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Construction of an uricase/catalase/curcumin-co-loaded drug delivery system and its effect on hyper-uric acid-induced kidney injury 尿酸盐/催化剂/姜黄素载药系统的构建及其对高尿酸诱导的肾损伤的影响
Q1 Engineering Pub Date : 2024-06-06 DOI: 10.1016/j.smaim.2024.05.002
Yang Zhang , Xiaobo Li , Chunling Liang , Jianjia Feng , Chuyi Yu , Weichi Jiang , Keneng Cai , Wanying Chen , Wenli Cai , Feng Zeng , Qin Xu , Peng Chen , Jianming Liang

Hyper-uric acid (UA)-induced kidney injury (HAKI) is caused by the deposition of excess blood UA into the kidneys. We confined molecules of uricase (URI), catalase (CAT), and curcumin (Cur) to a single structure (UC/Cur) while retaining their enzymatic activities via a cross-linking complexation reaction between tannic acid and FeCl3 for treating HAKI. Simultaneously, bovine serum albumin (BSA)-UC/Cur nanoparticles were successfully prepared by interlinking the disulfide bonds of BSA with the enzyme complex via Tris(2-carboxyethyl) phosphine(TCEP) to form sulfhydryl groups. BSA-UC/Cur significantly attenuated MSU-induced NLRP3 inflammasome pathway activation and apoptosis in NRK-52e cells by eliminating UA crystals and intracellular reactive oxygen species. More importantly, treatment with BSA-UC/Cur stabilized blood UA concentrations and lowered proximal tubular protein levels, mitochondrial swelling, and fibrotic areas, renducing the expression of matrix metalloproteinase (MMP)2, MMP9, and NLRP3 while, increasing the expression of tight-junction proteins ZO1 and occludin as well as that of TIMP-1, in HAKI model rats. In addition, BSA-UC/Cur nanoparticles reduced the subpopulation ratios of CD8+ T cells and M1 macrophages and increased those of M2 macrophages and Treg cells. Preliminary in-vivo trials showed that long-term intravenous treatment with BSA-UC/Cur is safe. Therefore, BSA-UC/Cur could be a potential nanotherapeutic agent for HAKI.

高尿酸(UA)诱导的肾损伤(HAKI)是由血液中过量的尿酸沉积到肾脏引起的。我们通过鞣酸与氯化铁的交联复合物反应,将尿酸酶(URI)、过氧化氢酶(CAT)和姜黄素(Cur)分子限制在单一结构(UC/Cur)中,同时保留其酶活性,用于治疗 HAKI。同时,通过三(2-羧乙基)膦(TCEP)将牛血清白蛋白(BSA)的二硫键与酶复合物交联形成巯基,成功制备了牛血清白蛋白-UC/Cur纳米颗粒。BSA-UC/Cur通过消除UA晶体和细胞内活性氧,明显减轻了MSU诱导的NLRP3炎性体通路激活和NRK-52e细胞的凋亡。更重要的是,BSA-UC/Cur 能稳定 HAKI 模型大鼠血液中 UA 的浓度,降低近端肾小管蛋白水平、线粒体肿胀和纤维化面积,减少基质金属蛋白酶(MMP)2、MMP9 和 NLRP3 的表达,同时增加紧密连接蛋白 ZO1 和 occludin 以及 TIMP-1 的表达。此外,BSA-UC/Cur 纳米粒子还降低了 CD8+ T 细胞和 M1 巨噬细胞的亚群比率,增加了 M2 巨噬细胞和 Treg 细胞的亚群比率。初步体内试验表明,长期静脉注射 BSA-UC/Cur 是安全的。因此,BSA-UC/Cur 可能是一种潜在的 HAKI 纳米治疗剂。
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引用次数: 0
Smart materials in medicine 5th anniversary 智能材料在医学中的应用 5 周年
Q1 Engineering Pub Date : 2024-05-14 DOI: 10.1016/j.smaim.2024.05.001
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引用次数: 0
Inhalable nanomedicine for lung cancer treatment 用于治疗肺癌的可吸入纳米药物
Q1 Engineering Pub Date : 2024-04-10 DOI: 10.1016/j.smaim.2024.04.001
Shuiying Zhang , Rui Li , Tong Jiang , Yihan Gao , Kai Zhong , Hong Cheng , Xin Chen , Shiying Li

