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Lipid-based nanocarriers: an attractive approach for rheumatoid arthritis management 基于脂质的纳米载体:治疗类风湿性关节炎的一种极具吸引力的方法。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-01 DOI: 10.1039/D4BM01058B
Moataz B. Zewail, Ahmed S. Doghish, Hussein M. El-Husseiny, Eman A. Mady, Osama A. Mohammed, Abdullah M. M. Elbadry, Amir S. Elbokhomy, Abdelmenem Bhnsawy and Walaa A. El-Dakroury

Lipid nanoparticles (LNPs) have emerged as transformative tools in modern drug delivery, offering unparalleled potential in enhancing the efficacy and safety of various therapeutics. In the context of rheumatoid arthritis (RA), a disabling autoimmune disorder characterized by chronic inflammation, joint damage, and limited patient mobility, LNPs hold significant promise for revolutionizing treatment strategies. LNPs offer several advantages over traditional drug delivery systems, including improved pharmacokinetics, enhanced tissue penetration, and reduced systemic toxicity. This article concisely summarizes the pathogenesis of RA, its associated risk factors, and therapeutic techniques and their challenges. Additionally, it highlights the noteworthy advancements made in managing RA through LNPs, including liposomes, niosomes, bilosomes, cubosomes, spanlastics, ethosomes, solid lipid nanoparticles, lipid micelles, lipid nanocapsules, nanostructured lipid carriers, etc. It also delves into the specific functional attributes of these nanocarrier systems, focusing on their role in treating and monitoring RA.

脂质纳米粒子(LNPs)已成为现代给药领域的变革性工具,在提高各种疗法的疗效和安全性方面具有无与伦比的潜力。类风湿性关节炎(RA)是一种致残性自身免疫性疾病,其特点是慢性炎症、关节损伤和患者活动受限。与传统给药系统相比,LNPs 具有多种优势,包括改善药代动力学、增强组织渗透性和降低全身毒性。本文简要概述了 RA 的发病机制、相关风险因素、治疗技术及其挑战。此外,文章还重点介绍了在通过 LNPs(包括脂质体、niosomes、bilosomes、cubosomes、spanlastics、ethosomes、固体脂质纳米颗粒、脂质胶束、脂质纳米胶囊、纳米结构脂质载体等)治疗 RA 方面取得的显著进展。报告还深入探讨了这些纳米载体系统的具体功能属性,重点关注它们在治疗和监测 RA 方面的作用。
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引用次数: 0
Trends in protein derived materials for wound care applications 用于伤口护理的蛋白质衍生材料的发展趋势。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-01 DOI: 10.1039/D4BM01099J
Muhammad Zubair, Saadat Hussain, Mujeeb- ur-Rehman, Ajaz Hussain, Muhammad Ehtisham Akram, Sohail Shahzad, Zahid Rauf, Maria Mujahid and Aman Ullah

Natural resource based polymers, especially those derived from proteins, have attracted significant attention for their potential utilization in advanced wound care applications. Protein based wound care materials provide superior biocompatibility, biodegradability, and other functionalities compared to conventional dressings. The effectiveness of various fabrication techniques, such as electrospinning, phase separation, self-assembly, and ball milling, is examined in the context of developing protein-based materials for wound healing. These methods produce a wide range of forms, including hydrogels, scaffolds, sponges, films, and bioinspired nanomaterials, each designed for specific types of wounds and different stages of healing. This review presents a comprehensive analysis of recent research that investigates the transformation of proteins into materials for wound healing applications. Our focus is on essential proteins, such as keratin, collagen, gelatin, silk, zein, and albumin, and we emphasize their distinct traits and roles in wound care management. Protein-based wound care materials show promising potential in biomedical engineering, offering improved healing capabilities and reduced risks of infection. It is crucial to explore the potential use of these materials in clinical settings while also addressing the challenges that may arise from their commercialization in the future.

