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Engineering considerations in the design of tissue specific bioink for 3D bioprinting applications. 三维生物打印应用中组织特异性生物墨水设计的工程考虑因素。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-13 DOI: 10.1039/d4bm01192a
Shivi Tripathi, Madhusmita Dash, Ruchira Chakraborty, Harri Junaedi Lukman, Prasoon Kumar, Shabir Hassan, Hassan Mehboob, Harpreet Singh, Himansu Sekhar Nanda

Over eight million surgical procedures are conducted annually in the United Stats to address organ failure or tissue losses. In response to this pressing need, recent medical advancements have significantly improved patient outcomes, primarily through innovative reconstructive surgeries utilizing tissue grafting techniques. Despite tremendous efforts, repairing damaged tissues remains a major clinical challenge for bioengineers and clinicians. 3D bioprinting is an additive manufacturing technique that holds significant promise for creating intricately detailed constructs of tissues, thereby bridging the gap between engineered and actual tissue constructs. In contrast to non-biological printing, 3D bioprinting introduces added intricacies, including considerations for material selection, cell types, growth, and differentiation factors. However, technical challenges arise, particularly concerning the delicate nature of living cells in bioink for tissue construction and limited knowledge about the cell fate processes in such a complex biomechanical environment. A bioink must have appropriate viscoelastic and rheological properties to mimic the native tissue microenvironment and attain desired biomechanical properties. Hence, the properties of bioink play a vital role in the success of 3D bioprinted substitutes. This review comprehensively delves into the scientific aspects of tissue-centric or tissue-specific bioinks and sheds light on the current challenges of the translation of bioinks and bioprinting.

在美国,每年有 800 多万例外科手术是为了解决器官衰竭或组织缺失问题。为了满足这一迫切需求,最近的医学进步显著改善了患者的治疗效果,主要是通过利用组织移植技术进行创新性重建手术。尽管付出了巨大努力,修复受损组织仍然是生物工程师和临床医生面临的一大临床挑战。三维生物打印是一种增材制造技术,有望制造出复杂精细的组织结构,从而缩小工程组织和实际组织结构之间的差距。与非生物打印相比,三维生物打印引入了更多复杂因素,包括材料选择、细胞类型、生长和分化因子等方面的考虑。然而,技术上的挑战也随之而来,特别是生物墨水中用于组织构建的活细胞的微妙性质,以及在如此复杂的生物力学环境中对细胞命运过程的有限了解。生物墨水必须具有适当的粘弹性和流变学特性,以模拟原生组织的微环境并获得理想的生物力学特性。因此,生物墨水的特性对三维生物打印替代品的成功起着至关重要的作用。本综述全面探讨了以组织为中心或组织特异性生物墨水的科学方面,并揭示了当前生物墨水和生物打印转化所面临的挑战。
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引用次数: 0
Co-assembled biomimetic fibrils from collagen and chitosan for performance-enhancing hemostatic dressing. 胶原蛋白和壳聚糖共组装生物仿生纤维,用于增强止血敷料的性能。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-12 DOI: 10.1039/d4bm01211a
Xingling Zeng, Zhaohui Sun, Lidan Chen, Xiaoxia Zhang, Xin Guo, Guoying Li

The development of safe and efficient hemostatic materials is medically important to prevent death due to trauma bleeding. Exploiting the synergistic effect between the D-periodic functional domain of collagen fibrils on platelet activation and cationic chitosan on erythrocyte aggregation is expected to develop performance-enhanced hemostatic materials. In this study, we prepared collagen fibrils and chitosan composite hemostatic materials by modulating the self-assembled bionic fibrillation of collagen with different degrees of deacetylation (DD, 50%, 70% and 85%) of chitosan. The findings indicated that chitosan promoted collagen self-assembly, with all the collagen fibrils demonstrating a typical D-periodical structure similar to that of the native collagen. Furthermore, the composite demonstrated enhanced structural integrity and procoagulant capacity along with good biocompatibility. Notably, the fibrillar composites with 70% DD of chitosan exhibited optimal mechanical properties, procoagulant activity, and adhesion of erythrocytes and platelets. Compared to pure collagen fibrils and the commercial hemostatic agent Celox™, the collagen/chitosan fibrillar composite treatment significantly accelerated hemostasis in the rat tail amputation model and liver injury model. This research offers new insights into the development of hemostatic materials and indicates that collagen-chitosan composites hold promising potential for clinical applications.

