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Design of strong and tough biofibers and their biomedical applications
Pub Date : 2025-02-19 DOI: 10.1002/mba2.70005
Dongpeng Sun, Yuan Zheng, Anxun Zhang, Jing Wang, Yao Xiao, Dong Chen

Strong and tough biofibers, which have comparable mechanical performances with conventional synthetic fibers derived from petrochemicals, have demonstrated superior advantages in sustainability and biocompatibility and have provided innovative solutions for various areas over synthetic fibers. Studies on strong and tough biofibers have addressed the growing demand for sustainable products and biomedical applications. Here, recent advances in strong and tough biofibers are summarized and discussed, including their materials, spinning methods, strengthening strategies, and various applications. Four natural materials commonly used for biofibers are introduced first, including spider silk, silkworm silk, chitin, and cellulose, and then four different spinning techniques developed to prepare strong and tough biofibers are summarized, including dry spinning, wet spinning, 3D printing, and microfluidic spinning. Strengthening strategies, such as dual crosslinking and post treatment, are applied to further improve the mechanical performances of biofibers, and their applications, especially in clothing, suture, would dressing, tissue engineering, and sensor, are discussed in detail. Continuous innovations in strong and tough biofibers hold a great promise for driving further advancements and offering solutions to related global challenges.

{"title":"Design of strong and tough biofibers and their biomedical applications","authors":"Dongpeng Sun,&nbsp;Yuan Zheng,&nbsp;Anxun Zhang,&nbsp;Jing Wang,&nbsp;Yao Xiao,&nbsp;Dong Chen","doi":"10.1002/mba2.70005","DOIUrl":"https://doi.org/10.1002/mba2.70005","url":null,"abstract":"<p>Strong and tough biofibers, which have comparable mechanical performances with conventional synthetic fibers derived from petrochemicals, have demonstrated superior advantages in sustainability and biocompatibility and have provided innovative solutions for various areas over synthetic fibers. Studies on strong and tough biofibers have addressed the growing demand for sustainable products and biomedical applications. Here, recent advances in strong and tough biofibers are summarized and discussed, including their materials, spinning methods, strengthening strategies, and various applications. Four natural materials commonly used for biofibers are introduced first, including spider silk, silkworm silk, chitin, and cellulose, and then four different spinning techniques developed to prepare strong and tough biofibers are summarized, including dry spinning, wet spinning, 3D printing, and microfluidic spinning. Strengthening strategies, such as dual crosslinking and post treatment, are applied to further improve the mechanical performances of biofibers, and their applications, especially in clothing, suture, would dressing, tissue engineering, and sensor, are discussed in detail. Continuous innovations in strong and tough biofibers hold a great promise for driving further advancements and offering solutions to related global challenges.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446710","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}
引用次数: 0
One-pot synthesis of tunable fluorescent polyethylene glycol (PEG) polymer for antimicrobial and anticancer theranostics
Pub Date : 2025-02-09 DOI: 10.1002/mba2.70004
Dokkari Nagalaxmi Yadav, Dinesh Harijan, Sunil Venkanna Pogu, Ganesan Prabusankar, Aravind Kumar Rengan

Poly (ethylene glycol) (PEG), is a well-known biocompatible and biodegradable polymer with a wide range of applications such as surface coating of nano/micro materials for improving their biocompatibility, immunological inertness, and systemic circulation. However, PEG is a nonfluorescent material limiting its application in bioimaging. So herein, a novel fluorescent PEG polymer was synthesized using a facile method. For this, in-house water-soluble compound [4,5-bis-{(N- carboxy methyl benzimidazolium) methyl} acridine] dibromide}] (b-ACA) was synthesized and used to modify nonfluorescent PEG polymer into a novel fluorescent PEG polymer (PEG-b-ACA) by one-pot method. PEG-b-ACA displayed a range of fluorescence from green to red with respect to the concentration of b-ACA being used. The synthesized PEG-b-ACA mixture was evaluated for its antimicrobial and antiviral efficacy against E. coli, S. aureus, C. albicans, and Bacteriophage Lambda, and it showed significant inhibition of microbial and viral growth. The mixture was also evaluated for its cellular uptake and anticancer efficacy using 4T1 breast cancer cells, and it showed significant results in both. The results demonstrated that the PEG-b-ACA mixture is a potent antimicrobial, antiviral, and anticancer agent when compared with PEG and b-ACA alone. Therefore, the synthesized PEG-b-ACA mixture could be an effective material for various biomedical applications.