以自然资源为基础的聚合物,尤其是源自蛋白质的聚合物,因其在先进伤口护理应用中的潜在用途而备受关注。与传统敷料相比,基于蛋白质的伤口护理材料具有更好的生物相容性、生物可降解性和其他功能。在开发基于蛋白质的伤口愈合材料方面,我们研究了各种制造技术的有效性,如电纺丝、相分离、自组装和球磨。这些方法可以制造出多种形式的材料,包括水凝胶、支架、海绵、薄膜和生物启发纳米材料,每种材料都是针对特定类型的伤口和不同的愈合阶段而设计的。本综述全面分析了将蛋白质转化为伤口愈合材料的最新研究成果。我们的重点是基本蛋白质,如角蛋白、胶原蛋白、明胶、蚕丝、玉米蛋白和白蛋白,并强调它们在伤口护理管理中的独特特性和作用。以蛋白质为基础的伤口护理材料在生物医学工程中显示出巨大的潜力,可提高愈合能力并降低感染风险。关键是要探索这些材料在临床环境中的潜在用途,同时应对未来商业化过程中可能出现的挑战。
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引用次数: 0
GelMA/tannic acid hydrogel decorated polypropylene mesh facilitating regeneration of abdominal wall defects† GelMA/单宁酸水凝胶装饰聚丙烯网片促进腹壁缺损再生。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-10-31 DOI: 10.1039/D4BM01066C
Haonan Huang, Fuxin Tang, Wenchang Gan, Ruibing Li, Zehui Hou, Taicheng Zhou and Ning Ma

Polypropylene (PP) mesh is a widely used prosthetic material in hernia repair due to its excellent mechanical properties and appropriate biocompatibility. However, its application is limited due to severe adhesion between the mesh and the abdominal viscera, leading to complications such as chronic pain, intestinal obstruction, and hernia recurrence. Currently, building anti-adhesive PP mesh remains a formidable challenge. In this work, a novel anti-adhesive PP mesh (PPM/GelMA/TA) was designed with a simple and efficient in situ gel of GelMA solution on the surface of PP mesh and further crosslinking of tannic acid (TA). It was demonstrated that PPM/GelMA/TA has good biocompatibility and excellent antioxidant property and effectively activates the polarization of macrophages toward the M2 phenotype in vitro. In addition, PPM/GelMA/TA could inhibit the growth of bacteria, which is of great significance for preventing postoperative infections. Furthermore, in the repair of full-thickness abdominal wall defects in rats, PPM/GelMA/TA reduced inflammation, promoted macrophage M2 polarization, and collagen deposition and angiogenesis so that does not cause any abdominal adhesion compared with PP mesh. As a result, our PPM/GelMA/TA shows an attractive prospect in the treatment of abdominal wall defect without adhesions.

聚丙烯(PP)网片具有优良的机械性能和适当的生物相容性,是疝修补术中广泛使用的假体材料。然而,由于网片与腹腔内脏之间存在严重粘连,导致慢性疼痛、肠梗阻和疝气复发等并发症,其应用受到限制。目前,制造抗粘连 PP 网片仍是一项艰巨的挑战。本研究设计了一种新型防粘聚丙烯网(PPM/GelMA/TA),在聚丙烯网表面原位凝胶 GelMA 溶液,并进一步交联单宁酸(TA)。实验证明,PPM/GelMA/TA 具有良好的生物相容性和优异的抗氧化性,并能在体外有效激活巨噬细胞向 M2 表型极化。此外,PPM/GelMA/TA 还能抑制细菌生长,对预防术后感染具有重要意义。此外,在大鼠全厚腹壁缺损的修复中,PPM/GelMA/TA 可减少炎症反应,促进巨噬细胞 M2 极化,促进胶原沉积和血管生成,因此与 PP 网片相比不会造成任何腹腔粘连。因此,我们的 PPM/GelMA/TA 在治疗无粘连的腹壁缺损方面显示出诱人的前景。
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引用次数: 0
MicBall800-coated metal clip as a novel fluorescent marker for image-guided laparoscopic surgery† MicBall800 涂层金属夹作为图像引导腹腔镜手术的新型荧光标记。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-10-30 DOI: 10.1039/D4BM01252F
Hyoung-Jun Kim, Hong Man Yoon, Youngjeon Lee, Kyung Seob Lim, Jung Bae Seong, Sung-Jae Park and Yongdoo Choi