Lung cancer has surpassed other types of cancer to become the primary cause of cancer-related deaths. Surgery stands as the foremost clinical treatment strategy available for tackling this condition, but it receives a low efficiency for most patients. In recent years, some adjuvant therapies are employed to improve the lung cancer treatment efficiency, such as chemotherapy, targeted therapy and immunotherapy. However, these strategies have not significantly increased overall survival of patients. Additionally, the random distribution of drugs will induce severe side effects. Nanomedicines have got great attentions to boost drug effect and reduce adverse reactions, including liposome-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and exosomes. Importantly, nanomedicines contribute to improving drug bioavailability, stability and residency in target regions. Benefiting from the physiological characteristics of lung, the inhaled pulmonary delivery strategy in combination with nanomedicine will provide a non-invasive and effective strategy for treating lung cancer. Furthermore, the use of targeting ligands enables precise delivery of loaded drugs to lung cancer cells. Inhaled nanomedicine exhibits unique distribution and sustained release behaviors in the alveoli, amplifying the therapeutic effect and reducing side effects. This review aims to discuss various inhaled methods of delivering nanomedicine to treat lung cancer and also summarizes the clearance mechanism of nanomedicine in the lung. Overall, this review focuses on the application of different inhalable nanomedicines, which may inspire the development of more effective treatments against lung cancer.

肺癌已超过其他类型的癌症,成为癌症相关死亡的主要原因。手术是目前临床上治疗肺癌的最主要手段,但对大多数患者来说,手术治疗效率较低。近年来,为了提高肺癌的治疗效率,一些辅助疗法被采用,如化疗、靶向治疗和免疫治疗。然而,这些策略并没有明显提高患者的总生存率。此外,药物的随机分布会引起严重的副作用。为提高药物疗效、减少不良反应,纳米药物受到了广泛关注,包括脂质体纳米颗粒、聚合物纳米颗粒、无机纳米颗粒和外泌体。重要的是,纳米药物有助于提高药物的生物利用度、稳定性和在目标区域的驻留率。利用肺部的生理特性,吸入肺部给药策略与纳米药物相结合,将为治疗肺癌提供一种非侵入性的有效策略。此外,靶向配体的使用可将负载的药物精确输送到肺癌细胞。吸入式纳米药物在肺泡中表现出独特的分布和持续释放行为,可扩大治疗效果并减少副作用。本综述旨在讨论各种吸入式纳米药物治疗肺癌的方法,并总结纳米药物在肺部的清除机制。总体而言,这篇综述侧重于不同可吸入纳米药物的应用,这可能会启发开发更有效的肺癌治疗方法。
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引用次数: 0
Hydrogel-fiber-mesh-based 3D cell cultures: A new method for studying pituitary tumors 基于水凝胶-纤维网的三维细胞培养:研究垂体瘤的新方法
Q1 Engineering Pub Date : 2024-03-27 DOI: 10.1016/j.smaim.2024.03.004
Wooju Jeong , Sungrok Wang , Yumin Kim , Soohyun Lee , Minhu Huang , Jaeil Park , Myung-Han Yoon , Chang-Myung Oh , Cheol Ryong Ku