{"title":"One-pot synthesis of tunable fluorescent polyethylene glycol (PEG) polymer for antimicrobial and anticancer theranostics","authors":"Dokkari Nagalaxmi Yadav,&nbsp;Dinesh Harijan,&nbsp;Sunil Venkanna Pogu,&nbsp;Ganesan Prabusankar,&nbsp;Aravind Kumar Rengan","doi":"10.1002/mba2.70004","DOIUrl":"https://doi.org/10.1002/mba2.70004","url":null,"abstract":"<p>Poly (ethylene glycol) (PEG), is a well-known biocompatible and biodegradable polymer with a wide range of applications such as surface coating of nano/micro materials for improving their biocompatibility, immunological inertness, and systemic circulation. However, PEG is a nonfluorescent material limiting its application in bioimaging. So herein, a novel fluorescent PEG polymer was synthesized using a facile method. For this, in-house water-soluble compound [4,5-bis-{(N- carboxy methyl benzimidazolium) methyl} acridine] dibromide}] (b-ACA) was synthesized and used to modify nonfluorescent PEG polymer into a novel fluorescent PEG polymer (PEG-b-ACA) by one-pot method. PEG-b-ACA displayed a range of fluorescence from green to red with respect to the concentration of b-ACA being used. The synthesized PEG-b-ACA mixture was evaluated for its antimicrobial and antiviral efficacy against <i>E. coli, S. aureus, C. albicans</i>, and Bacteriophage Lambda, and it showed significant inhibition of microbial and viral growth. The mixture was also evaluated for its cellular uptake and anticancer efficacy using 4T1 breast cancer cells, and it showed significant results in both. The results demonstrated that the PEG-b-ACA mixture is a potent antimicrobial, antiviral, and anticancer agent when compared with PEG and b-ACA alone. Therefore, the synthesized PEG-b-ACA mixture could be an effective material for various biomedical applications.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380233","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}
引用次数: 0
Biofilm formation in cardiovascular infection and bioengineering approaches for treatment and prevention
Pub Date : 2025-01-31 DOI: 10.1002/mba2.70003
Qi Tong, Qiyue Xu, Jie Cai, Yiren Sun, Zhengjie Wang, Yongjun Qian

At present, cardiovascular infection such as infective endocarditis (IE) has become a major disease with a high mortality rate. The essence of IE is actually the infection associated with biofilm formation, which can occur not only on native heart valves, but also on prosthetic heart valves and cardiovascular implants such as left heart assist devices, vascular grafts, and pacemakers. Biofilms are bacterial aggregates that are composed of a self-produced extracellular polymeric substance (EPS), which is difficult and challenging for the treatment of cardiovascular infections. Therefore, it is important to explore and develop effective anti-biofilm methods for the treatment of biofilm-associated cardiovascular infection. This review provides comprehension of strategies for degrading EPS in biofilm, the application of nanodrug delivery systems for biofilm-related infections, the strategy for targeting drug resistance genes through gene editing technology and strategy for targeting quorum sensing in biofilm. Furthermore, this review also provides some strategies to optimize the antibacterial properties of cardiovascular implants to prevent biofilm formation. The applications of these strategies will provide novel preventive and therapeutic ways for biofilm-associated cardiovascular infections.

