Pub Date : 2025-01-20Epub Date: 2024-12-06DOI: 10.1021/acsabm.4c01564
Ayda Ghahremanzadeh, Mehdi Ghaffari Sharaf, Marcello Tonelli, Larry D Unsworth
In 2023, around 850 million people globally were affected by chronic kidney disease, which leads to the retention of uremic toxins and excess fluid in the blood. This study examines the adsorption of these toxins to poly(ethylene oxide) (PEO) films, known for their low-fouling properties. The gold surfaces were treated with 5 mM end-thiolated methoxy-terminated PEO (m-PEO) and analyzed using dynamic contact angle measurements, X-ray photoelectron spectroscopy, and spectroscopic ellipsometry to confirm the PEO film's presence and determine chain density. The adsorption of 25 different uremic toxins to m-PEO films was evaluated by using liquid chromatography-mass spectrometry (LC/MS), focusing on their binding affinity and adsorption dynamics. Results showed the effective modification of surfaces with m-PEO, with a notable change in contact angles and chain density (∼0.5 and 0.8 chains/nm2). Interestingly, pyruvic acid showed significant adsorption, whereas other toxins, such as hippuric acid, creatinine, and xanthosine had minimal interactions with the film. This indicates that the adsorption of these toxins is not primarily concentration driven and is rather dependent on the chemical structure of each toxin. These findings provide important insights for designing low-fouling coatings for biomedical devices.
{"title":"Effect of End-Tethered Methoxy-PEO Chain Density on Uremic Toxin Adsorption.","authors":"Ayda Ghahremanzadeh, Mehdi Ghaffari Sharaf, Marcello Tonelli, Larry D Unsworth","doi":"10.1021/acsabm.4c01564","DOIUrl":"10.1021/acsabm.4c01564","url":null,"abstract":"<p><p>In 2023, around 850 million people globally were affected by chronic kidney disease, which leads to the retention of uremic toxins and excess fluid in the blood. This study examines the adsorption of these toxins to poly(ethylene oxide) (PEO) films, known for their low-fouling properties. The gold surfaces were treated with 5 mM end-thiolated methoxy-terminated PEO (<i>m</i>-PEO) and analyzed using dynamic contact angle measurements, X-ray photoelectron spectroscopy, and spectroscopic ellipsometry to confirm the PEO film's presence and determine chain density. The adsorption of 25 different uremic toxins to <i>m</i>-PEO films was evaluated by using liquid chromatography-mass spectrometry (LC/MS), focusing on their binding affinity and adsorption dynamics. Results showed the effective modification of surfaces with <i>m</i>-PEO, with a notable change in contact angles and chain density (∼0.5 and 0.8 chains/nm<sup>2</sup>). Interestingly, pyruvic acid showed significant adsorption, whereas other toxins, such as hippuric acid, creatinine, and xanthosine had minimal interactions with the film. This indicates that the adsorption of these toxins is not primarily concentration driven and is rather dependent on the chemical structure of each toxin. These findings provide important insights for designing low-fouling coatings for biomedical devices.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"704-714"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20Epub Date: 2024-12-12DOI: 10.1021/acsabm.4c01348
Junhong Fan, Fengli An, Shaohua Li, Yuqin Guo, Haolan Zhang, Yaxin Zhang, Yujie Cao, Lan Yu
Antibiotic misuse and bacterial resistance are pressing issues threatening public health. Natural plant extracts with bactericidal properties offer potential alternatives to reduce or replace antibiotic use. This study aims to develop a thermosensitive hydrogel containing daphnetin (DAP-TG) using poloxamers 407 (P407), polyvinylpyrrolidone (PVP), and poloxamers 188 (P188). We systematically evaluated the gel's antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as well as its antibacterial mechanisms. By examining the gelation temperature and time, degradation time, and in vitro release performance of DAP-TG, we produced a sustained-release DAP-TG with a rapid phase transition at (31.6 ± 0.1) °C. Its structure was characterized through Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The results indicated that the DAP thermosensitive hydrogel was formed and presented a 3D network spatial structure. The biocompatibility of DAP-TG was explored through the hemolysis test and cytotoxicity test. The results indicated that DAP-TG possessed excellent biocompatibility. The antibacterial efficacy of DAP-TG against E. coli and S. aureus was assessed using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), growth curve, and inhibition zone tests. Results showed that DAP-TG exhibited excellent antibacterial activity against both E. coli and S. aureus, with MIC values of 1.28 and 0.32 mg/mL. The antibacterial mechanism of DAP-TG was preliminarily explored through the investigation of bacterial cell content leakage, AKP leakage, membrane permeability, SEM, ROS production, and biofilm inhibition activity. DAP-TG induced irreversible damage to the cell membranes of E. coli and S. aureus, resulting in enhanced permeability, elevated ROS levels, and inhibited biofilm formation. Our study indicates that DAP-TG exhibits effective sustained-release and antibacterial properties against E. coli and S. aureus in vitro, making it a promising candidate for antibacterial applications in food and pharmaceutical products.