开发安全高效的止血材料对于防止创伤出血导致的死亡具有重要的医学意义。利用胶原纤维的 D 周期功能域对血小板活化和阳离子壳聚糖对红细胞聚集的协同作用,有望开发出性能更强的止血材料。在这项研究中,我们通过调节胶原蛋白的自组装仿生纤维化与壳聚糖的不同脱乙酰度(DD、50%、70%和85%),制备了胶原纤维和壳聚糖复合止血材料。研究结果表明,壳聚糖促进了胶原蛋白的自组装,所有胶原蛋白纤维都呈现出典型的 D 周期结构,与原生胶原蛋白相似。此外,复合材料的结构完整性和促凝能力都得到了增强,同时还具有良好的生物相容性。值得注意的是,壳聚糖含量为 70% DD 的纤维状复合材料具有最佳的机械性能、促凝活性以及对红细胞和血小板的粘附性。与纯胶原纤维和商用止血剂 Celox™ 相比,胶原蛋白/壳聚糖纤维状复合材料能显著加快大鼠断尾模型和肝损伤模型的止血速度。这项研究为止血材料的开发提供了新的见解,并表明胶原蛋白-壳聚糖复合材料在临床应用方面具有广阔的前景。
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引用次数: 0
Photoinitiator-free light-mediated crosslinking of dynamic polymer and pristine protein networks. 无光引发剂的光介导动态聚合物和原始蛋白质网络交联。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-12 DOI: 10.1039/d4bm00849a
Riccardo Rizzo, Dylan M Barber, Jackson K Wilt, Alexander J Ainscough, Jennifer A Lewis

Light-based patterning of synthetic and biological hydrogels enables precise spatial and temporal control over the formation of chemical bonds. However, photoinitiators are typically used to generate free radicals, which are detrimental to human cells. Here, we report a photoinitiator- and radical-free method based on ortho-nitrobenzyl alcohol (oNBA) photolysis, which gives rise to highly reactive nitroso and benzaldehyde groups. Synthetic hydrogel and pristine protein networks can rapidly form in the presence of these photo-generated reactive species. Thiol -oNBA bonds yield dynamic hydrogel networks (DHNs) via N-semimercaptal linkages that exhibit thixotropy, stress relaxation, and on-demand reversible gel-to-liquid transitions, while amine-oNBA bonds can be exploited to crosslink pristine proteins, such as gelatin and fibrinogen, by targeting their primary amines. Since this approach does not require incorporation of photoreactive moieties along the backbone, the resulting crosslinked proteins are well suited for bioadhesives. Our photoinitiator-free platform provides a versatile approach for rapidly creating synthetic and biological hydrogels for applications ranging from tissue engineering to biomedical devices.

通过光对合成和生物水凝胶进行图案化处理,可对化学键的形成进行精确的空间和时间控制。然而,光引发剂通常会产生对人体细胞有害的自由基。在这里,我们报告了一种基于正硝基苄醇 (oNBA) 光解的无光引发剂和自由基方法,这种方法会产生高活性的亚硝基和苯甲醛基团。合成水凝胶和原始蛋白质网络可在这些光产生的反应物存在下迅速形成。硫醇-oNBA 键通过 N-半巯基连接产生动态水凝胶网络 (DHN),这种网络具有触变性、应力松弛和按需可逆的凝胶-液体转变。由于这种方法不需要在骨架上加入光活性分子,因此交联后的蛋白质非常适合用于生物粘合剂。我们的无光引发剂平台为快速制造合成和生物水凝胶提供了一种多功能方法,其应用范围从组织工程到生物医学设备。
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引用次数: 0
Rapid neurostimulation at the micron scale with an optically controlled thermal-capture technique. 利用光学控制热捕捉技术在微米尺度上进行快速神经刺激。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-12 DOI: 10.1039/d4bm01114g
Alexey M Romshin, Nikolay A Aseyev, Olga S Idzhilova, Alena A Koryagina, Vadim E Zeeb, Igor I Vlasov, Pavel M Balaban

