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, Yuan Zheng, Anxun Zhang, Jing Wang, Yao Xiao, 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}
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, Dinesh Harijan, Sunil Venkanna Pogu, Ganesan Prabusankar, 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}
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, Qiyue Xu, Jie Cai, Yiren Sun, Zhengjie Wang, 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}
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, Yuling Xiao, Ruijuan Shen, Jiazhe Cheng, Yuling Zhang, Nan Wu, Jinhao Chen, Jie Chen, Peng Zhang, 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}
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, 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","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}
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, Xianzi Zheng, Yanyun Ma, Wei Wu, 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}
<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
{"title":"Unwinding matters: WED domain determines Cas9 activity by accelerating DNA unwinding and R-loop formation","authors":"Mei Luo, Shaohua Yao","doi":"10.1002/mba2.107","DOIUrl":"https://doi.org/10.1002/mba2.107","url":null,"abstract":"<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","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868970","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}
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.
{"title":"Biomimetic nanosystems based on cell membranes (BNCMs) for cancer immunotherapy","authors":"Yixi Wang, Xianzhou Huang, Qinjie Wu, Changyang Gong","doi":"10.1002/mba2.106","DOIUrl":"https://doi.org/10.1002/mba2.106","url":null,"abstract":"<p>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.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860972","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}
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.
{"title":"The osteogenic effect of mesenchymal stem cells regulated by photo-crosslinked hydrogels with tunable elastic modulus","authors":"Haifu Sun, Chen Qian, Kai Chen, Yu Wang, Yuqing Yang, Yonggang Li, Fan Xu, Liang Chen, Kun Li, Youzhi Hong, Yusen Qiao, Dechun Geng","doi":"10.1002/mba2.105","DOIUrl":"https://doi.org/10.1002/mba2.105","url":null,"abstract":"<p>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.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763960","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}
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.
{"title":"Recent advances and perspectives of multifunctional nanogels in biomedical applications","authors":"Bicheng Han, Zideng Dai, Hangrong Chen","doi":"10.1002/mba2.104","DOIUrl":"https://doi.org/10.1002/mba2.104","url":null,"abstract":"<p>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.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749216","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}