{"title":"Biofilm formation in cardiovascular infection and bioengineering approaches for treatment and prevention","authors":"Qi Tong,&nbsp;Qiyue Xu,&nbsp;Jie Cai,&nbsp;Yiren Sun,&nbsp;Zhengjie Wang,&nbsp;Yongjun Qian","doi":"10.1002/mba2.70003","DOIUrl":"https://doi.org/10.1002/mba2.70003","url":null,"abstract":"<p>At present, cardiovascular infection such as infective endocarditis (IE) has become a major disease with a high mortality rate. The essence of IE is actually the infection associated with biofilm formation, which can occur not only on native heart valves, but also on prosthetic heart valves and cardiovascular implants such as left heart assist devices, vascular grafts, and pacemakers. Biofilms are bacterial aggregates that are composed of a self-produced extracellular polymeric substance (EPS), which is difficult and challenging for the treatment of cardiovascular infections. Therefore, it is important to explore and develop effective anti-biofilm methods for the treatment of biofilm-associated cardiovascular infection. This review provides comprehension of strategies for degrading EPS in biofilm, the application of nanodrug delivery systems for biofilm-related infections, the strategy for targeting drug resistance genes through gene editing technology and strategy for targeting quorum sensing in biofilm. Furthermore, this review also provides some strategies to optimize the antibacterial properties of cardiovascular implants to prevent biofilm formation. The applications of these strategies will provide novel preventive and therapeutic ways for biofilm-associated cardiovascular infections.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121499","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}
引用次数: 0
Simultaneous detection of dual targets Escherichia coli and Salmonella enteritidis using enzyme-free strand displacement reaction
Pub Date : 2025-01-19 DOI: 10.1002/mba2.70002
Shixin Yan, Yuling Xiao, Ruijuan Shen, Jiazhe Cheng, Yuling Zhang, Nan Wu, Jinhao Chen, Jie Chen, Peng Zhang, Jia Geng

Escherichia coli (E. coli) and Salmonella enteritidis (S. enteritidis) are common food-borne pathogens, which pose a very significant threat to the healthcare environment. The rapid detection of relevant bacteria can help control their rapid spread, while the traditional bacterial culture detection method is time-consuming and not conducive to the rapid detection of pathogens. Recently, new detection methods for related pathogenic bacteria have emerged, but these methods are relatively complex, and few methods can detect two bacteria at the same time. Therefore, there is an urgent need to develop multi-target, convenient, and fast pathogen detection methods. This method successfully constructed an enzyme-free fluorescent biosensor based on the adapter-mediated strand displacement reaction to detect E. coli ATCC25922 and S. enteritidis ATCC13076. This method had an ultrasensitive detection limit of 0.7 CFU/mL and 0.61 CFU/mL within 20 min, with a broad linear range of 34–105 CFU/mL of E. coli and 17–106 CFU/mL of S. enteritidis, respectively. Importantly, the spiked recovery of the three clinical fluid samples performed well, which proved that this method had the potential to detect E. coli and S. enteritidis in clinical samples. The sensor constructed by this method can detect dual targets at the same time, increasing the possibility of large-scale clinical use.

{"title":"Simultaneous detection of dual targets Escherichia coli and Salmonella enteritidis using enzyme-free strand displacement reaction","authors":"Shixin Yan,&nbsp;Yuling Xiao,&nbsp;Ruijuan Shen,&nbsp;Jiazhe Cheng,&nbsp;Yuling Zhang,&nbsp;Nan Wu,&nbsp;Jinhao Chen,&nbsp;Jie Chen,&nbsp;Peng Zhang,&nbsp;Jia Geng","doi":"10.1002/mba2.70002","DOIUrl":"https://doi.org/10.1002/mba2.70002","url":null,"abstract":"<p><i>Escherichia coli</i> (<i>E. coli</i>) and <i>Salmonella enteritidis</i> (<i>S. enteritidis</i>) are common food-borne pathogens, which pose a very significant threat to the healthcare environment. The rapid detection of relevant bacteria can help control their rapid spread, while the traditional bacterial culture detection method is time-consuming and not conducive to the rapid detection of pathogens. Recently, new detection methods for related pathogenic bacteria have emerged, but these methods are relatively complex, and few methods can detect two bacteria at the same time. Therefore, there is an urgent need to develop multi-target, convenient, and fast pathogen detection methods. This method successfully constructed an enzyme-free fluorescent biosensor based on the adapter-mediated strand displacement reaction to detect <i>E. coli</i> ATCC25922 and <i>S. enteritidis</i> ATCC13076. This method had an ultrasensitive detection limit of 0.7 CFU/mL and 0.61 CFU/mL within 20 min, with a broad linear range of 34–10<sup>5</sup> CFU/mL of <i>E. coli</i> and 17–10<sup>6</sup> CFU/mL of <i>S. enteritidis</i>, respectively. Importantly, the spiked recovery of the three clinical fluid samples performed well, which proved that this method had the potential to detect <i>E. coli</i> and <i>S. enteritidis</i> in clinical samples. The sensor constructed by this method can detect dual targets at the same time, increasing the possibility of large-scale clinical use.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143116705","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}
引用次数: 0
The potency of aloe emodin-loaded nanoparticles in conjunction with IFN-γ for the pretreatment of mesenchymal stem cells with class II transactivator silence to alleviate severe acute pancreatitis
Pub Date : 2025-01-09 DOI: 10.1002/mba2.70001
Yu Zou, Qin Qin, Xiaoshuang Song, Yuchuan Deng, Simeng Liu, Huimin Liu, Ailing Jiang, Mao Wang, Yiran Song, Dujiang Yang, Huimin Lu, Kun Jiang, Qian Yao, Yu Zheng