Precise control of cellular temperature at the microscale is crucial for developing novel neurostimulation techniques. Here, the effect of local heat on the electrophysiological properties of primary neuronal cultures and HEK293 cells at the subcellular level using a cutting-edge micrometer-scale thermal probe, the diamond heater-thermometer (DHT), is studied. A new mode of local heat action on a living cell, thermal-capture mode (TCM), is discovered using the DHT probe. In TCM, the application of a 50 °C temperature step induces a great increase in cellular response, allowing the cell to be thermally captured and depolarized by up to 20 mV. This thermal effect is attributed to local phase changes in the phospholipid membrane, enabling precise and reproducible modulation of cell activity. The TCM is shown to open up new opportunities for thermal cell stimulation. DHT reliably triggers action potentials (APs) in neurons at rates up to 30 Hz, demonstrating the ability to control cell excitability with millisecond and sub-millisecond resolution. AP shape is modulated by local heat as well. The ability to precisely control the AP shape and rate via thermal-capture mode opens new avenues for non-invasive, localized neurostimulation techniques, particularly in controlling neuron excitability.

在微米尺度上精确控制细胞温度对于开发新型神经刺激技术至关重要。本文利用最先进的微米级热探针--金刚石加热器温度计(DHT),研究了局部热量在亚细胞水平上对原代神经元培养物和 HEK293 细胞电生理特性的影响。利用 DHT 探针发现了活细胞局部热作用的新模式--热捕获模式(TCM)。在热捕获模式中,50 °C的温度阶跃会引起细胞反应的显著增加,使细胞被热捕获并去极化高达20 mV。这种热效应可归因于磷脂膜的局部相变,从而实现对细胞活性的精确、可重复的调节。中药为热刺激细胞带来了新的机遇。DHT 能以高达 30 Hz 的速率可靠地触发神经元中的动作电位(AP),证明了以毫秒级和亚毫秒级分辨率控制细胞兴奋性的能力。AP 的形状也受局部热量的调节。通过热捕获模式精确控制 AP 形状和速率的能力为非侵入性局部神经刺激技术,尤其是控制神经元兴奋性开辟了新的途径。
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引用次数: 0
Self-assembled carrier-free formulations based on medicinal and food active ingredients. 基于药用和食品活性成分的自组装无载体配方。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 DOI: 10.1039/d4bm00893f
Yuan Hao, Haixia Ji, Li Gao, Zhican Qu, Yinghu Zhao, Jiahui Chen, Xintao Wang, Xiaokai Ma, Guangyu Zhang, Taotao Zhang

The popularity of medicinal plants, which have a unique system and are mostly used in compound form for the prevention and treatment of a wide range of diseases, is growing worldwide. In recent years, with advances in chemical separation and structural analysis techniques, many of the major bioactive molecules of medicinal plants have been identified. However, the active ingredients in medicinal plants often possess chemical characteristics, including poor water solubility, stability and bioavailability, which limit their therapeutic applications. To address this problem, self-assembly of small molecules from medicinal food sources provides a new strategy. Driven by various types of acting forces, medicinal small molecules with modifiable groups, multiple sites of action, hydrophobic side chains, and rigid backbones with self-assembly properties are able to form various supramolecular network hydrogels, nanoparticles, micelles, and other self-assemblies. This review first summarizes the forms of self-assemblies such as supramolecular network hydrogels, nanoparticles, and micelles at the level of the action site, and discusses the recent studies on the active ingredients in medicinal plants that can be used for self-assembly, in addition to summarizing the advantages of self-assemblies for a variety of disease applications, including wound healing, antitumor, anticancer, and diabetes mellitus. Finally, the problems of self-assemblers and the possible directions for future development are presented. We firmly believe that self-assemblers have the potential to develop effective compounds from drug-food homologous plants, providing valuable information for drug research and new strategies and perspectives for the modernization of Chinese medicine.