Acromegaly is a challenging medical condition that arises from the excessive production of growth hormones and the insulin-like growth factor 1 in the pituitary gland. While surgery is the primary treatment for acromegaly, medication is increasingly being used in patients who are unsuitable for surgery or have experienced treatment failure. Despite advancements in medical and surgical therapies, the treatment of acromegaly remains challenging. In this research, a three-dimensional (3D) in-vitro cell culture model for pituitary adenoma research was developed using hydrogel fiber meshes (HFMs) and GH3 cells. Electrospun nanofibers based on polyvinyl alcohol and polyacrylic acid were converted into HFMs by hydrogelification with the leaching of electrosprayed cellulose acetate beads for porosity enhancement. GH3 cells grown in the 3D model exhibited increased dispersion and upregulation of the somatostatin receptor subtypes 2 and 5 compared to those grown in traditional 2D cultures, as well as high sensitivity to somatostatin analogs and tumor-like profiles (as indicated by functional assays and transcriptome analysis, respectively). Therefore, the proposed 3D model accurately represents the physiological response to pituitary-adenoma therapeutic agents. This study highlights the potential of HFMs as a versatile platform for 3D in-vitro cell culture models that can be employed for pituitary adenoma research. Moreover, the proposed 3D cell culture model may contribute to a deeper understanding of tumor biology and facilitate the development of effective therapeutic strategies for acromegaly.

肢端肥大症是一种具有挑战性的病症,是由于垂体过量分泌生长激素和胰岛素样生长因子 1 引起的。虽然手术是治疗肢端肥大症的主要方法,但药物治疗也越来越多地用于不适合手术或治疗失败的患者。尽管药物和手术疗法取得了进步,但肢端肥大症的治疗仍然充满挑战。本研究利用水凝胶纤维网(HFMs)和GH3细胞开发了一种用于垂体腺瘤研究的三维(3D)体外细胞培养模型。以聚乙烯醇和聚丙烯酸为基础的电纺纳米纤维通过水凝胶化转化为水凝胶纤维网,并浸出电喷醋酸纤维素微珠以提高孔隙率。与传统的二维培养相比,在三维模型中生长的 GH3 细胞表现出更高的分散性和上调体生长抑素受体亚型 2 和 5,以及对体生长抑素类似物的高敏感性和肿瘤样特征(分别由功能测定和转录组分析表明)。因此,所提出的三维模型准确地反映了垂体腺瘤治疗药物的生理反应。这项研究凸显了高频膜作为三维体外细胞培养模型多功能平台的潜力,可用于垂体腺瘤研究。此外,所提出的三维细胞培养模型可能有助于加深对肿瘤生物学的理解,促进开发有效的肢端肥大症治疗策略。
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引用次数: 0
Mechano-immunological checkpoints: An emerging strategy for investigation and evaluation of disease and therapeutics 机械免疫检查点:调查和评估疾病与疗法的新兴战略
Q1 Engineering Pub Date : 2024-03-26 DOI: 10.1016/j.smaim.2024.03.002
Wenhui Hu , Cuifang Wu , Jinhua Long , Zhu Zeng

Over the past decades, increasing evidence has indicated that multiple mechanical signals with different magnitude and pattern, including fluid flow-derived shear stress, topology of extracellular matrix (ECM), substrate stiffness, tension or compression, are now emerging as important orchestrators of immune response under physiological and pathophysiological conditions. Correspondingly, the extrinsic mechanical signals may confer the unique mechanophenotypes on cells, which coupled with their immunophenotypes, determines the ultimate type of immune response. Therefore, the concept of mechano-immunological checkpoints is proposed, which concerns the featured mechanical signals and the typical mechanophenotypes of immune cells, making it possible to elucidate and treat immune-associated disease from the mechanical viewpoint.