Accurate tumor localization is crucial for the success of minimally invasive surgery, as it minimizes the resection of normal tissues surrounding tumors. Traditional methods for marking gastrointestinal (GI) tumors, such as ink tattooing, intraoperative gastroscopy or colonoscopy, and placement of metal clips, have major drawbacks in their application in laparoscopic surgery. Therefore, the development of safe and easy-to-operate marking methods for accurate and real-time detection of GI tumors during laparoscopic surgery remains an ongoing challenge. Here, we propose a new fluorescent metal clip (MicBall800 clip) for noninvasive and precise fluorescence marking of GI tumors. First, we prepared a poly(methyl methacrylate) microball with small, multiple, and separated pores in its internal structure, and near-infrared fluorescence dye (IRDye800CW) and human serum albumin complex were loaded into the pores. This near-infrared-dye-loaded poly(methyl methacrylate) microball (MicBall800) was then coated onto the surface of the metal clips to produce a highly fluorescent MicBall800 clip. Safety and biocompatibility tests of the MicBall800 clip were conducted by the Korea Testing Certification Institute. The MicBall800 clip was evaluated in vivo using a porcine model. The MicBall800 clip passed safety and biocompatibility tests. The MicBall800 clip could be easily marked at the target sites without causing any side effects and was detected in real time during the laparoscopic operation. The data obtained from the safety and biocompatibility tests and the in vivo animal study indicate that the MicBall800 clip can be an important advancement in minimally invasive and precision surgery for GI cancers.

准确的肿瘤定位对微创手术的成功至关重要,因为它可以最大限度地减少对肿瘤周围正常组织的切除。传统的胃肠道(GI)肿瘤标记方法,如墨水纹身、术中胃镜或结肠镜检查、放置金属夹等,在腹腔镜手术中的应用存在很大缺陷。因此,开发安全、易于操作的标记方法,以便在腹腔镜手术中准确、实时地检测消化道肿瘤仍是一项持续的挑战。在此,我们提出了一种新型荧光金属夹(MicBall800 夹),用于对消化道肿瘤进行无创、精确的荧光标记。首先,我们制备了一种聚甲基丙烯酸甲酯微球,其内部结构具有小孔、多孔和分离孔,并在孔中装载了近红外荧光染料(IRDye800CW)和人血清白蛋白复合物。然后将这种负载了近红外染料的聚甲基丙烯酸甲酯微球(MicBall800)涂覆到金属夹的表面,制成高荧光的 MicBall800 夹。MicBall800 药夹的安全性和生物相容性测试由韩国测试认证院进行。MicBall800 夹使用猪模型进行了体内评估。MicBall800 夹通过了安全性和生物相容性测试。MicBall800 夹很容易标记目标部位,不会产生任何副作用,并能在腹腔镜手术过程中被实时检测到。从安全性和生物相容性测试以及体内动物实验中获得的数据表明,MicBall800 夹可以成为消化道癌症微创精准手术的重要进展。
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引用次数: 0
Construction of 3D tumor in vitro models with an immune microenvironment exhibiting similar tumor properties and biomimetic physiological functionality 构建具有免疫微环境的三维肿瘤体外模型,展现类似的肿瘤特性和生物模拟生理功能。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-10-30 DOI: 10.1039/D4BM00754A
Yuhong Jiang, Lijuan Jin, Wenyu Liu, Hui Liu, Xiao Liu and Zhikai Tan