药用植物具有独特的体系,大多以复方形式用于预防和治疗多种疾病,因此在全球范围内越来越受欢迎。近年来,随着化学分离和结构分析技术的进步,许多药用植物的主要生物活性分子已被鉴定出来。然而,药用植物中的活性成分往往具有化学特性,包括水溶性差、稳定性差和生物利用率低,从而限制了其治疗应用。为解决这一问题,从药用食物来源中自组装小分子提供了一种新策略。在各种作用力的驱动下,具有可修饰基团、多作用位点、疏水侧链和具有自组装特性的刚性骨架的药用小分子能够形成各种超分子网络水凝胶、纳米颗粒、胶束和其他自组装物。这篇综述首先从作用位点层面总结了超分子网络水凝胶、纳米颗粒、胶束等自组装形式,并讨论了近年来关于药用植物中可用于自组装的活性成分的研究,此外还总结了自组装在伤口愈合、抗肿瘤、抗癌、糖尿病等多种疾病应用中的优势。最后,介绍了自组装器存在的问题以及未来可能的发展方向。我们坚信,自组装技术有可能从药食同源植物中开发出有效的化合物,为药物研究提供有价值的信息,为中药现代化提供新的策略和前景。
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引用次数: 0
Three-dimensional structured PLCL/ADM bioactive aerogel for rapid repair of full-thickness skin defects. 用于快速修复全厚皮肤缺损的三维结构 PLCL/ADM 生物活性气凝胶。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 DOI: 10.1039/d4bm01214c
Xuchao Ning, Runjia Wang, Na Liu, Yong You, Yawen Wang, Jing Wang, Yuanfei Wang, Zhenyu Chen, Haiguang Zhao, Tong Wu

The failure to treat deep skin wounds can result in significant complications, and the limitations of current clinical treatments highlight the pressing need for the development of new deep wound healing materials. In this study, a series of three-dimensional structured PLCL/ADM composite aerogels were fabricated by electrospinning and subsequently characterized for their microstructure, compression mechanics, exudate absorption, and hemostatic properties. Additionally, the growth of HSFs and HUVECs, which are involved in wound repair, was observed in the aerogels. The composite aerogel was subsequently employed in wound repair experiments on rat full-thickness skin with the objective of observing the wound healing rate and examining histological utilizing H&E, Masson, CD31, and COL-I staining. The findings indicated that the PLCL/ADM composite aerogel with a 10% concentration exhibited uniform pore size distribution, a good three-dimensional structure, and compression properties comparable to those of human skin, which could effectively absorb exudate and exert hemostatic effect. In vivo experiment results demonstrated that the aerogel exhibited superior efficacy to conventional oil-gauze overlay therapy and ADM aerogel in promoting wound healing and could facilitate rapid, high-quality in situ repair of deep wounds, thereby offering a novel approach for skin tissue engineering and clinical wound treatment.

皮肤深层伤口治疗失败会导致严重的并发症,而目前临床治疗方法的局限性凸显了开发新型深层伤口愈合材料的迫切需要。本研究通过电纺丝技术制备了一系列三维结构的 PLCL/ADM 复合气凝胶,并对其微观结构、压缩力学、渗出物吸收和止血性能进行了表征。此外,在气凝胶中还观察到了参与伤口修复的 HSFs 和 HUVECs 的生长。随后,将复合气凝胶用于大鼠全厚皮肤的伤口修复实验,目的是观察伤口愈合率,并利用 H&E、Masson、CD31 和 COL-I 染色法进行组织学检查。实验结果表明,浓度为 10%的 PLCL/ADM 复合气凝胶具有均匀的孔径分布、良好的三维结构和与人体皮肤相当的压缩性能,能有效吸收渗出物并发挥止血作用。体内实验结果表明,该气凝胶在促进伤口愈合方面的疗效优于传统的油纱覆盖疗法和 ADM 气凝胶,可促进深部伤口快速、高质量的原位修复,从而为皮肤组织工程和临床伤口治疗提供了一种新方法。
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引用次数: 0
Aptamers in dentistry: diagnosis, therapeutics, and future perspectives. 牙科中的适配体:诊断、治疗和未来展望。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 DOI: 10.1039/d4bm01233j
Yang Yang, Zhen Yang, Hao Liu, Yongsheng Zhou

Oral health is essential to general health. The diagnosis of dental diseases and treatment planning of dental care need to be straightforward and accurate. Recent studies have reported the use of aptamers in dentistry to achieve a simple diagnosis and facilitate therapy. Aptamers comprise nucleic acid sequences that possess a strong affinity for their target. Synthesized chemically, aptamers have several advantages, including smaller size, higher stability, and lower immunogenicity compared with monoclonal antibodies. They can be used to detect biomarkers in saliva and the presence of various pathogens, or can be used as a targeted drug delivery system for disease treatment. This review highlights current research on aptamers for dental care, especially the recent progress in oral disease diagnosis and therapeutics. The challenges and unresolved problems faced by the clinical use of aptamers are also discussed. In the future, the clinical applications of aptamers will be further extended to include, for example, dental indications and regenerative dentistry.