过去几十年来,越来越多的证据表明,在生理和病理生理条件下,多种不同强度和模式的机械信号,包括流体流动产生的剪切应力、细胞外基质(ECM)的拓扑结构、基质的硬度、张力或压缩力,正在成为免疫反应的重要协调者。相应地,外在机械信号可能会赋予细胞独特的机械表型,再加上细胞的免疫表型,决定了最终的免疫反应类型。因此,我们提出了 "机械免疫检查点"(mechano-immunological checkpoints)的概念,它涉及免疫细胞的特征机械信号和典型机械表型,使从机械角度阐明和治疗免疫相关疾病成为可能。
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引用次数: 0
Nanoparticles (NPs)-mediated targeted regulation of redox homeostasis for effective cancer therapy 纳米粒子(NPs)介导的氧化还原平衡靶向调节用于有效治疗癌症
Q1 Engineering Pub Date : 2024-03-23 DOI: 10.1016/j.smaim.2024.03.003
Zixuan Zhao , Yuan Cao , Rui Xu , Junyue Fang , Yuxuan Zhang , Xiaoding Xu , Linzhuo Huang , Rong Li

Although characterized by high reactive oxygen species (ROS) generation, cancer cells maintain redox homeostasis to avoid severe damage (e.g., DNA, protein, and plasma membrane dysfunction) and facilitate cancer progression. Emerging evidence has indicated that targeting the regulation of redox homeostasis to amplify oxidative stress is of value in cancer therapy. However, therapeutic agents like nucleic acids, small molecular inhibitors, and chemotherapeutic drugs fail to exert effective cancer inhibition due to their low bioavailability, susceptibility to serum enzymes, and inefficiency in cell membrane penetrating. Therefore, specific delivery vectors are required to facilitate the intracellular delivery of anti-tumor drugs. In the past few decades, various engineered nanomaterials have been designed and developed for drug delivery. In particular, rational nanoparticles (NPs) have garnered more attention due to their splendid long circulation ability, modification capacity, and stimulation-responded release. In this review, the methods of ROS generation and ROS-regulated signaling in cancer development were firstly briefly introduced. The anti-oxidant system, including the metabolism shifting and anti-oxidant genes, were next reviewed, and the strategies of NPs-mediated targeted regulation of redox homeostasis were emphatically discussed. The main strategies include NPs-induced delivery of nucleic acids, small molecule inhibitors, chemotherapeutic agents, radiosensitizers, and NPs-induced ROS generation and GSH depletion. The future development of NP-mediated redox dyshomeostasis in cancer therapy and their challenges in clinical translation were finally discussed.

虽然癌细胞的特点是产生大量活性氧(ROS),但它们会维持氧化还原平衡,以避免严重损伤(如 DNA、蛋白质和质膜功能障碍),并促进癌症进展。新的证据表明,以调节氧化还原平衡为目标放大氧化应激在癌症治疗中具有价值。然而,核酸、小分子抑制剂和化疗药物等治疗剂由于生物利用度低、易受血清酶的影响以及细胞膜穿透效率低等原因,无法发挥有效的癌症抑制作用。因此,需要特定的递送载体来促进抗肿瘤药物的细胞内递送。在过去几十年中,人们设计和开发了各种用于给药的工程纳米材料。其中,合理纳米颗粒(NPs)因其出色的长循环能力、修饰能力和刺激响应释放能力而受到更多关注。在这篇综述中,首先简要介绍了癌症发展过程中 ROS 的产生方法和 ROS 调节的信号传导。接着,综述了抗氧化系统,包括代谢转换和抗氧化基因,并重点讨论了 NPs 介导的靶向调节氧化还原平衡的策略。主要策略包括 NPs 诱导的核酸、小分子抑制剂、化疗药物、放射增敏剂的递送,以及 NPs 诱导的 ROS 生成和 GSH 消耗。最后讨论了 NP 介导的氧化还原失衡在癌症治疗中的未来发展及其在临床转化中面临的挑战。
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引用次数: 0
Artificial intelligence (AI) meets biomaterials and biomedicine 人工智能(AI)与生物材料和生物医学的结合
Q1 Engineering Pub Date : 2024-03-15 DOI: 10.1016/j.smaim.2024.03.001
Shuyan Han , Jun Wu

With the rapid progress of information technology and life sciences, artificial intelligence (AI) technology has substantially changed the way in many areas of biomaterials and biomedicine, including biomaterials and formulation design, drug development, preclinical study, clinical diagnosis and treatment, as well as health management. This perspective outlines the key issues of AI in the fields of biomaterials and biomedicine applications, and analyzes some opportunities and challenges of AI in the biomedical and clinical development. The gap between experts from multiple disciplines and fields needs to be narrowed, and common participation should be applied to open the next frontier of integrated AI-biomedicine.