{"title":"Preparation and Antibacterial Activity Evaluation of Daphnetin-Loaded Poloxamers/Polyvinylpyrrolidone Thermosensitive Hydrogels.","authors":"Junhong Fan, Fengli An, Shaohua Li, Yuqin Guo, Haolan Zhang, Yaxin Zhang, Yujie Cao, Lan Yu","doi":"10.1021/acsabm.4c01348","DOIUrl":"10.1021/acsabm.4c01348","url":null,"abstract":"<p><p>Antibiotic misuse and bacterial resistance are pressing issues threatening public health. Natural plant extracts with bactericidal properties offer potential alternatives to reduce or replace antibiotic use. This study aims to develop a thermosensitive hydrogel containing daphnetin (DAP-TG) using poloxamers 407 (P407), polyvinylpyrrolidone (PVP), and poloxamers 188 (P188). We systematically evaluated the gel's antibacterial activity against <i><i>Escherichia coli</i></i> (<i>E. coli</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>), as well as its antibacterial mechanisms. By examining the gelation temperature and time, degradation time, and in vitro release performance of DAP-TG, we produced a sustained-release DAP-TG with a rapid phase transition at (31.6 ± 0.1) °C. Its structure was characterized through Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The results indicated that the DAP thermosensitive hydrogel was formed and presented a 3D network spatial structure. The biocompatibility of DAP-TG was explored through the hemolysis test and cytotoxicity test. The results indicated that DAP-TG possessed excellent biocompatibility. The antibacterial efficacy of DAP-TG against <i>E. coli</i> and <i>S. aureus</i> was assessed using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), growth curve, and inhibition zone tests. Results showed that DAP-TG exhibited excellent antibacterial activity against both <i>E. coli</i> and <i>S. aureus</i>, with MIC values of 1.28 and 0.32 mg/mL. The antibacterial mechanism of DAP-TG was preliminarily explored through the investigation of bacterial cell content leakage, AKP leakage, membrane permeability, SEM, ROS production, and biofilm inhibition activity. DAP-TG induced irreversible damage to the cell membranes of <i>E. coli</i> and <i>S. aureus</i>, resulting in enhanced permeability, elevated ROS levels, and inhibited biofilm formation. Our study indicates that DAP-TG exhibits effective sustained-release and antibacterial properties against <i>E. coli</i> and <i>S. aureus</i> in vitro, making it a promising candidate for antibacterial applications in food and pharmaceutical products.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"374-385"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20Epub Date: 2024-12-26DOI: 10.1021/acsabm.4c01651
Xiaolan Mai, Yu Hu, Zhenlin Wu, Xin Guo, Mingming Dong, Lingyun Jia, Jun Ren
Recent clinical studies have highlighted the presence of microclots in the form of amyloid fibrinogen particles (AFPs) in plasma samples from Long COVID patients. However, the clinical significance of these abnormal, nonfibrillar self-assembly aggregates of human fibrinogen remains debated due to the limited understanding of their structural and biological characteristics. In this study, we present a method for generating mimetic microclots in vitro. Using this approach, the self-assembly process, structural organization of AFPs, and their interactions with human plasma components were elucidated. The amyloid transition of fibrinogen occurs under acidic conditions within a pH range of 2.3-3.2. Well-dispersed amyloid oligomers of fibrinogen, ranging in size from 1 to 5 μm, can be prepared at pH 2.8 after 1 h of incubation. We tracked the dynamic self-assembly process at the single-molecule level using high-speed atomic force microscopy (HS-AFM). The arrangement of amyloid oligomers manifests as well-ordered, stacked nanodomains with striped patterns, growing perpendicular to the primary axis of the fibrinogen monomer. Upon transfer to physiological solution conditions or human plasma, these amyloid oligomers further aggregate into nonfibrillar structures at the micrometer scale, resembling the microclots observed in the bloodstream of Long COVID patients. Notably, these AFPs exhibit characteristics consistent with microclots, including positive staining in thioflavin T (ThT) assays and resistance to fibrinolysis. Proteomic analysis suggests that AFPs interact with various components of human plasma and have an enhanced binding affinity with complement C3 compared to native fibrinogen. This study enables the in vitro preparation of mimetic microclots exhibiting amyloid features. It is anticipated to facilitate further researches on the mechanisms, detection, and treatment of diseases associated with fibrinogen amyloidogenesis.