Mesenchymal stem cells (MSCs) have a moderate impact on the therapy of severe acute pancreatitis. This study seeks to improve the therapeutic effectiveness of MSCs. By preconditioning them via the upregulation of critical anti-inflammatory molecules, so diminishing immune rejection, we are creating a path for more effective treatments. Aloe emodin (AE), a natural active monomer with low-toxicity, in conjunction with interferon gamma (IFN-γ) (I-AE), markedly upregulated immunosuppressive molecules indoleamine 2,3-dioxygenase and programmed cell death-Ligand 1 in MSCs, thereby pharmacologically modulating the inhibition of CD4 − T cell activation in vitro effectively. Transient transfection of small interfering RNA silenced the class II transactivator (CIITA) gene expression of umbilical cord mesenchymal stem cells (UMSCs) interfering with human leukocyte antigen class II expression to avert immune rejection. AE-loaded nanoparticles efficiently maintained proliferation inhibition of MSCs within a manageable range by sustained release. UMSCs pretreated by I-AE with CIITA silencing preserved pancreatic structure as evidenced by diminished acinar cell death, reduced pancreatic edema and inflammation, and significantly lowered serum amylase levels The encouraging potential of UMSCs with CIITA gene silencing combined with AE and IFN-γ pretreatment offers optimism for clinical application in pancreatitis therapy.

{"title":"The potency of aloe emodin-loaded nanoparticles in conjunction with IFN-γ for the pretreatment of mesenchymal stem cells with class II transactivator silence to alleviate severe acute pancreatitis","authors":"Yu Zou,&nbsp;Qin Qin,&nbsp;Xiaoshuang Song,&nbsp;Yuchuan Deng,&nbsp;Simeng Liu,&nbsp;Huimin Liu,&nbsp;Ailing Jiang,&nbsp;Mao Wang,&nbsp;Yiran Song,&nbsp;Dujiang Yang,&nbsp;Huimin Lu,&nbsp;Kun Jiang,&nbsp;Qian Yao,&nbsp;Yu Zheng","doi":"10.1002/mba2.70001","DOIUrl":"https://doi.org/10.1002/mba2.70001","url":null,"abstract":"<p>Mesenchymal stem cells (MSCs) have a moderate impact on the therapy of severe acute pancreatitis. This study seeks to improve the therapeutic effectiveness of MSCs. By preconditioning them via the upregulation of critical anti-inflammatory molecules, so diminishing immune rejection, we are creating a path for more effective treatments. Aloe emodin (AE), a natural active monomer with low-toxicity, in conjunction with interferon gamma (IFN-γ) (I-AE), markedly upregulated immunosuppressive molecules indoleamine 2,3-dioxygenase and programmed cell death-Ligand 1 in MSCs, thereby pharmacologically modulating the inhibition of CD4 − T cell activation in vitro effectively. Transient transfection of small interfering RNA silenced the class II transactivator (CIITA) gene expression of umbilical cord mesenchymal stem cells (UMSCs) interfering with human leukocyte antigen class II expression to avert immune rejection. AE-loaded nanoparticles efficiently maintained proliferation inhibition of MSCs within a manageable range by sustained release. UMSCs pretreated by I-AE with CIITA silencing preserved pancreatic structure as evidenced by diminished acinar cell death, reduced pancreatic edema and inflammation, and significantly lowered serum amylase levels The encouraging potential of UMSCs with CIITA gene silencing combined with AE and IFN-γ pretreatment offers optimism for clinical application in pancreatitis therapy.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143113735","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}
引用次数: 0
A hydrogel miscible azelaic acid-ionic liquids for the treatment of acne vulgaris: Enhanced solubility and skin retention
Pub Date : 2025-01-02 DOI: 10.1002/mba2.70000
Zhezheng Fang, Xianzi Zheng, Yanyun Ma, Wei Wu, Yi Lu

