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Engineered photoresponsive biohybrids for tumor therapy. 用于肿瘤治疗的工程光反应生物杂合体
Pub Date : 2023-03-10 eCollection Date: 2023-05-01 DOI: 10.1002/SMMD.20220041
Xiaocheng Wang, Yazhi Sun, Daniel Wangpraseurt

Engineered biohybrids have recently emerged as innovative biomimetic platforms for cancer therapeutic applications. Particularly, engineered photoresponsive biohybrids hold tremendous potential against tumors due to their intriguing biomimetic properties, photoresponsive ability, and enhanced biotherapeutic functions. In this review, the design principles of engineered photoresponsive biohybrids and their latest progresses for tumor therapy are summarized. Representative engineered photoresponsive biohybrids are highlighted including biomolecules-associated, cell membrane-based, eukaryotic cell-based, bacteria-based, and algae-based photoresponsive biohybrids. Representative tumor therapeutic modalities of the engineered photoresponsive biohybrids are presented, including photothermal therapy, photodynamic therapy, synergistic therapy, and tumor therapy combined with tissue regeneration. Moreover, the challenges and future perspectives of these photoresponsive biohybrids for clinical practice are discussed.

工程生物杂交体最近成为癌症治疗应用的创新仿生平台。特别是,由于其有趣的仿生特性、光反应能力和增强的生物治疗功能,工程光反应生物杂合体具有巨大的抗肿瘤潜力。本文综述了工程光反应生物杂合体的设计原理及其在肿瘤治疗中的最新进展。具有代表性的工程光反应生物杂交种包括生物分子相关的、基于细胞膜的、基于真核细胞的、基于细菌的和基于藻类的光反应生物杂交种。介绍了具有代表性的工程光反应生物杂合体的肿瘤治疗方式,包括光热治疗、光动力治疗、协同治疗和肿瘤治疗结合组织再生。此外,还讨论了这些光反应性生物杂交体在临床实践中的挑战和未来前景。
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引用次数: 0
Organ-on-a-chip technologies for biomedical research and drug development: A focus on the vasculature. 用于生物医学研究和药物开发的芯片上器官技术:聚焦血管。
Pub Date : 2023-02-26 Epub Date: 2023-02-24 DOI: 10.1002/SMMD.20220030
Diosangeles Soto Veliz, Kai-Lan Lin, Cecilia Sahlgren

Current biomedical models fail to replicate the complexity of human biology. Consequently, almost 90% of drug candidates fail during clinical trials after decades of research and billions of investments in drug development. Despite their physiological similarities, animal models often misrepresent human responses, and instead, trigger ethical and societal debates regarding their use. The overall aim across regulatory entities worldwide is to replace, reduce, and refine the use of animal experimentation, a concept known as the Three Rs principle. In response, researchers develop experimental alternatives to improve the biological relevance of in vitro models through interdisciplinary approaches. This article highlights the emerging organ-on-a-chip technologies, also known as microphysiological systems, with a focus on models of the vasculature. The cardiovascular system transports all necessary substances, including drugs, throughout the body while in charge of thermal regulation and communication between other organ systems. In addition, we discuss the benefits, limitations, and challenges in the widespread use of new biomedical models. Coupled with patient-derived induced pluripotent stem cells, organ-on-a-chip technologies are the future of drug discovery, development, and personalized medicine.

目前的生物医学模型无法复制人类生物学的复杂性。因此,经过数十年的研究和数十亿美元的药物开发投资后,近 90% 的候选药物在临床试验中失败。尽管动物模型在生理上具有相似性,但它们往往错误地反映了人类的反应,反而引发了有关使用动物模型的伦理和社会争论。全球监管机构的总体目标是取代、减少和完善动物实验的使用,这一理念被称为 "三R原则"。为此,研究人员开发了实验替代品,通过跨学科方法提高体外模型的生物学相关性。本文重点介绍了新兴的芯片上器官技术(也称为微生理系统),重点是血管模型。心血管系统将包括药物在内的所有必要物质输送到全身,同时负责热调节和其他器官系统之间的交流。此外,我们还讨论了广泛使用新型生物医学模型的好处、局限性和挑战。器官芯片技术与源自患者的诱导多能干细胞相结合,将成为药物发现、开发和个性化医疗的未来。
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引用次数: 0
Reconstruction of the alveolar-capillary barrier in vitro based on a photo-responsive stretchable Janus membrane. 基于光响应可拉伸Janus膜的肺泡-毛细血管屏障体外重建
Pub Date : 2023-02-21 eCollection Date: 2023-02-01 DOI: 10.1002/SMMD.20220035
Changmin Shao, Ting Cao, Xiaochen Wang, Qihui Fan, Fangfu Ye

