senB, and ybtP&Q, and plasmids in the isolates sequenced. All isolates harbored more than three plasmid replicons of either the Col and/or Inc type. Plasmid reconstruction revealed an integrated tetA gene, a toxin production caa gene in two E. coli isolates, and a cusC gene in K. quasivariicola ST3879, which induces neonatal meningitis. The global spread of AMR pathogenic enteric bacteria is of concern, and surveillance should be extended to healthy individuals, especially children. WGS for epidemiological surveillance will improve the detection of AMR pathogens for management and control.

Revolution of Helicobacter pylori treatment.

Helicobacter pylori infection is a major global health concern, and its management has witnessed a revolutionary shift with the emergence of antibiotic resistance. In this review, I explore the mechanisms of H.pylori antibiotic resistance and highlight the critical need for susceptibility-based eradication treatments. The increasing prevalence of antibiotic-resistant strains requires innovative approaches to combat this resilient pathogen. I also delve into the importance of mass screening as a preventive strategy for early detection and intervention, describing my experience in Bhutan. Additionally, I explore promising alternatives, such as vaccination. The aim of this review is to provide insight into the evolving landscape of H.pylori treatment and highlight the need for a paradigm shift in the approach to combating this persistent bacterial infection.

An efficient deep learning network with orthogonal softmax layer for automatic detection of tuberculosis

Tuberculosis (TB) is a persistent bacterial lung infection that affects the lungs severely. It is one of the fatal diseases among the top ten leading causes of death. Thus, early and accurate diagnosis of TB precisely has vital role in saving lives. In this work, a novel Deep Learning Network with Orthogonal SoftMax Layer (OSL) is proposed for the detection of Tuberculosis (TB) that yields admirable performance in small medical datasets. The integrated merits of deep learning-based efficient feature extraction and OSL-based classification boost the classification performance. OSL enhances discriminative feature learning capability by maintaining orthogonality among weight vectors in this layer. It is also responsible for reducing the co-adaption among parameters and making optimization easier. In addition, data augmentation is done in the training stage using a customized version of RandAugment to train the network properly, even with small medical datasets. The experimental results depict the proposed deep learning network outperforms others with the best 98.67% accuracy, 98.99% precision, 98.33% sensitivity, 99.00% specificity, and 0.9866 F1 score.

Tailored gelatin methacryloyl-based hydrogel with near-infrared responsive delivery of Qiai essential oils boosting reactive oxygen species scavenging, antimicrobial, and anti-inflammatory activities for diabetic wound healing

The management of diabetic wounds poses a substantial economic and medical burden for diabetic patients. Oxidative stress and persistent bacterial infections are considered to be the primary factors. Qiai essential oil (QEO) exhibits various pharmacological characteristics, including inflammatory-reducing, antibacterial, and antioxidant properties. Nevertheless, the hydrophobic nature and propensity for explosive release of this substance present constraints on its potential for future applications. Here, we developed a stimulus-responsive hydrogel to overcome the multiple limitations of QEO-based wound dressings. The QEO was encapsulated within graphene oxide (GO) through repeated extrusion using an extruder. Subsequently, QEO@GO nanoparticles were incorporated into a Gelatin-methacryloyl (GelMA) hydrogel. The QEO@GO-GelMA hydrogel demonstrated controlled release ablation, photothermal antibacterial effects, and contact ablation against two representative bacterial strains. It effectively reduced reactive oxygen species (ROS) generation, promoted angiogenesis, and decreased levels of the pro-inflammatory cytokine interleukin-6 (IL-6), thereby accelerating the healing process of diabetic wounds. In addition, in vitro and in vivo tests provided further evidence of the favorable biocompatibility of this multifunctional hydrogel dressing. Overall, the QEO@GO-GelMA hydrogel provides numerous benefits, encompassing antimicrobial properties, ROS-scavenging abilities, anti-inflammatory effects, and the capacity to expedite diabetic wound healing. These attributes make it an optimal choice for diabetic wound management.

Hyaluronic acid-decorated curcumin-based coordination nanomedicine for enhancing the infected diabetic wound healing

Persistent over-oxidation, inflammation and bacterial infection are the primary reasons for impaired wound repairing in diabetic patients. Therefore, crucial strategies to promote diabetic wound repairing involve suppressing the inflammatory response, inhibiting bacterial growth and decreasing reactive oxygen species (ROS) within the wound. In this work, we develop a multifunctional nanomedicine (HA@Cur/Cu) designed to facilitate the repairing process of diabetic wound. The findings demonstrated that the synthesized infinite coordination polymers (ICPs) was effective in enhancing the bioavailability of curcumin and improving the controlled drug release at the site of inflammation. Furthermore, in vitro and in vivo evaluation validate the capacity of HA@Cur/Cu to inhibit bacterial growth and remove excess ROS and inflammatory mediators, thereby significantly promoting the healing of diabetic wound in mice. These compelling findings strongly demonstrate the enormous promise of this multifunctional nanomedicine for the treatment of diabetic wound.

Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University

Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked the centennial of Felix d’Hérelle’s first publication on the clinical applications of phages. At the Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established to offer safe and potent phages for single-patient investigational new drug applications while recognizing the time constraints imposed by infection(s). This study provides a practical walkthrough of the pipeline with an Autographiviridae phage targeting Pseudomonas aeruginosa (phage vB_PaeA_SB, abbreviated to ΦSB). Notably, a thorough phage characterization and the evolutionary selection pressure exerted on bacteria by phages, analogous to antibiotics, are incorporated into the pipeline.

Crystal structure of vancomycin bound to the resistance determinant D-alanine-D-serine.

Vancomycin is a glycopeptide antibiotic that for decades has been a mainstay of treatment for persistent bacterial infections. However, the spread of antibiotic resistance threatens its continued utility. In particular, vancomycin-resistant enterococci (VRE) have become a pressing clinical challenge. Vancomycin acts by binding and sequestering the intermediate Lipid II in cell-wall biosynthesis, specifically recognizing a D-alanine-D-alanine dipeptide motif within the Lipid II molecule. VRE achieve resistance by remodeling this motif to either D-alanine-D-lactate or D-alanine-D-serine; the former substitution essentially abolishes recognition by vancomycin of Lipid II, whereas the latter reduces the affinity of the antibiotic by roughly one order of magnitude. The complex of vancomycin bound to D-alanine-D-serine has been crystallized, and its 1.20 Å X-ray crystal structure is presented here. This structure reveals that the D-alanine-D-serine ligand is bound in essentially the same position and same pose as the native D-alanine-D-alanine ligand. The serine-containing ligand appears to be slightly too large to be comfortably accommodated in this way, suggesting one possible contribution to the reduced binding affinity. In addition, two flexible hydroxyl groups - one from the serine side chain of the ligand, and the other from a glucose sugar on the antibiotic - are locked into single conformations in the complex, which is likely to contribute an unfavorable entropic component to the recognition of the serine-containing ligand.

DP1, a multifaceted synthetic peptide: Mechanism of action, activity and clinical potential

AimsMicrobial infections remain a leading cause of mortality worldwide, with Staphylococcus aureus (S. aureus) being a prominent etiological agent, responsible for causing persistent bacterial infections in humans. It is a nosocomial, opportunistic pathogen, capable to propagate within the bloodstream and withstand therapeutic interventions. In the current study, a novel, indigenously designed synthetic antimicrobial peptide (sAMP) has been evaluated for its antimicrobial potential to inhibit the growth and proliferation of S. aureus. Main methodsThe sAMP, designed peptide (DP1) was evaluated for its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against a panel of pathogenic bacterial strains. Membrane mechanistic studies were performed by measuring membrane conductivity via dielectric spectroscopy and visualizing changes in bacterial membrane structure through field emission scanning electron microscopy (FE-SEM). Further, DP1 was tested for its in vivo antimicrobial potential in an S. aureus-induced systemic infection model. Key findingsThe results indicated that DP1 has the potential to inhibit the growth and proliferation of a broad spectrum of Gram-positive, Gram-negative and multidrug-resistant (MDR) bacterial strains. Strong bactericidal effect attributed to change in electrical conductivity of the bacterial cells leading to membrane disruption was observed through dielectric spectroscopy and FE-SEM micrographs. Further, in the in vivo murine systemic infection study, 50 % reduction in S. aureus bioburden was observed within 1 day of the administration of DP1. SignificanceThe results indicate that DP1 is a multifaceted peptide with potent bactericidal, antioxidant and therapeutic properties. It holds significance as a novel drug candidate to effectively combat S. aureus-mediated systemic infections.

Phage Paride can kill dormant, antibiotic-tolerant cells of Pseudomonas aeruginosa by direct lytic replication

Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly in a slow- or non-growing, dormant state. Here, we show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates (“hibernation”). However, a newly isolated Pseudomonas aeruginosa phage, named Paride, can directly replicate and induce the lysis of deep-dormant hosts. While non-growing bacteria are notoriously tolerant to antibiotic drugs, the combination with Paride enables the carbapenem meropenem to eradicate deep-dormant cultures in vitro and to reduce a resilient bacterial infection of a tissue cage implant in mice. Our work might inspire new treatments for persistent bacterial infections and, more broadly, highlights two viral strategies to infect dormant bacteria (hibernation and direct replication) that will guide future studies on phage-host interactions.