{"title":"Self-Assembly of Human Fibrinogen into Microclot-Mimicking Antifibrinolytic Amyloid Fibrinogen Particles.","authors":"Xiaolan Mai, Yu Hu, Zhenlin Wu, Xin Guo, Mingming Dong, Lingyun Jia, Jun Ren","doi":"10.1021/acsabm.4c01651","DOIUrl":"10.1021/acsabm.4c01651","url":null,"abstract":"<p><p>Recent clinical studies have highlighted the presence of microclots in the form of amyloid fibrinogen particles (AFPs) in plasma samples from Long COVID patients. However, the clinical significance of these abnormal, nonfibrillar self-assembly aggregates of human fibrinogen remains debated due to the limited understanding of their structural and biological characteristics. In this study, we present a method for generating mimetic microclots in vitro. Using this approach, the self-assembly process, structural organization of AFPs, and their interactions with human plasma components were elucidated. The amyloid transition of fibrinogen occurs under acidic conditions within a pH range of 2.3-3.2. Well-dispersed amyloid oligomers of fibrinogen, ranging in size from 1 to 5 μm, can be prepared at pH 2.8 after 1 h of incubation. We tracked the dynamic self-assembly process at the single-molecule level using high-speed atomic force microscopy (HS-AFM). The arrangement of amyloid oligomers manifests as well-ordered, stacked nanodomains with striped patterns, growing perpendicular to the primary axis of the fibrinogen monomer. Upon transfer to physiological solution conditions or human plasma, these amyloid oligomers further aggregate into nonfibrillar structures at the micrometer scale, resembling the microclots observed in the bloodstream of Long COVID patients. Notably, these AFPs exhibit characteristics consistent with microclots, including positive staining in thioflavin T (ThT) assays and resistance to fibrinolysis. Proteomic analysis suggests that AFPs interact with various components of human plasma and have an enhanced binding affinity with complement C3 compared to native fibrinogen. This study enables the in vitro preparation of mimetic microclots exhibiting amyloid features. It is anticipated to facilitate further researches on the mechanisms, detection, and treatment of diseases associated with fibrinogen amyloidogenesis.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"825-834"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20Epub Date: 2025-01-09DOI: 10.1021/acsabm.4c01733
Thanh Mai Nguyen Tran, M N Prabhakar, Lee Dong Woo, Song Jung-Il
The current work presents the flame-retardant performance of hybrid polypropylene composites, reinforced with specific short woven flax fabrics (SWFs), short basalt fibers (BFs), and rice husk powder (RHP), using polypropylene grafted maleic anhydride (MAPP) as the coupling agent. Horizontal burning test (HBT), microcalorimeter test (MCT), and cone calorimeter test (CCT) were conducted on these composites. The formulations used were 25% SWF/PP, 25% SWF/20% BF/PP, and 25% SWF/20% BF/PP with 6% RHP and 25% SWF/20% BF/PP with varying RHP contents (6, 12, and 18%) in combination with 6% MAPP. A peak heat release rate (pHRR) reduction of 14.42% was recorded in microcalorimeter test results. However, cone calorimeter test results indicated a reduction of 80.95% in pHRR and 23.84% in total heat release rate (THR). Furthermore, the emissions of CO and CO2 were reduced by 68 and 67%, respectively, in the 25SWF/20BF/PP.6MAPP-18RHP composite compared to pure PP, indicating an overall improvement in combustion efficiency. Fire performance index (FPI) also improved remarkably: FPI increased by 130% and fire growth index (FGI) improved by 81.34%. Moreover, the horizontal burning test showed an improved performance, with the burning rate further reduced by 11.10% compared to that of the 25% SWF/PP composite. These results highlight the synergy among natural fibers, agro-waste fillers, and MAPP in improving flame retardancy of polypropylene composites, and hence their potential application in automobiles and construction, where the demand for fire safety is very high.