Azelaic acid (AzA) is a natural dicarboxylic acid used to treat acne vulgaris but is greatly limited by poor aqueous solubility. This study aims to enhance the solubility and skin retention of AzA by ionic liquids (ILs). AzA-ILs were synthesized by a decomposition reaction with amine compounds. AzA-ILs synthesized with Tris-(hydroxymethyl)-aminomethane ([AzA][Tris]) and meglumine ([AzA][Meg]) at a molar ratio of 1:2 were liquid at room temperature and miscible with water. 1H-NMR and FT-IR confirmed the synthesis of AzA-ILs. [AzA][Tris] got higher transdermal transport and skin retention of AzA than [AzA][Meg]. ZEN has a lower viscosity and better spreadability than Carbomer and thus was adopted as the gel matrix. [AzA][Tris] was also miscible with the ZEN matrix at any concentration. Hydrogels containing 10% (w/w) AzA exhibited the highest transdermal transport and skin retention among hydrogels with higher or lower concentrations of AzA. AzA-IL hydrogel (10%, w/w) obtained similar therapeutic efficacy but lower skin irritation than the Finacea® (a marketed hydrogel of 15% AzA). In conclusion, ILs greatly enhanced the aqueous solubility of AzA to develop transparent hydrogel and skin retention to achieve good treatment for acne vulgaris.