Tumors pose a serious threat to people's lives and health, and the complex tumor microenvironment is the biggest obstacle to their treatment. In contrast to the basic protein matrices typically employed in 2D or 3D cell culture systems, decellularized extracellular matrix (dECM) can create complex microenvironments. In this study, a combination of physicochemical methods was established to obtain liver decellularized extracellular matrix scaffolds (dLECMs) to provide mechanical support and cell adhesion sites. By co-culturing tumor cells, tumor-associated stromal cells and immune cells, an in vitro 3D tumor model with a biomimetic immune microenvironment was constructed. By utilizing microenvironment data obtained from human liver tumor tissues and refining the double seeding modeling process, 3D in vitro liver tumor-like tissues with a tumor immune microenvironment (TIME) were obtained and designated as reconstructed human liver cancer (RHLC). These tissues demonstrated similar tumor characteristics and exhibited satisfactory physiological functionality. The results of metabolic characterisation and mouse tumorigenicity testing verified that the constructed RHLC significantly increased in vitro drug resistance while also closely mimicking in vivo tissue metabolism. This opens up new possibilities for creating effective in vitro models for screening chemotherapy drugs.

肿瘤严重威胁着人们的生命和健康,而复杂的肿瘤微环境是治疗肿瘤的最大障碍。与二维或三维细胞培养系统通常采用的基本蛋白基质不同,脱细胞细胞外基质(dECM)可以创造复杂的微环境。本研究结合多种物理化学方法获得了肝脏脱细胞细胞外基质支架(dLECMs),以提供机械支撑和细胞粘附位点。通过共培养肿瘤细胞、肿瘤相关基质细胞和免疫细胞,构建了具有仿生免疫微环境的体外三维肿瘤模型。通过利用从人类肝脏肿瘤组织中获得的微环境数据并改进双种子建模过程,获得了具有肿瘤免疫微环境(TIME)的三维体外肝脏肿瘤样组织,并将其命名为重建人类肝癌(RHLC)。这些组织具有相似的肿瘤特征,并表现出令人满意的生理功能。代谢表征和小鼠致瘤性测试结果证实,构建的 RHLC 显著提高了体外抗药性,同时也密切模拟了体内组织代谢。这为创建用于筛选化疗药物的有效体外模型提供了新的可能性。
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引用次数: 0
Multifaceted role of nanocomposite hydrogels in diabetic wound healing: enhanced biomedical applications and detailed molecular mechanisms 纳米复合水凝胶在糖尿病伤口愈合中的多方面作用:增强的生物医学应用和详细的分子机制。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-10-30 DOI: 10.1039/D4BM01088D
Gege Xiong, Qiwei Chen, Qiuyu Wang, Xiaoxue Wang, Yaomu Xiao, Liuli Jin, Kaichong Yan, Xueyang Zhang and Fei Hu

The complex microenvironment of diabetic wounds, which is characterized by persistent hyperglycemia, excessive inflammatory responses, and hypoxic conditions, significantly impedes the efficacy of traditional hydrogels. Nanocomposite hydrogels, which combine the high-water content and biocompatibility of hydrogels with the unique functionalities of nanomaterials, offer a promising solution. These hydrogels exhibit enhanced antibacterial, antioxidant, and drug-release properties. Incorporating nanomaterials increases the mechanical strength and bioactivity of hydrogels, allowing for dynamic regulation of the wound microenvironment and promoting cell migration, proliferation, and angiogenesis, thereby accelerating wound healing. This review provides a comprehensive overview of the latest advances in nanocomposite hydrogels for diabetic wound treatment and discusses their advantages and molecular mechanisms at various healing stages. The study aims to provide a theoretical foundation and practical guidance for future research and clinical applications. Furthermore, it highlights the challenges related to the mechanical durability, antimicrobial performance, resistance issues, and interactions with the cellular environments of these hydrogels. Future directions include optimizing smart drug delivery systems and personalized medical approaches to enhance the clinical applicability of nanocomposite hydrogels.