{"title":"Flame Retardancy and Heat Shielding in Green Polypropylene Composites Using Biohybrid Fibers and Agro-Waste Fillers.","authors":"Thanh Mai Nguyen Tran, M N Prabhakar, Lee Dong Woo, Song Jung-Il","doi":"10.1021/acsabm.4c01733","DOIUrl":"10.1021/acsabm.4c01733","url":null,"abstract":"<p><p>The current work presents the flame-retardant performance of hybrid polypropylene composites, reinforced with specific short woven flax fabrics (SWFs), short basalt fibers (BFs), and rice husk powder (RHP), using polypropylene grafted maleic anhydride (MAPP) as the coupling agent. Horizontal burning test (HBT), microcalorimeter test (MCT), and cone calorimeter test (CCT) were conducted on these composites. The formulations used were 25% SWF/PP, 25% SWF/20% BF/PP, and 25% SWF/20% BF/PP with 6% RHP and 25% SWF/20% BF/PP with varying RHP contents (6, 12, and 18%) in combination with 6% MAPP. A peak heat release rate (pHRR) reduction of 14.42% was recorded in microcalorimeter test results. However, cone calorimeter test results indicated a reduction of 80.95% in pHRR and 23.84% in total heat release rate (THR). Furthermore, the emissions of CO and CO<sub>2</sub> were reduced by 68 and 67%, respectively, in the 25SWF/20BF/PP.6MAPP-18RHP composite compared to pure PP, indicating an overall improvement in combustion efficiency. Fire performance index (FPI) also improved remarkably: FPI increased by 130% and fire growth index (FGI) improved by 81.34%. Moreover, the horizontal burning test showed an improved performance, with the burning rate further reduced by 11.10% compared to that of the 25% SWF/PP composite. These results highlight the synergy among natural fibers, agro-waste fillers, and MAPP in improving flame retardancy of polypropylene composites, and hence their potential application in automobiles and construction, where the demand for fire safety is very high.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"893-902"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20Epub Date: 2024-12-13DOI: 10.1021/acsabm.4c01442
Yuqian Sang, Ziyang Zhang, Qian Ren, Junlun Zhu, Yan He
The growing threat of bacterial resistance is a critical global health concern, necessitating the development of more efficient methods for evaluating antimicrobial efficacy. Here, we introduce a technique based on the sensitivity of bacterial collective motion to environmental changes, using motion trajectory analysis for swift antibiotic susceptibility appraisal within a simple spread-out of bacterial droplet. By single cell tracking in bacterial fluids near the droplet edge or boundary-detection of the colony expansion, we achieved rapid evaluation of antibiotic efficacy in under 60 min. This method is not only faster than traditional assays but also provides insights into drug-bacterial interactions, offering a powerful tool for advancing both diagnostic testing and the development of antimicrobial agents.
{"title":"Rapid Evaluation of Antimicrobial Potency Through Bacterial Collective Motion Analysis.","authors":"Yuqian Sang, Ziyang Zhang, Qian Ren, Junlun Zhu, Yan He","doi":"10.1021/acsabm.4c01442","DOIUrl":"10.1021/acsabm.4c01442","url":null,"abstract":"<p><p>The growing threat of bacterial resistance is a critical global health concern, necessitating the development of more efficient methods for evaluating antimicrobial efficacy. Here, we introduce a technique based on the sensitivity of bacterial collective motion to environmental changes, using motion trajectory analysis for swift antibiotic susceptibility appraisal within a simple spread-out of bacterial droplet. By single cell tracking in bacterial fluids near the droplet edge or boundary-detection of the colony expansion, we achieved rapid evaluation of antibiotic efficacy in under 60 min. This method is not only faster than traditional assays but also provides insights into drug-bacterial interactions, offering a powerful tool for advancing both diagnostic testing and the development of antimicrobial agents.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"519-526"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20Epub Date: 2024-12-31DOI: 10.1021/acsabm.4c01204
Yonghua Su, Cuiling Ding, Yaqiong Zhou, Yi Ning Xu, Peng Fei Liu, Xiaoying Sun, Siwei Fan, Haiyu Wu, Tiancheng Zeng, Haoran Peng, Bin Li
SARS-CoV-2 is a threat to global public health, which requires the development of safe measures to reduce the spread of this coronavirus. Herein, in this study, we prepared and examined potential antiviral agents based on ZnAl-layered double hydroxide (ZnAl-LDH) materials. ZnAl-LDH-based samples were synthesized via a one-pot low-temperature coprecipitation method, which features an ultrathin structure. The incorporation of trace amounts of Ag induces the formation of ZnO particles on the ZnAl-LDH surface, where both ZnO and Ag enhance UV light absorption. Interestingly, ZnAl-LDH-Ag shows a significantly high anticoronavirus effect upon exposure to the daylight lamp of the operation console and ultraviolet light. Moreover, ZnAl-LDH and ZnAl-LDH-Ag potently blocked the entry of SARS-CoV-2 pseudoparticles to cells. The in vivo biocompatibility experiment has demonstrated that ZnAl-LDH-Ag is a potentially biocompatible and potent anti-SARS-CoV-2 agent for virus prevention. The synergistic interactions between these nanoparticles continuously generate reactive oxygen species (ROS), leading to effective and sustained viral inactivation. This light-sensitive ROS production introduces a photocatalytic inactivation mechanism in antiviral materials. Moreover, unlike conventional antiviral agents that rapidly deplete their active components, the layered structure of this composite enables the controlled long-term release of antiviral radicals, enhancing its durability. ZnAl-LDH-Ag has been expected to be a promising solution for long-lasting antiviral applications.