The lung is the respiratory organ of the human body, and the alveoli are the most basic functional units of the lung. Herein, a photo-responsive stretchable Janus membrane was proposed for the reconstruction of the alveolar-capillary barrier in vitro. This Janus membrane was fabricated by photocrosslinking methylacrylamide gelatin (Gelma) hydrogel and N-isoacrylamide (NIPAM) hydrogel mixed with graphene oxide (GO). The Gelma hydrogel containing large amounts of collagen provides a natural extracellular matrix environment for cell growth, while the temperature-sensitive NIPAM hydrogel combined with GO gives the membrane a light-controlled stretching property. Based on this Janus membrane, an open polydimethylsiloxane chip was established to coculture alveolar epithelial cells and vascular endothelial cells at the air-liquid interface. It was demonstrated that the alveolar epithelial cells cultured on the upper side of the Janus membrane could express epithelial cell marker protein E-cadherin and secrete alveolar surfactant. In addition, VE-cadherin, an endothelium-specific protein located at the junction between endothelial cells, was also detected in vascular endothelial cells cultured on the underside of Janus membrane. The constructed lung tissue model with the dynamically stretchable Janus membrane is well-suited for COVID-19 infection studies and drug testing.

肺是人体的呼吸器官,肺泡是肺最基本的功能单元。在此,提出了一种光响应可拉伸Janus膜,用于体外重建肺泡-毛细血管屏障。这种Janus膜是通过光交联甲基丙烯酰胺明胶(Gelma)水凝胶和N‐异丙烯酰胺(NIPAM)水凝胶与氧化石墨烯(GO)混合制备的。含有大量胶原蛋白的Gelma水凝胶为细胞生长提供了天然的细胞外基质环境,而与GO结合的温度敏感的NIPAM水凝胶使膜具有可控的拉伸性能。基于这种Janus膜,建立了一种开放的聚二甲基硅氧烷芯片,在气液界面共培养肺泡上皮细胞和血管内皮细胞。研究表明,在Janus膜上侧培养的肺泡上皮细胞可以表达上皮细胞标记蛋白E‐钙粘蛋白并分泌肺泡表面活性物质。此外,在Janus膜下侧培养的血管内皮细胞中也检测到位于内皮细胞之间连接处的内皮特异性蛋白VE‐cadherin。构建的具有动态可拉伸Janus膜的肺组织模型非常适合于COVID-19感染研究和药物测试。
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引用次数: 0
Emerging antibacterial nanozymes for wound healing. 新兴的用于伤口愈合的抗菌纳米酶
Pub Date : 2023-02-19 eCollection Date: 2023-08-01 DOI: 10.1002/SMMD.20220025
Jingyang Shan, Junyi Che, Chuanhui Song, Yuanjin Zhao

Wound infections continuously impose a huge economic and social burden on public healthcare. Despite the effective treatment of bacteria-infected wounds after using traditional antibiotics, the misuse of antibiotics usually causes the spread of bacterial resistance and decreases therapeutic outcomes. Therefore, the development of efficient antibacterial agents is urgently needed. Nanozymes, as a new generation of artificial enzymes, combine the intrinsic abilities of nanomaterials and natural enzymes. Recently, nanozymes has been widely developed to kill bacteria and treat wound infections by catalyzing the generation of various reactive oxygen species. Thus, this new concept of "antibacterial nanozymes" will promote the further advances of connecting nanozymes and bacterial elimination. To highlight these achievements, we summarize different types of antibacterial nanozymes for wound healing. It is believed that such a promising therapeutic strategy of developing antibacterial nanozymes will make a great contribution in the field of skin regeneration. We expect that antibacterial nanozymes will play the significant roles in both basic research and clinical applications.

伤口感染不断给公共医疗保健带来巨大的经济和社会负担。尽管使用传统抗生素可以有效治疗细菌感染的伤口,但抗生素的滥用通常会导致细菌耐药性的传播并降低治疗效果。因此,迫切需要开发高效的抗菌药物。纳米酶是新一代的人工酶,它结合了纳米材料和天然酶的特性。近年来,纳米酶已被广泛开发用于通过催化各种活性氧的产生来杀死细菌和治疗伤口感染。因此,“抗菌纳米酶”的新概念将促进纳米酶与细菌消除的进一步发展。为了突出这些成果,我们总结了不同类型的抗菌纳米酶用于伤口愈合。相信开发抗菌纳米酶这一有前景的治疗策略将在皮肤再生领域做出巨大贡献。我们期待抗菌纳米酶在基础研究和临床应用中发挥重要作用。
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引用次数: 0
Stimuli-responsive silk fibroin for on-demand drug delivery. 用于按需给药的刺激响应性丝素蛋白
Pub Date : 2023-02-16 eCollection Date: 2023-05-01 DOI: 10.1002/SMMD.20220019
Xiang Lin, Lijun Cai, Xinyue Cao, Yuanjin Zhao

Stimuli-responsive "smart" hydrogel biomaterials have attracted great attention in the biomedical field, especially in designing novel on-demand drug delivery systems. As a handful natural biomaterial approved by US Food and Drug Administration, silk fibroin (SF) has unique high temperature resistance as well as tunable structural composition. These properties make it one of the most ideal candidates for on-demand drug delivery. Meanwhile, recent advances in polymer modification and nanomaterials have fostered the development of various stimuli-responsive delivery systems. Here, we first review the recent advance in designing responsive SF-based delivery systems in different stimulus sources. These systems are able to release mediators in a desired manner in response to specific stimuli in active or passive manners. We then describe applications of these specially designed responsive delivery systems in wound healing, tumor therapy, as well as immunomodulation. We also discuss the future challenges and prospects of stimuli-responsive SF-based delivery systems.