糖尿病伤口微环境复杂,具有持续高血糖、过度炎症反应和缺氧等特点,这大大阻碍了传统水凝胶的功效。纳米复合水凝胶将水凝胶的高含水量和生物相容性与纳米材料的独特功能性结合在一起,提供了一种前景广阔的解决方案。这些水凝胶具有更强的抗菌、抗氧化和药物释放特性。加入纳米材料可提高水凝胶的机械强度和生物活性,对伤口微环境进行动态调节,促进细胞迁移、增殖和血管生成,从而加速伤口愈合。本综述全面概述了用于糖尿病伤口治疗的纳米复合水凝胶的最新进展,并讨论了其在不同愈合阶段的优势和分子机制。研究旨在为未来的研究和临床应用提供理论基础和实践指导。此外,它还强调了与这些水凝胶的机械耐久性、抗菌性能、抗药性问题以及与细胞环境的相互作用有关的挑战。未来的方向包括优化智能给药系统和个性化医疗方法,以提高纳米复合水凝胶的临床适用性。
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引用次数: 0
Recent advances in carrier-free natural small molecule self-assembly for drug delivery 用于给药的无载体天然小分子自组装的最新进展。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-10-30 DOI: 10.1039/D4BM01153H
Yehua Sun, Changyang Lei, Renzhong Qiao and Chao Li

Natural small-molecule drugs have been used for thousands of years for the prevention and treatment of human diseases. Most of the natural products available on the market have been modified into various polymer materials for improving the solubility, stability, and targeted delivery of drugs. However, these nanomedicines formed based on polymer carriers would produce severe problems such as systemic toxicity and kidney metabolic stress. In contrast, the carrier-free nanomedicines formed by their self-assembly in water have inherent advantages such as low toxicity, good biocompatibility, and biodegradability. This review summarizes the assembly process and application of natural small-molecule products, which are mainly driven by multiple non-covalent interactions, and includes single-molecule assembly, bimolecular assembly, drug-modified assembly, and organogels. Meanwhile, the molecular mechanism involved in different self-assembly processes is also discussed. Self-assembly simulation and structural modification of natural small-molecule products or traditional Chinese medicine molecules using molecular dynamics simulation and computer-assisted methods are proposed, which will lead to the discovery of more carrier-free nanomedicine drug delivery systems. Overall, this review provides an important understanding and strategy to study single-molecule and multi-molecule carrier-free nanomedicines.

几千年来,天然小分子药物一直被用于预防和治疗人类疾病。市场上的大多数天然产品都被改性为各种聚合物材料,以提高药物的溶解性、稳定性和靶向性。然而,这些基于聚合物载体形成的纳米药物会产生严重的问题,如全身毒性和肾脏代谢压力。相比之下,在水中自组装形成的无载体纳米药物具有毒性低、生物相容性好和可生物降解等固有优势。本综述总结了天然小分子产物的组装过程和应用,主要由多种非共价相互作用驱动,包括单分子组装、双分子组装、药物修饰组装和有机凝胶。同时,还讨论了不同自组装过程所涉及的分子机理。提出利用分子动力学模拟和计算机辅助方法对天然小分子产物或中药分子进行自组装模拟和结构修饰,从而发现更多的无载体纳米药物递送系统。总之,这篇综述为研究单分子和多分子无载体纳米药物提供了重要的认识和策略。
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引用次数: 0
Formulation of lipid nanoparticles containing ginsenoside Rg2 and protopanaxadiol for highly efficient delivery of mRNA† 含有人参皂苷 Rg2 和原人参皂苷的脂质纳米颗粒的配方,用于高效传递 mRNA。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-10-29 DOI: 10.1039/D4BM01070A
Sin A Park, Dajeong Hwang, Jae Hoon Kim, Seung-Yeul Lee, Jaebeom Lee, Han Sang Kim, Kyung-A Kim, Bumhee Lim, Jae-Eon Lee, Yong Hyun Jeon, Tae Jeong Oh, Jaewook Lee and Sungwhan An