{"title":"Colloidal ZnAl-Layered Double Hydroxide Nanomaterials for Effective Prevention of SARS-CoV-2.","authors":"Yonghua Su, Cuiling Ding, Yaqiong Zhou, Yi Ning Xu, Peng Fei Liu, Xiaoying Sun, Siwei Fan, Haiyu Wu, Tiancheng Zeng, Haoran Peng, Bin Li","doi":"10.1021/acsabm.4c01204","DOIUrl":"10.1021/acsabm.4c01204","url":null,"abstract":"<p><p>SARS-CoV-2 is a threat to global public health, which requires the development of safe measures to reduce the spread of this coronavirus. Herein, in this study, we prepared and examined potential antiviral agents based on ZnAl-layered double hydroxide (ZnAl-LDH) materials. ZnAl-LDH-based samples were synthesized via a one-pot low-temperature coprecipitation method, which features an ultrathin structure. The incorporation of trace amounts of Ag induces the formation of ZnO particles on the ZnAl-LDH surface, where both ZnO and Ag enhance UV light absorption. Interestingly, ZnAl-LDH-Ag shows a significantly high anticoronavirus effect upon exposure to the daylight lamp of the operation console and ultraviolet light. Moreover, ZnAl-LDH and ZnAl-LDH-Ag potently blocked the entry of SARS-CoV-2 pseudoparticles to cells. The in vivo biocompatibility experiment has demonstrated that ZnAl-LDH-Ag is a potentially biocompatible and potent anti-SARS-CoV-2 agent for virus prevention. The synergistic interactions between these nanoparticles continuously generate reactive oxygen species (ROS), leading to effective and sustained viral inactivation. This light-sensitive ROS production introduces a photocatalytic inactivation mechanism in antiviral materials. Moreover, unlike conventional antiviral agents that rapidly deplete their active components, the layered structure of this composite enables the controlled long-term release of antiviral radicals, enhancing its durability. ZnAl-LDH-Ag has been expected to be a promising solution for long-lasting antiviral applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"329-340"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The rapid emergence of multidrug-resistant (MDR) bacteria represents a critical global health threat, underscoring the urgent need for alternative antimicrobial strategies beyond conventional antibiotics. In this study, we report the synthesis of novel biobased antimicrobial polymers bearing quaternary ammonium salts, derived from sustainable feedstocks, maleic anhydride, dimethylaminobenzaldehyde, and furfurylamine. The functional tricyclic oxanorbornene lactam monomer is polymerized via ring opening metathesis polymerization, yielding well-defined polymers with controlled molar masses and low dispersity. Structural characterization is performed using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and the polymerization kinetics is monitored by online 1H NMR spectroscopy. The quaternized biobased polymers demonstrate potent broad-spectrum antimicrobial activity against three clinically isolated MDR bacterial strains. They exhibit minimum inhibitory concentrations (MICs) that are significantly lower than those of several conventional antibiotics while also showing low hemolytic activity toward mammalian cells. This study highlights the potential of bioderived ROMP polymers as promising, sustainable antimicrobial polymers for combating the growing threat of antimicrobial resistance.