随着信息技术和生命科学的飞速发展,人工智能(AI)技术在生物材料和生物医药的许多领域,包括生物材料和制剂设计、药物开发、临床前研究、临床诊断和治疗以及健康管理等方面都发生了实质性的改变。本视角概述了人工智能在生物材料和生物医学应用领域的关键问题,并分析了人工智能在生物医学和临床开发中的一些机遇和挑战。需要缩小多学科、多领域专家之间的差距,共同参与,开辟人工智能-生物医学融合的下一个前沿领域。
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引用次数: 0
Heparin-loaded hierarchical fiber/microsphere scaffolds for anti-inflammatory and promoting wound healing 用于消炎和促进伤口愈合的肝素负载分层纤维/微球支架
Q1 Engineering Pub Date : 2024-02-27 DOI: 10.1016/j.smaim.2024.02.002
Kai Cheng , Yan Deng , Lin Qiu , Shuhang Song , Lei Chen , LinGe Wang , Qianqian Yu

Chronic non-healing wounds induced by oxidative stress and inflammation can activate inflammatory cells and produce large amounts of inflammatory mediators, which fail to maintain homeostasis in the skin and delay the wound-healing process. To tackle this issue, heparin-loaded hierarchical composite scaffolds comprised of electrospun fibers and electrosprayed microspheres were prepared to act as an effective anti-inflammatory wound dressing. Microspheres with different electrosprayed densities were deposited into the surface of the electrospun fibers for the improvement of surface topographical cues and cellular activities. The results indicated that the electrospun fibers followed by electrosprayed for 3 ​min to fabricate the composite fiber/microsphere scaffolds contributed to the best performance in terms of promoting cellular activities, with no obvious cytotoxicity, good adhesion morphology, and the fastest cell migration rate. In addition, a suitable amount of heparin was added to the composite scaffolds to alleviate inflammation. The significant adsorption efficiency of heparin-loaded composite scaffolds on inflammatory mediator MCP-1 indicates a favorable anti-inflammation effect in vitro. Furthermore, the heparin-loaded hierarchical scaffolds accelerated the pace of inflammatory wound healing in vivo when compared to commercial 3 ​M Tegaderm and non-heparin-loaded scaffolds. Our work provided a facile strategy for fabricating heparin-loaded hierarchical fiber/microsphere scaffolds to modulate cellular activities via topographical cues and accelerating the inflammatory wound healing process by electrostatic interactions between heparin and MCP-1. These findings suggested that the heparin-loaded hierarchical scaffold was expected to be a promising dressing for inflammatory wound healing.

氧化应激和炎症诱发的慢性不愈合伤口会激活炎症细胞并产生大量炎症介质,从而无法维持皮肤的平衡,延缓伤口愈合过程。针对这一问题,研究人员制备了由电纺纤维和电喷微球组成的肝素负载分层复合支架,以作为一种有效的抗炎伤口敷料。不同电喷密度的微球沉积在电纺纤维表面,以改善表面地形线索和细胞活性。结果表明,电纺纤维经 3 分钟电喷后制成的纤维/微球复合支架在促进细胞活性方面性能最佳,无明显细胞毒性,粘附形态良好,细胞迁移率最快。此外,复合支架中还添加了适量的肝素,以减轻炎症反应。肝素负载复合支架对炎症介质 MCP-1 有明显的吸附效率,表明其在体外具有良好的抗炎效果。此外,与商用 3 M Tegaderm 和非肝素负载支架相比,肝素负载分层支架加快了体内炎症伤口愈合的速度。我们的研究为制造肝素负载分层纤维/微球支架提供了一种简便的策略,通过地形线索调节细胞活性,并通过肝素和 MCP-1 之间的静电相互作用加速炎症伤口愈合过程。这些研究结果表明,肝素负载的分层支架有望成为一种用于炎症伤口愈合的敷料。
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引用次数: 0
Machine learning for polyphenol-based materials 多酚基材料的机器学习
Q1 Engineering Pub Date : 2024-02-10 DOI: 10.1016/j.smaim.2024.02.001
Shengxi Jiang , Peiji Yang , Yujia Zheng , Xiong Lu , Chaoming Xie