{"title":"A hydrogel miscible azelaic acid-ionic liquids for the treatment of acne vulgaris: Enhanced solubility and skin retention","authors":"Zhezheng Fang,&nbsp;Xianzi Zheng,&nbsp;Yanyun Ma,&nbsp;Wei Wu,&nbsp;Yi Lu","doi":"10.1002/mba2.70000","DOIUrl":"https://doi.org/10.1002/mba2.70000","url":null,"abstract":"<p>Azelaic acid (AzA) is a natural dicarboxylic acid used to treat acne vulgaris but is greatly limited by poor aqueous solubility. This study aims to enhance the solubility and skin retention of AzA by ionic liquids (ILs). AzA-ILs were synthesized by a decomposition reaction with amine compounds. AzA-ILs synthesized with Tris-(hydroxymethyl)-aminomethane ([AzA][Tris]) and meglumine ([AzA][Meg]) at a molar ratio of 1:2 were liquid at room temperature and miscible with water. <sup>1</sup>H-NMR and FT-IR confirmed the synthesis of AzA-ILs. [AzA][Tris] got higher transdermal transport and skin retention of AzA than [AzA][Meg]. ZEN has a lower viscosity and better spreadability than Carbomer and thus was adopted as the gel matrix. [AzA][Tris] was also miscible with the ZEN matrix at any concentration. Hydrogels containing 10% (w/w) AzA exhibited the highest transdermal transport and skin retention among hydrogels with higher or lower concentrations of AzA. AzA-IL hydrogel (10%, w/w) obtained similar therapeutic efficacy but lower skin irritation than the Finacea® (a marketed hydrogel of 15% AzA). In conclusion, ILs greatly enhanced the aqueous solubility of AzA to develop transparent hydrogel and skin retention to achieve good treatment for acne vulgaris.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143110778","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}
引用次数: 0
Unwinding matters: WED domain determines Cas9 activity by accelerating DNA unwinding and R-loop formation 解绕问题:WED结构域通过加速DNA解绕和r环形成来决定Cas9的活性
Pub Date : 2024-12-19 DOI: 10.1002/mba2.107
Mei Luo, Shaohua Yao
<p>In a recent <i>Cell</i> paper,<span><sup>1</sup></span> Amy R. Eggers and colleagues from Jennifer A. Doudna's laboratory elucidated the mechanism by which an engineered CRISPR-Cas9 system significantly enhances editing efficiency by accelerating DNA unwinding and R-loop formation. The discovery and development of CRISPR-Cas9 gene editing technology have significantly revolutionized our ability to manipulate genomic sequences across a wide variety of species, as well as in clinical therapeutics. However, the efficiency of Cas9 proteins, especially the miniature ones, is generally low, requiring further improvement. In this article, the authors demonstrated that WED domain is a dominant determinant of target DNA unwinding and R-loop formation and its engineering improved genome-editing efficiency and expand PAM preference.</p><p>When binding to their target DNA sequences under the direction of PAM interaction and the guidance of single guide RNAs (sgRNA), Cas9 proteins separates the nontarget strand of the sgRNA from its target strand to form an R-loop structure. Subsequently, the cleavage activity domain of Cas9 cuts the DNA at this location, resulting in a double-strand break (Figure Fig 1). This process largely relies on the helicase activity of Cas9 to unwind the double-stranded target DNA into single strands for cutting. Evidence have shown that the formation of the R-loop is the rate-limiting step in this process.<span><sup>2</sup></span> Therefore, accelerating DNA unwinding and R-loop formation may be a potential strategy to improve CRISPR-Cas9 efficiency. Moreover, considering the size constraints imposed by certain delivery methods for in vivo applications, such as AAV, more compact Cas9 variants, including saCas9, cjCas9, and Nme2Cas9 have earned increasing interest. However, the activity of these editors generally lower than their larger orthologues, for example spCas9, which limited their applications.</p><p>In a previous study, the authors from the same lab evolved a Geobacillus stearothermophilus Cas9 (GeoCas9) using a bacterial double-plasmid selection system.<span><sup>3</sup></span> The resulting evolved iGeoCas9 exhibited more than one hundred-fold improvement in the editing of mammalian genomes. However, its molecular basis remains unclear. Through cryo-electron microscopy structural analysis, the current study found that the three amino acids mutations in the WED domain significantly enhance the electrostatic interactions between iGeoCas9 and the DNA strand. This alteration may facilitate the separation of DNA strands and the formation of the R-loop before cutting. Additionally, the PAM recognition preference of iGeoCas9 is more relaxed compared to that of WT-GeoCas9. One possible hypothesis is that the mutations in the WED domain alter its interactions with the DNA backbone, leading to nonnative PAM recognition and cutting activity. To test this hypothesis, the authors conducted enzymatic activity assays using several muta
将这一策略应用于另一种紧凑型Cas9--Nme2Cas9,结果发现iNme2Cas9具有加速DNA解旋和R环形成的活性,其基因编辑活性显著高于WT Nme2Cas9,与spCas9相当。WED结构域与目标dsDNA之间相互作用的增加明显加速了R环的形成,从而使Cas9在哺乳动物体内镁离子浓度较低的环境中有效发挥作用。此外,不同Cas9变体对WED结构域的类似修饰也能提高编辑效率。这一发现为人们深入了解Cas9的结构与功能关系提供了宝贵的视角,也为优化和设计更高效、更特异的基因编辑工具奠定了理论基础。未来研究的重点是进一步优化Cas9的其他功能,如增强其在各种环境中的稳定性,扩大其靶DNA序列范围。此外,整合其他基因编辑技术,如 CRISPR-Cas12a 或 CRISPR-Cas13,可进一步提高基因编辑的多样性和灵活性。然而,Cas9衍生的编辑器(如碱基编辑器和质粒编辑器)的活性与其内在活性密切相关,本实验中WED结构域的突变是否适用于其衍生编辑器,还有待进一步实验验证。姚少华指导并修改了手稿。所有作者均已阅读并批准最终稿件。作者声明无利益冲突。
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引用次数: 0
Biomimetic nanosystems based on cell membranes (BNCMs) for cancer immunotherapy 基于细胞膜的仿生纳米系统用于癌症免疫治疗
Pub Date : 2024-12-10 DOI: 10.1002/mba2.106
Yixi Wang, Xianzhou Huang, Qinjie Wu, Changyang Gong