{"title":"Antimicrobial Polymer via ROMP of a Bioderived Tricyclic Oxanorbornene Lactam Derivative.","authors":"Mohamed A Yassin, Hartmut Komber, Mohamed Naguib, Mohamed Abdelraof, Dietmar Appelhans, Brigitte Voit","doi":"10.1021/acsabm.4c01924","DOIUrl":"https://doi.org/10.1021/acsabm.4c01924","url":null,"abstract":"<p><p>The rapid emergence of multidrug-resistant (MDR) bacteria represents a critical global health threat, underscoring the urgent need for alternative antimicrobial strategies beyond conventional antibiotics. In this study, we report the synthesis of novel biobased antimicrobial polymers bearing quaternary ammonium salts, derived from sustainable feedstocks, maleic anhydride, dimethylaminobenzaldehyde, and furfurylamine. The functional tricyclic oxanorbornene lactam monomer is polymerized via ring opening metathesis polymerization, yielding well-defined polymers with controlled molar masses and low dispersity. Structural characterization is performed using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and the polymerization kinetics is monitored by online <sup>1</sup>H NMR spectroscopy. The quaternized biobased polymers demonstrate potent broad-spectrum antimicrobial activity against three clinically isolated MDR bacterial strains. They exhibit minimum inhibitory concentrations (MICs) that are significantly lower than those of several conventional antibiotics while also showing low hemolytic activity toward mammalian cells. This study highlights the potential of bioderived ROMP polymers as promising, sustainable antimicrobial polymers for combating the growing threat of antimicrobial resistance.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20Epub Date: 2024-12-29DOI: 10.1021/acsabm.4c01613
Si-Yuan Zhou, Lei Li, Jian-Hua Cao, Xiu-Bin Yang, Da-Yong Wu
Chitosan is generally considered to be a procoagulant effect, which may cause adverse phenomena such as blood clotting when used in small-diameter vascular grafts. However, it also shows good biocompatibility and anti-inflammatory properties, which can facilitate vascular reconstruction. Therefore, it is significant to transition the effect of chitosan from coagulation promotion to antiplatelet while still harnessing its bioactivity. The procoagulant mechanism of chitosan is primarily attributed to the presence of protonated amino groups in the molecular chain. If the number of amino groups in chitosan is reduced, the procoagulant effect will be diminished as well. Aspirin has a strong antiplatelet function, and its molecular structure contains numerous active carboxyl groups, which can couple with the amino groups in chitosan. Aspirin-modified chitosan retains the biological activity of chitosan while also imparting an antiplatelet effect. In our study, we used a heparinized electrospun graft as the substrate and coated it with aspirin-modified chitosan to create a functional vascular graft. The blood clotting index of the graft remained above 80% after 45 min, and the platelet activation degree was only 4.03%. Additionally, the graft maintained complete patency with stable blood flow after 4 weeks of implantation and the vascular structure was largely rebuilt.
{"title":"Transition from Procoagulation to Antiplatelet Effect: Application and Mechanism of Aspirin-Modified Chitosan in Small-Diameter Vascular Grafts.","authors":"Si-Yuan Zhou, Lei Li, Jian-Hua Cao, Xiu-Bin Yang, Da-Yong Wu","doi":"10.1021/acsabm.4c01613","DOIUrl":"https://doi.org/10.1021/acsabm.4c01613","url":null,"abstract":"<p><p>Chitosan is generally considered to be a procoagulant effect, which may cause adverse phenomena such as blood clotting when used in small-diameter vascular grafts. However, it also shows good biocompatibility and anti-inflammatory properties, which can facilitate vascular reconstruction. Therefore, it is significant to transition the effect of chitosan from coagulation promotion to antiplatelet while still harnessing its bioactivity. The procoagulant mechanism of chitosan is primarily attributed to the presence of protonated amino groups in the molecular chain. If the number of amino groups in chitosan is reduced, the procoagulant effect will be diminished as well. Aspirin has a strong antiplatelet function, and its molecular structure contains numerous active carboxyl groups, which can couple with the amino groups in chitosan. Aspirin-modified chitosan retains the biological activity of chitosan while also imparting an antiplatelet effect. In our study, we used a heparinized electrospun graft as the substrate and coated it with aspirin-modified chitosan to create a functional vascular graft. The blood clotting index of the graft remained above 80% after 45 min, and the platelet activation degree was only 4.03%. Additionally, the graft maintained complete patency with stable blood flow after 4 weeks of implantation and the vascular structure was largely rebuilt.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 1","pages":"763-773"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20Epub Date: 2024-12-20DOI: 10.1021/acsabm.4c01497