Lipid nanoparticles (LNPs) are widely recognized as crucial carriers of mRNA in therapeutic and vaccine development. The typical lipid composition of mRNA-LNP systems includes an ionizable lipid, a helper lipid, a polyethylene glycol (PEG)-lipid, and cholesterol. Concerns arise regarding cholesterol's susceptibility to oxidation, potentially leading to undesired immunological responses and toxicity. In this study, we formulated novel LNPs by replacing cholesterol with phytochemical-derived compounds, specifically ginsenoside Rg2 and its derivative phytosterol protopanaxadiol (PPD), and validated their efficacy as mRNA delivery systems. The mRNA–LNP complexes were manually prepared through a simple mixing process. The biocompatibility of these Rg2-based LNPs (Rg2-LNP) and PPD-based LNPs (PPD-LNP) was assessed through cell viability assays, while the protective function of LNPs for mRNA was demonstrated by RNase treatment. Enhanced green fluorescent protein (EGFP) mRNA delivery and expression in A549 and HeLa cells were analyzed using optical microscopy and flow cytometry. The expression efficiency of Rg2-LNP and PPD-LNP was compared with that of commercially available LNPs, with both novel formulations demonstrating superior transfection and EGFP expression. Furthermore, in vivo tests following intramuscular (I.M.) injection in hairless mice demonstrated efficient luciferase (Luc) mRNA delivery and effective Luc expression using Rg2-LNP and PPD-LNP compared to commercial LNPs. Results indicated that the efficiency of EGFP and Luc expression in Rg2-LNP and PPD-LNP surpassed that of the cholesterol-based LNP formulation. These findings suggest that Rg2-LNP and PPD-LNP are promising candidates for future drug and gene delivery systems.

脂质纳米颗粒(LNPs)被广泛认为是治疗和疫苗开发中 mRNA 的重要载体。mRNA-LNP 系统的典型脂质成分包括可电离脂质、辅助脂质、聚乙二醇 (PEG) 脂质和胆固醇。胆固醇易被氧化,可能会导致不良的免疫反应和毒性,这引起了人们的关注。在这项研究中,我们用植物化学衍生化合物(特别是人参皂苷 Rg2 及其衍生物植物甾醇原人参皂苷(PPD))取代胆固醇,配制出新型 LNPs,并验证了它们作为 mRNA 递送系统的功效。mRNA-LNP 复合物是通过简单的混合过程手工制备的。通过细胞活力测定评估了这些基于 Rg2 的 LNPs(Rg2-LNP)和基于 PPD 的 LNPs(PPD-LNP)的生物相容性,同时通过 RNase 处理证明了 LNPs 对 mRNA 的保护功能。利用光学显微镜和流式细胞术分析了增强型绿色荧光蛋白(EGFP)mRNA在A549和HeLa细胞中的传递和表达情况。将 Rg2-LNP 和 PPD-LNP 的表达效率与市售 LNPs 的表达效率进行了比较,结果表明这两种新型制剂在转染和 EGFP 表达方面都更胜一筹。此外,在无毛小鼠肌肉注射后进行的体内测试表明,与市售 LNPs 相比,Rg2-LNP 和 PPD-LNP 能高效递送荧光素酶 (Luc) mRNA 并有效表达 Luc。结果表明,Rg2-LNP 和 PPD-LNP 中 EGFP 和 Luc 的表达效率超过了基于胆固醇的 LNP 制剂。这些研究结果表明,Rg2-LNP 和 PPD-LNP 有希望成为未来药物和基因递送系统的候选材料。
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引用次数: 0
Correction: Tobramycin-mediated self-assembly of DNA nanostructures for targeted treatment of Pseudomonas aeruginosa-infected lung inflammation 更正:托布霉素介导的 DNA 纳米结构自组装用于靶向治疗铜绿假单胞菌感染的肺部炎症。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-10-29 DOI: 10.1039/D4BM90084G
Yuhang Xu, Qian Liu, Bin Wang, Quan Li, Yue Chen, Yao Yang, Zhihao Zhu, Daohui Gong, Chuan Zhang, Guansong Wang and Hang Qian