口腔健康对全身健康至关重要。牙科疾病的诊断和牙科护理的治疗计划必须简单明了、准确无误。最近有研究报告称,在牙科中使用适配体可实现简单诊断并促进治疗。适配体由对目标具有强亲和力的核酸序列组成。与单克隆抗体相比,化学合成的适配体具有体积小、稳定性高、免疫原性低等优点。它们可用于检测唾液中的生物标记物和各种病原体的存在,也可用作治疗疾病的靶向给药系统。这篇综述重点介绍了目前用于牙科护理的适配体研究,尤其是最近在口腔疾病诊断和治疗方面取得的进展。此外,还讨论了临床使用适配体所面临的挑战和尚未解决的问题。未来,合剂的临床应用将进一步扩展到牙科适应症和再生牙科等领域。
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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 : 2024-11-11 DOI: 10.1039/d4bm01066c
Haonan Huang, Fuxin Tang, Wenchang Gan, Ruibing Li, Zehui Hou, Taicheng Zhou, 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
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 : 2024-11-11 DOI: 10.1039/d4bm00754a
Yuhong Jiang, Lijuan Jin, Wenyu Liu, Hui Liu, Xiao Liu, 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
Redox nanodrugs alleviate chronic kidney disease by reducing inflammation and regulating ROS. 氧化还原纳米药物通过减少炎症和调节 ROS 来缓解慢性肾病。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 DOI: 10.1039/d4bm00881b
Qin Wang, Xuedan Nie, Yifan Song, Haiyan Qiu, Liting Chen, He Zhu, Xueli Zhang, Mengru Yang, Xiaohui Xu, Peidan Chen, Chao Zhang, Jia Xu, Yeping Ren, Wenting Shang

Immune-mediated glomerular diseases lead to chronic kidney disease (CKD), primarily through mechanisms such as immune cell overactivation, mitochondrial dysfunction and imbalance of reactive oxygen species (ROS). We have developed an ultra-small nanodrug composed of Mn3O4 nanoparticles which is functionalized with biocompatible ligand citrate (C-Mn3O4 NPs) to maintain cellular redox balance in an animal model of oxidative injury. Furthermore, this ultra-small nanodrug, loaded with tacrolimus (Tac), regulated the activity of immune cells. We established a doxorubicin (DOX)-induced CKD model in SD rats using conditions of oxidative distress. The results demonstrate the ROS scavenging capability of Mn3O4 NPs, which mimics enzymatic activity, and the immunosuppressive effect of tacrolimus. This combination promotes targeted accumulation in the renal region with sustained drug release through the enhanced permeability and retention (EPR) effect. Tac@C-Mn3O4 protects the structural and functional integrity of mitochondria from oxidative damage while eliminating excess ROS to maintain cellular redox homeostasis, thereby suppressing the overexpression of pro-inflammatory cytokines to restore kidney function and preserve a normal kidney structure, reducing inflammation and regulating antioxidant stress pathways. This dual-pronged treatment strategy also provides novel strategies for CKD management and demonstrates substantial potential for clinical translational application.

免疫介导的肾小球疾病主要通过免疫细胞过度激活、线粒体功能障碍和活性氧(ROS)失衡等机制导致慢性肾病(CKD)。我们开发了一种由 Mn3O4 纳米粒子组成的超小型纳米药物,这种纳米药物由生物相容性配体柠檬酸盐(C-Mn3O4 NPs)功能化,可在氧化损伤动物模型中维持细胞氧化还原平衡。此外,这种负载他克莫司(Tac)的超小型纳米药物还能调节免疫细胞的活性。我们利用氧化损伤条件在 SD 大鼠体内建立了多柔比星(DOX)诱导的 CKD 模型。结果表明,Mn3O4 NPs 具有清除 ROS 的能力,可模拟酶的活性,同时还具有他克莫司的免疫抑制作用。这种组合通过增强的渗透性和滞留性(EPR)效应促进了药物在肾脏区域的靶向蓄积和持续释放。Tac@C-Mn3O4 可保护线粒体的结构和功能完整性免受氧化损伤,同时消除过量的 ROS 以维持细胞的氧化还原平衡,从而抑制促炎细胞因子的过度表达,以恢复肾功能并保持正常的肾脏结构,减少炎症并调节抗氧化应激途径。这种双管齐下的治疗策略也为慢性肾功能衰竭的治疗提供了新的策略,并显示出巨大的临床转化应用潜力。
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引用次数: 0
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