Amanda de Souza, Cintia C S Martignago, Lívia Assis, Fernanda Vieira Botelho Delpupo, Marcelo Assis, Karolyne S J Sousa, Lais Caroline Souza E Silva, Laura O Líbero, Flavia de Oliveira, Ana Claudia Muniz Renno
Skin wounds are extremely frequent injuries related to many etiologies. They are a burden on healthcare systems worldwide. Skin dressings are the most popular therapy, and collagen is the most commonly used biomaterial, although new sources of collagen have been studied, especially spongin-like from marine sponges (SPG), as a promising source due to a similar composition to vertebrates and the ability to function as a cell-matrix adhesion framework. Despite evidence showing the positive effects of SPG for tissue healing, the effects of skin dressings manufactured are still limited. In this context, this study aimed at investigating the effects of collagen skin dressings in an experimental model of skin wounds in rats. For this purpose, SEM, FTIR, cell viability, morphological and morphometric aspects, collagen deposition, and immunostaining of TGF-β and FGF were evaluated. The results demonstrated micro- and macropores on the rough surface, peak characteristics of collagen, and no cytotoxicity for the skin dressing. Also, the control group (CG) after 5 and 10 days exhibited an intense inflammatory process and the presence of granulation tissue, while the treated group (TG) exhibited re-epithelialization after 10 days. The evaluation of granulation tissue and neoepithelial length had an intragroup statistical difference (p = 0.0216) and no intergroup difference. Birefringence demonstrated an organized mesh arranged in a network pattern, presenting type I and type III collagen fibers in all groups. Moreover, in the morphometric evaluation, there were no statistical differences in intergroups or time points for the different types of collagen evaluated. In conclusion, these findings may indicate that the dressing has not exacerbated the inflammatory process and may allow faster healing. However, further studies using a critical wound healing injury model should be used, associated with longer experimental periods of evaluation, to further investigate the effects of these promising therapeutic approaches throughout the skin repair process.
皮肤伤口是一种极为常见的伤害,与多种病因有关。它们是全球医疗系统的负担。皮肤敷料是最流行的治疗方法,而胶原蛋白是最常用的生物材料,尽管人们一直在研究胶原蛋白的新来源,特别是来自海洋海绵的类海绵蛋白(SPG),由于其成分与脊椎动物相似,并具有细胞基质粘附框架的功能,因此是一种很有前景的来源。尽管有证据显示 SPG 对组织愈合有积极作用,但制造的皮肤敷料的效果仍然有限。在这种情况下,本研究旨在调查胶原蛋白皮肤敷料在大鼠皮肤伤口实验模型中的效果。为此,研究人员对扫描电镜、傅立叶变换红外光谱、细胞存活率、形态和形态计量学方面、胶原沉积以及 TGF-β 和 FGF 的免疫染色进行了评估。结果表明,皮肤敷料的粗糙表面存在微孔和大孔,胶原蛋白具有峰值特征,而且没有细胞毒性。此外,对照组(CG)在 5 天和 10 天后显示出强烈的炎症过程和肉芽组织的存在,而治疗组(TG)在 10 天后显示出再上皮化。肉芽组织和新生上皮长度的评估在组内有统计学差异(p = 0.0216),组间无差异。双折射显示,所有组的肉芽组织均呈有组织的网状排列,并呈现 I 型和 III 型胶原纤维。此外,在形态学评估中,不同类型的胶原蛋白在组间或时间点上均无统计学差异。总之,这些研究结果可能表明,敷料并没有加剧炎症过程,可能会加快伤口愈合。不过,还应该使用临界伤口愈合损伤模型进行进一步研究,并延长评估的实验时间,以进一步研究这些有前景的治疗方法在整个皮肤修复过程中的效果。
{"title":"Casting Skin Dressing Containing Extractions of the Organic Part of Marine Sponges for Wound Healing.","authors":"Amanda de Souza, Cintia C S Martignago, Lívia Assis, Fernanda Vieira Botelho Delpupo, Marcelo Assis, Karolyne S J Sousa, Lais Caroline Souza E Silva, Laura O Líbero, Flavia de Oliveira, Ana Claudia Muniz Renno","doi":"10.1021/acsabm.4c01497","DOIUrl":"10.1021/acsabm.4c01497","url":null,"abstract":"<p><p>Skin wounds are extremely frequent injuries related to many etiologies. They are a burden on healthcare systems worldwide. Skin dressings are the most popular therapy, and collagen is the most commonly used biomaterial, although new sources of collagen have been studied, especially spongin-like from marine sponges (SPG), as a promising source due to a similar composition to vertebrates and the ability to function as a cell-matrix adhesion framework. Despite evidence showing the positive effects of SPG for tissue healing, the effects of skin dressings manufactured are still limited. In this context, this study aimed at investigating the effects of collagen skin dressings in an experimental model of skin wounds in rats. For this purpose, SEM, FTIR, cell viability, morphological and morphometric aspects, collagen deposition, and immunostaining of TGF-β and FGF were evaluated. The results demonstrated micro- and macropores on the rough surface, peak characteristics of collagen, and no cytotoxicity