Correction for ‘Tobramycin-mediated self-assembly of DNA nanostructures for targeted treatment of Pseudomonas aeruginosa-infected lung inflammation’ by Yuhang Xu et al., Biomater. Sci., 2024, 12, 2331–2340, https://doi.org/10.1039/D3BM02121A.

对 Yuhang Xu 等人的 "Tobramycin-mediated self-assembly of DNA nanostructures for targeted treatment of Pseudomonas aeruginosaed-infected lung inflammation "的更正,Biomater.Sci.,2024,12,2331-2340,https://doi.org/10.1039/D3BM02121A。
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引用次数: 0
Amplified response of drug-induced liver fibrosis via immune cell co-culture in a 3D in vitro hepatic fibrosis model† 在三维体外肝纤维化模型中通过免疫细胞共培养增强药物诱导的肝纤维化反应。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-10-29 DOI: 10.1039/D4BM00874J
Hyewon Jung, Mi-lang Kyun, Ji-In Kwon, Jeongha Kim, Ju-Kang Kim, Daeui Park, Yu Bin Lee and Kyoung-Sik Moon

Liver fibrosis, a critical consequence of chronic liver diseases, is characterized by excessive extracellular matrix (ECM) deposition driven by inflammation. This process involves complex interactions among hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells, the liver's resident macrophages. Kupffer cells are essential in initiating fibrosis through the release of pro-inflammatory cytokines that activate HSCs. Although various in vitro liver fibrosis models have been developed, there is a lack of models that include the immune environment of the liver to clarify the influence of immune cells on the progression of liver fibrosis. We developed an in vitro liver fibrosis model by co-culturing hepatocytes (HepaRG), a hepatic stellate cell line (LX-2), and macrophages (differentiated THP-1). The effects of liver fibrosis inducers, transforming growth factor-beta1 (TGF-β1) and methotrexate (MTX), on the inflammatory response and stellate cell activation were evaluated in this triple co-culture model. A triple co-culture condition was developed as a 3D in vitro model using gelatin methacrylate (GelMA), offering a more biomimetic environment and achieving liver fibrosis via immune cell activation associated ECM deposition. In this study, the developed triple co-culture model has the potential to elucidate cell progression roles in liver fibrosis and can be applied in drug screening and toxicity assessments targeting liver fibrosis.

肝纤维化是慢性肝病的一个重要后果,其特点是炎症导致细胞外基质(ECM)过度沉积。这一过程涉及肝细胞、肝星状细胞(HSCs)和Kupffer细胞(肝脏的常驻巨噬细胞)之间复杂的相互作用。Kupffer 细胞通过释放激活造血干细胞的促炎症细胞因子,对启动肝纤维化至关重要。虽然已经开发出了各种体外肝纤维化模型,但还缺乏包含肝脏免疫环境的模型来阐明免疫细胞对肝纤维化进展的影响。我们通过共培养肝细胞(HepaRG)、肝星状细胞系(LX-2)和巨噬细胞(分化的 THP-1)建立了体外肝纤维化模型。在这种三重共培养模型中,评估了肝纤维化诱导剂、转化生长因子-β1(TGF-β1)和甲氨蝶呤(MTX)对炎症反应和星状细胞活化的影响。利用甲基丙烯酸明胶(GelMA)开发了一种三重共培养条件的三维体外模型,提供了一种更仿生的环境,并通过与 ECM 沉积相关的免疫细胞活化实现肝纤维化。在这项研究中,所开发的三重共培养模型有望阐明细胞在肝纤维化中的作用,并可应用于针对肝纤维化的药物筛选和毒性评估。
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引用次数: 0
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