With the development of nanosystems, they are gradually utilized to ameliorate diverse cancer therapies. Specifically for immunotherapy, most nanosystems are elaborately designed to initiate the self-sustaining “cancer immunity cycle (CIC)” to elicit the immune response. However, owing to the highly complex circulatory environment, nanosystems may face issues like nonspecific nanoparticle uptake and rapid clearance, leaving enormous room for advancement. For employing the biomimetic design in nanosystems, biomimetic nanosystems based on cell membranes (BNCMs) inherit various functional molecules from source cells, permitting precise tumor targeting, enhancing blood circulation, and conferring more desired functionality for a more robust immune response. To take full advantage of the BNCMs, understanding their functions in cancer immunotherapy is essential. In this review, the unique properties of BNCMs derived from various cells and main preparation strategies are introduced. Subsequently, the recent advances of BNCMs for improving cancer immunotherapy are discussed from the aspects of their roles in particular stages of the CIC, and the working mechanisms of the outer cell membranes are highlighted. Finally, along with the analysis of existing bottlenecks for clinical translation, some suggestions for the future development of BNCMs are put forward.

随着纳米系统的发展,它们逐渐被用于改善各种癌症治疗。特别是对于免疫治疗,大多数纳米系统被精心设计为启动自我维持的“癌症免疫周期(CIC)”来引发免疫反应。然而,由于高度复杂的循环环境,纳米系统可能面临诸如非特异性纳米颗粒摄取和快速清除等问题,留下了巨大的发展空间。在纳米系统中采用仿生设计,基于细胞膜的仿生纳米系统继承了来自源细胞的各种功能分子,允许精确的肿瘤靶向,增强血液循环,并赋予更理想的功能,以实现更强大的免疫反应。为了充分利用bcmm,了解它们在癌症免疫治疗中的功能至关重要。本文综述了来自不同细胞的bmcm的独特性质和主要制备策略。随后,从bmcm在CIC特定阶段的作用方面讨论了bmcm在改善肿瘤免疫治疗方面的最新进展,并重点介绍了外细胞膜的工作机制。最后,分析了临床翻译中存在的瓶颈,并对临床翻译的未来发展提出了建议。
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引用次数: 0
The osteogenic effect of mesenchymal stem cells regulated by photo-crosslinked hydrogels with tunable elastic modulus 弹性模量可调的光交联水凝胶调控间充质干细胞的成骨作用
Pub Date : 2024-12-03 DOI: 10.1002/mba2.105
Haifu Sun, Chen Qian, Kai Chen, Yu Wang, Yuqing Yang, Yonggang Li, Fan Xu, Liang Chen, Kun Li, Youzhi Hong, Yusen Qiao, Dechun Geng

Biomimicry is the enduring pursuit in the field of bone implants, wherein bio-materials with adjustable elastic modulus and porosity, the same as natural bone, offer a novel strategy for developing and applying new bone repair materials. Conventional biomaterials are often used to repair bone defects without complete consideration of structural and functional osseointegration, leading to interface repair failure. In this study, organic-inorganic interpenetrating network technology was employed using varying amounts of nano-hydroxyapatite (nHAP) and methacrylated gelatin (GelMA) and osteogenic growth peptide (OGP) to construct biomimetic bones with low, medium, and high nano-hydroxyapatite content (GelMA-c-OGP/nHAP). As the concentration of nano-hydroxyapatite increases, comprehensive evaluations of the biomimetic materials were conducted using osteogenic ability tests, Micro-CT scans, nanoindentation tests, and mechanical tests. The developed biomimetic structural material exhibits well-controlled mechanical properties. Compared to natural bone trabeculae, this biomimetic material not only maintains the organic and inorganic ratio of natural bone but also demonstrates exceptional mechanical load-bearing capabilities. Additionaly,this scaffold exhibits good porosity and mechanical properties. It enhances cell adhesion, integrates perfectly with bone tissue, and demonstrates excellent osteogenic ability both in vitro and in vivo. This study lays the foundation for constructing biomimetic scaffolds with adjustable mechanical properties, presenting high prospects for applications in the field of tissue engineering.