for the skin dressing. Also, the control group (CG) after 5 and 10 days exhibited an intense inflammatory process and the presence of granulation tissue, while the treated group (TG) exhibited re-epithelialization after 10 days. The evaluation of granulation tissue and neoepithelial length had an intragroup statistical difference (<i>p</i> = 0.0216) and no intergroup difference. Birefringence demonstrated an organized mesh arranged in a network pattern, presenting type I and type III collagen fibers in all groups. Moreover, in the morphometric evaluation, there were no statistical differences in intergroups or time points for the different types of collagen evaluated. In conclusion, these findings may indicate that the dressing has not exacerbated the inflammatory process and may allow faster healing. However, further studies using a critical wound healing injury model should be used, associated with longer experimental periods of evaluation, to further investigate the effects of these promising therapeutic approaches throughout the skin repair process.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"617-627"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20Epub Date: 2025-01-06DOI: 10.1021/acsabm.4c01432
Soemwit Khongwichit, Piyawut Swangphon, Aekkaraj Nualla-Ong, Napat Prompat, Maliwan Amatatongchai, Peter A Lieberzeit, Suticha Chunta
The accumulation of oxidized low-density lipoprotein (oxLDL) in macrophages leads to the formation of foam cells and atherosclerosis development. Reducing the uptake of oxLDL in macrophages decreases the incidence and progression of atherosclerosis. Four distinct single-strand DNA sequences, namely, AP07, AP11, AP25, and AP29, were selected that demonstrated specific binding to distinct regions of oxidized apolipoprotein B100 (apoB100; the protein component of oxLDL) with low HDOCK scores. These four DNA sequences were combined to generate aptamers that selectively bound to labeled Dil-oxLDL, and were subsequently added to murine RAW 264.7 macrophages to test their inhibitory effects using fluorescence spectrometry. The four combined aptamers at 10 μM reduced oxLDL uptake by 79 ± 4% compared to that of the untreated aptamer group. Flow cytometry data demonstrated that macrophages treated with aptamers reached only 32.6% of the Dil-oxLDL signal, a 50% reduction in fluorescence emission relative to that of the untreated group (64.4% Dil-oxLDL signal). Binding the four combined aptamers to the oxLDL surface disrupted the interaction between oxLDL and CD36 via cyclic voltammetry, effectively decreasing the level of uptake of oxLDL by macrophages. Results suggested that these aptamers could be used as alternative compounds to prevent the formation of foam cells, hence providing antiatherosclerosis activity.
{"title":"Reduced Uptake of Oxidized Low-Density Lipoprotein by Macrophages Using Multiple Aptamer Combinations.","authors":"Soemwit Khongwichit, Piyawut Swangphon, Aekkaraj Nualla-Ong, Napat Prompat, Maliwan Amatatongchai, Peter A Lieberzeit, Suticha Chunta","doi":"10.1021/acsabm.4c01432","DOIUrl":"10.1021/acsabm.4c01432","url":null,"abstract":"<p><p>The accumulation of oxidized low-density lipoprotein (oxLDL) in macrophages leads to the formation of foam cells and atherosclerosis development. Reducing the uptake of oxLDL in macrophages decreases the incidence and progression of atherosclerosis. Four distinct single-strand DNA sequences, namely, AP07, AP11, AP25, and AP29, were selected that demonstrated specific binding to distinct regions of oxidized apolipoprotein B100 (apoB100; the protein component of oxLDL) with low HDOCK scores. These four DNA sequences were combined to generate aptamers that selectively bound to labeled Dil-oxLDL, and were subsequently added to murine RAW 264.7 macrophages to test their inhibitory effects using fluorescence spectrometry. The four combined aptamers at 10 μM reduced oxLDL uptake by 79 ± 4% compared to that of the untreated aptamer group. Flow cytometry data demonstrated that macrophages treated with aptamers reached only 32.6% of the Dil-oxLDL signal, a 50% reduction in fluorescence emission relative to that of the untreated group (64.4% Dil-oxLDL signal). Binding the four combined aptamers to the oxLDL surface disrupted the interaction between oxLDL and CD36 via cyclic voltammetry, effectively decreasing the level of uptake of oxLDL by macrophages. Results suggested that these aptamers could be used as alternative compounds to prevent the formation of foam cells, hence providing antiatherosclerosis activity.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 1","pages":"457-474"},"PeriodicalIF":4.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}