Cas-based bacterial detection: recent advances and perspectives.

Persistent bacterial infections pose a formidable threat to global health, contributing to widespread challenges in areas such as food safety, medical hygiene, and animal husbandry. Addressing this peril demands the urgent implementation of swift and highly sensitive detection methodologies suitable for point-of-care testing and large-scale screening. These methodologies play a pivotal role in the identification of pathogenic bacteria, discerning drug-resistant strains, and managing and treating diseases. Fortunately, new technology, the CRISPR/Cas system, has emerged. The clustered regularly interspaced short joint repeats (CRISPR) system, which is part of bacterial adaptive immunity, has already played a huge role in the field of gene editing. It has been employed as a diagnostic tool for virus detection, featuring high sensitivity, specificity, and single-nucleotide resolution. When applied to bacterial detection, it also surpasses expectations. In this review, we summarise recent advances in the detection of bacteria such as Mycobacterium tuberculosis (MTB), methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (E. coli), Salmonella and Acinetobacter baumannii (A. baumannii) using the CRISPR/Cas system. We emphasize the significance and benefits of this methodology, showcasing the capability of diverse effector proteins to swiftly and precisely recognize bacterial pathogens. Furthermore, the CRISPR/Cas system exhibits promise in the identification of antibiotic-resistant strains. Nevertheless, this technology is not without challenges that need to be resolved. For example, CRISPR/Cas systems must overcome natural off-target effects and require high-quality nucleic acid samples to improve sensitivity and specificity. In addition, limited applicability due to the protospacer adjacent motif (PAM) needs to be addressed to increase its versatility. Despite the challenges, we are optimistic about the future of bacterial detection using CRISPR/Cas. We have already highlighted its potential in medical microbiology. As research progresses, this technology will revolutionize the detection of bacterial infections.

A self-healing injectable hydrogel integrated with enzymatic and nonenzymatic antioxidants as artificial antioxidant defense system for diabetic wound healing

Chronic diabetic wounds seriously threaten human health due to their intractable nature in a complex pathological microenvironment that contains oxidative stress, persistent inflammatory status, hypoxia and bacterial infections, of which oxidative damage contributing the most. Applied materials that can mimic the natural intracellular antioxidant defense system are perceived to have huge therapeutic potential. Herein, we present a novel strategy to prepare a versatile nanocomposite hydrogel by incorporating the nanoenzyme (manganese dioxide (MnO2)) and nonenzymatic antioxidant components (polydopamine (PDA)) in a dynamic hydrogel network composed of thioctic acid and tannic acid (TA). The prepared hydrogel exhibited outstanding adhesive and injectable properties, making it adapt perfectly to wounds with different shapes and depths. More importantly, encapsulation of PDA@MnO2 nanoparticles (NPs) conferred the hydrogel with superior antioxidant performance to effectively scavenge multiple types of reactive nitrogen and oxygen species (RNOS) and reduce the inflammatory response by regulating macrophage polarization. Meanwhile, the hydrogel showed high-performance catalyzing ability to transfer hydrogen peroxide (H2O2) into oxygen (O2), which could further alleviate hypoxic wound environment. Moreover, the nanocomposite hydrogel exhibited excellent near-infrared (NIR) photothermal antibacterial effect. Collectively, our findings indicate that the synthesized nanocomposite hydrogel shows potential for use in a clinical setting to treat diabetic wounds.

Machine learning enabled multiplex detection of periodontal pathogens by surface-enhanced Raman spectroscopy

Periodontitis is a chronic inflammation of the periodontium caused by a persistent bacterial infection, resulting in destruction of the supporting structures of teeth. Analysis of microbial composition in saliva can inform periodontal status. Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Streptococcus mutans (Sm) are among reported periodontal pathogens, and were used as model systems in this study. Our atomic force microscopic (AFM) study revealed that these pathogens are biological nanorods with dimensions of 0.6–1.1 μm in length and 500–700 nm in width. Current bacterial detection methods often involve complex preparation steps and require labeled reporting motifs. Employing surface-enhanced Raman spectroscopy (SERS), we revealed cell-type specific Raman signatures of these pathogens for label-free detection. It overcame the complexity associated with spectral overlaps among different bacterial species, relying on high signal-to-noise ratio (SNR) spectra carefully collected from pure species samples. To enable simple, rapid, and multiplexed detection, we harnessed advanced machine learning techniques to establish predictive models based on a large set of raw spectra of each bacterial species and their mixtures. Using these models, given a raw spectrum collected from a bacterial suspension, simultaneous identification of all three species in the test sample was achieved at 95.6 % accuracy. This sensing modality can be applied to multiplex detection of a broader range and a larger set of periodontal pathogens, paving the way for hassle-free detection of oral bacteria in saliva with little to no sample preparation.