Polyphenol-based materials, primarily composed of polyphenolic compounds, have attracted considerable attention due to their unique chemical structures and biological activities. However, there are many derivatives of polyphenols, resulting in the complexity and diversity of polyphenol-based materials. Traditional methods are difficult to meet the rapid development of polyphenol-based materials. Machine learning, known for its proficiency in predicting performance, optimizing synthesis processes, and designing novel materials, offers significant potential in the intelligent design and applications of polyphenol-based materials. In this review, we summarize the recent advancements in the research and development of polyphenol-based materials and machine learning. The intersection of polyphenol-based materials and machine learning is also discussed, including their applications in biomedical, environmental, and energy fields. The challenges and prospects for the future development of polyphenol-based materials based on machine learning are highlighted.

以多酚化合物为主要成分的多酚基材料因其独特的化学结构和生物活性而备受关注。然而,多酚的衍生物众多,导致多酚基材料的复杂性和多样性。传统方法难以满足多酚基材料的快速发展。机器学习以其在预测性能、优化合成工艺和设计新型材料方面的能力而著称,为多酚基材料的智能设计和应用提供了巨大的潜力。在本综述中,我们将总结多酚基材料和机器学习的最新研发进展。此外,还讨论了多酚基材料与机器学习的交集,包括它们在生物医学、环境和能源领域的应用。重点介绍了基于机器学习的多酚基材料未来发展所面临的挑战和前景。
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引用次数: 0
Recent progress of 3D printed vascularized tissues and organs 三维打印血管化组织和器官的最新进展
Q1 Engineering Pub Date : 2024-01-12 DOI: 10.1016/j.smaim.2024.01.001
Ke Zheng , Muyuan Chai , Bingping Luo , Kezhao Cheng , Zhenxing Wang , Nan Li , Xuetao Shi

Since the need for vascular networks to supply oxygen and nutrients while expelling metabolic waste, most cells can only survive within 200 ​μm of blood vessels; thus, the construction of well-developed blood vessel networks is essential for the manufacture of artificial tissues and organs. Three-dimensional (denoted as 3D) printing is a scalable, reproducible and high-precision manufacturing technology. In the past several years, there have been many breakthroughs in building various vascularized tissues, greatly promoting the development of biological tissue engineering. This paper highlights the latest progress of 3D printed vascularized tissues and organs, including the heart, liver, lung, kidney, and penis. We also discuss the application status and potential of the above printed tissues, and prospect the further requirement of 3D printing technology for manufacturing clinically useable vascularized tissues.

由于需要血管网络提供氧气和养分,同时排出代谢废物,大多数细胞只能在距离血管 200 μm 的范围内生存;因此,构建发达的血管网络对于制造人工组织和器官至关重要。三维(3D)打印是一种可扩展、可复制和高精度的制造技术。在过去几年中,各种血管组织的构建取得了许多突破性进展,极大地推动了生物组织工程学的发展。本文重点介绍了三维打印血管化组织和器官的最新进展,包括心脏、肝脏、肺脏、肾脏和阴茎。我们还讨论了上述打印组织的应用现状和潜力,并展望了制造临床可用血管化组织对 3D 打印技术的进一步要求。
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引用次数: 0
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Smart Materials in Medicine
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