仿生学是骨植入物领域的长期追求,其中具有可调节弹性模量和孔隙度的生物材料与天然骨一样,为开发和应用新型骨修复材料提供了新的策略。传统的生物材料常用于骨缺损修复,未充分考虑骨的结构和功能整合,导致界面修复失败。在本研究中,采用有机-无机互穿网络技术,使用不同量的纳米羟基磷灰石(nHAP)和甲基丙烯酸明胶(GelMA)和成骨生长肽(OGP)构建低、中、高纳米羟基磷灰石含量(GelMA-c-OGP/nHAP)的仿生骨。随着纳米羟基磷灰石浓度的增加,通过成骨能力测试、Micro-CT扫描、纳米压痕测试和力学测试对仿生材料进行综合评估。所研制的仿生结构材料具有良好的力学性能控制。与天然骨小梁相比,这种仿生材料不仅保持了天然骨的有机和无机比例,而且表现出优异的机械承重能力。此外,该支架具有良好的孔隙率和力学性能。增强细胞黏附,与骨组织完美结合,在体外和体内均表现出优异的成骨能力。本研究为构建力学性能可调的仿生支架奠定了基础,在组织工程领域具有广阔的应用前景。
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引用次数: 0
Recent advances and perspectives of multifunctional nanogels in biomedical applications 多功能纳米凝胶在生物医学中的应用进展与展望
Pub Date : 2024-11-28 DOI: 10.1002/mba2.104
Bicheng Han, Zideng Dai, Hangrong Chen

Nanogels (NGs) are considered as a kind of nanoscale hydrogels (<200 nm) endowing with the functions of both nanomaterials and hydrogels. In the last 20 years, NGs have garnered significant attention due to their versatility and adaptability. Herein, a comprehensive overview of the latest advancements and current research status of NGs is provided, with a particular focus on the synthesis strategies involving physical and chemical cross-linking methods, as well as the advantages of NGs in drug loading and responsive release. Based on the diverse design strategies of NGs, four key biomedical applications, including inflammation therapy, regenerative medicine, bioimaging and tumor therapy are further summarized and discussed. Moreover, the existed inherent challenges facing NGs are proposed, while highlighting their potential to revolutionize therapeutic and diagnostic approaches. Finally, we look forward to the further development and promising potentials of NGs in biomedical applications. This review aims to serve as a valuable reference for researchers, providing some insights into the evolving landscape of NGs and their potential in advanced biomedical applications.

纳米凝胶(NGs)被认为是一种兼具纳米材料和水凝胶功能的纳米级水凝胶(< 200nm)。在过去的20年里,ngg因其多功能性和适应性而获得了极大的关注。本文综述了纳米颗粒的最新进展和研究现状,重点介绍了纳米颗粒的物理交联和化学交联合成策略,以及纳米颗粒在载药和反应释放方面的优势。基于NGs的多种设计策略,进一步总结和讨论了NGs在炎症治疗、再生医学、生物成像和肿瘤治疗等生物医学领域的四个关键应用。此外,本文还提出了纳米粒子所面临的固有挑战,同时强调了它们在彻底改变治疗和诊断方法方面的潜力。最后,展望了纳米粒子在生物医学领域的进一步发展和应用前景。本文综述旨在为研究人员提供有价值的参考,为纳米粒子的发展前景及其在先进生物医学应用中的潜力提供一些见解。
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引用次数: 0
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MedComm – Biomaterials and Applications
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