Bacterial infection and microbiota in carcinogenesis and tumor development.

Microbiota colonize exposed body tissues (e.g., gastrointestinal tract, skin, lungs, female genital tract, and urogenital tracts) and unexposed sites (e.g., breast). Persistent bacterial infection in the host lead to the development of multiple disease. They are implicated in the pathogenesis of various complex diseases, including diabetes, atherosclerosis, autoimmune diseases, Alzheimer's disease, and malignant diseases. Amounting studies have demonstrated the role of bacterial infection in carcinogenesis. The study of microbiota in tumorigenesis is primarily focused on lung cancer, colorectal cancer (CRC), breast cancer, gastric cancer, and gynecologic tumors, and so on. Infection of Helicobacter pylori in gastric cancer carcinogenesis is recognized as class I carcinogen by the World Health Organization (WHO) decades ago. The role of Fusobacterium nucleatum in the development of colorectal cancer is extensively investigated. Variable bacteria have been cultured from the tumor tissues. The identification of microbiota in multiple tumor tissues reveal that bacterial infection and microbiota are associated with tumor development. The microbiota affects multiple aspects of carcinogenesis and tumor development, including favoring epithelial cells proliferation, establishing inflammatory microenvironment, promoting metastasis, and causing resistance to therapy. On the other hand, microbiota can shape a tumor surveillance environment by enhancing cell activity, and sensitize the tumor cells to immune therapy. In the present review, the roles of microbiota in multiple malignancies are summarized, and unraveling the mechanisms of host-microbiota interactions can contribute to a better understanding of the interaction between microbiota and host cells, also the development of potential anti-tumor therapeutic strategies.

Multifunctional DNA-Based Hydrogel Promotes Diabetic Alveolar Bone Defect Reconstruction.

Diabetic alveolar bone defect (DABD) causes persistent bacterial infection, prolonged inflammation, and delayed bone healing, making it a considerable clinical challenge. In this study, by integrating silver nanoclusters (AgNCs) and M2 macrophage-derived extracellular vesicles (M2EVs), a multifunctional DNA-based hydrogel, called Agevgel, is developed with antibacterial, anti-inflammatory, immunomodulatory, and osteogenic properties to promote DABD rebuilding. AgNCs are tightly embedded into the DNA scaffolds and exhibit effective anti-bacterial activity, while immunomodulatory M2EVs are encapsulated within the shape-variable DNA scaffolds and exhibit potent anti-inflammatory and osteogenic properties. The results reveal that Agevgel effectively prolongs the local retention time and bioactivity of M2EVs in vivo. In particular, the sustained release of M2EVs can last for at least 7 days when applying Agevgel to DABD. Compared to free M2EVs or Aggel (AgNCs encapsulated within the DNA hydrogel) treatments, the Agevgel treatment accelerates the defect healing rate of alveolar bone and dramatically improves the trabecular architecture. Mechanistically, Agevgel plays a key role in regulating macrophage polarization and promoting the expression of proliferative and osteogenic factors. In summary, Agevgel provides a comprehensive treatment strategy for DABD with a great clinical translational value, highlighting the application of DNA hydrogels as an ideal bioscaffolds for periodontal diseases.

Dynamic Microenvironment-Adaptable Hydrogel with Photothermal Performance and ROS Scavenging for Management of Diabetic Ulcer.

Persistent bacterial infections and excessive oxidative stress prevent the healing of diabetic ulcers, leading to an increased disability rate. Current treatments fail to kill bacteria while simultaneously relieving oxidative stress. Herein, a dynamic microenvironment-adaptable hydrogel (BP@CAu) with photothermal performance and reactive oxygen species scavenging is presented for diabetic ulcer healing. This hydrogel prepared using a dynamic borate-ester could respond to acidity in the infection microenvironment for a controllable drug release. An excellent photothermal conversion effect was integrated in the hydrogel, which exhibited strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The hydrogel attenuated intracellular oxidative stress and inflammation and promoted cell migration. In a full-thickness skin defect model of diabetic rats, the BP@CAu hydrogel contributed to the fastest wound closure, with ideal reepithelialization, granulation tissue formation, and regeneration of blood vessels. Further mechanistic studies revealed that the hydrogel relieved oxidative stress and downregulated the expression of inflammatory cytokines, resulting in dramatic therapeutic effects on diabetic wounds. Therefore, this study provides a synergistic therapeutic strategy for efficient photothermal performance and reactive oxygen species scavenging in diabetic ulcers.