刺激响应的“智能”水凝胶生物材料在生物医学领域引起了极大的关注,尤其是在设计新型按需给药系统方面。作为美国食品药品监督管理局批准的少数天然生物材料,丝素蛋白具有独特的耐高温性和可调的结构组成。这些特性使其成为按需给药的最理想候选者之一。与此同时,聚合物改性和纳米材料的最新进展促进了各种刺激响应递送系统的发展。在这里,我们首先回顾了在不同刺激源中设计基于SF的响应性递送系统的最新进展。这些系统能够以主动或被动的方式响应特定刺激,以期望的方式释放介质。然后,我们描述了这些专门设计的响应性递送系统在伤口愈合、肿瘤治疗以及免疫调节中的应用。我们还讨论了基于刺激响应SF的递送系统的未来挑战和前景。
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引用次数: 0
Emerging technologies for cardiac tissue engineering and artificial hearts. 心脏组织工程和人工心脏的新兴技术
Pub Date : 2023-02-16 eCollection Date: 2023-02-01 DOI: 10.1002/SMMD.20220040
Lingyu Sun, Yu Wang, Dongyu Xu, Yuanjin Zhao

Heart diseases, especially cardiovascular diseases, have brought heavy burden on society for their high morbidity and mortality. In clinical, heart transplantation is recognized as an effective strategy to rescue the lives of patients, while it may suffer from lack of donors and possible immune responses. In view of this, tremendous efforts have been devoted to developing alternative strategies to recover the function and promote the regeneration of cardiac tissues. As an emerging field blending cell biology and material science, tissue engineering technique allows the construction of biomimetic living complexes as organ substitutes for heart repair. In this review, we will present the recent progress in cardiac tissue engineering and artificial hearts. After introducing the critical elements in cardiac tissue engineering, we will present advanced fabrication methods to achieve scaffolds with desired micro/nanostructure design as well as the applications of these bioinspired scaffolds. We will also discuss the current dilemma and possible development direction from a biomedical perspective.

心脏病特别是心血管疾病的高发病率和高死亡率给社会带来了沉重的负担。在临床中,心脏移植被认为是挽救患者生命的有效策略,但它可能存在供体不足和可能的免疫反应。鉴于此,人们一直致力于研究恢复心脏组织功能和促进心脏组织再生的替代策略。组织工程技术是细胞生物学和材料科学相结合的新兴领域,它允许构建仿生生命复合物作为心脏修复的器官替代品。本文就心脏组织工程和人工心脏的研究进展作一综述。在介绍心脏组织工程的关键要素后,我们将介绍先进的制造方法,以实现所需的微/纳米结构设计以及这些生物启发支架的应用。我们还将从生物医学的角度讨论当前的困境和可能的发展方向。
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引用次数: 0
Encoding microcarriers for biomedicine. 用于生物医学的编码微载体
Pub Date : 2023-02-14 eCollection Date: 2023-02-01 DOI: 10.1002/SMMD.20220009
Xiaowei Wei, Yixuan Shang, Yefei Zhu, Zhuxiao Gu, Dagan Zhang

High throughput biological analysis has become an important topic in modern biomedical research and clinical diagnosis. The flow encoding scheme based on the encoding microcarriers provides a feasible strategy for the multiplexed biological analysis. Different encoding characteristics invest the microcarriers with different encoding mechanisms. Biosensor analysis, drug screening, cell culture, and the construction and evaluation of bionic organ chips can be realized by decoding the microcarriers and quantifying the detection signal intensity. In this review, the encoding strategy of microcarriers was divided into the optical and non-optical encoding approaches according to their encoding elements, and the research progress of the microcarrier encoding strategy was elaborated. Finally, we summarized the biomedical applications and predicted their future prospects.

高通量生物分析已成为现代生物医学研究和临床诊断的重要课题。基于微载体编码的流编码方案为多路生物分析提供了一种可行的策略。不同的编码特性赋予微载波不同的编码机制。通过对微载体的解码和检测信号强度的量化,可以实现生物传感器分析、药物筛选、细胞培养以及仿生器官芯片的构建和评价。本文将微载流子的编码策略根据其编码要素分为光学编码和非光学编码,并对微载流子编码策略的研究进展进行了阐述。最后,对其在生物医学领域的应用进行了总结和展望。
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引用次数: 0
Metal protoporphyrin-induced self-assembly nanoprobe enabling precise tracking and antioxidant protection of stem cells for ischemic stroke therapy. 金属原卟啉诱导的自组装纳米探针实现了对干细胞的精确跟踪和抗氧化保护,用于缺血性中风治疗
Pub Date : 2023-02-14 eCollection Date: 2023-02-01 DOI: 10.1002/SMMD.20220037
Yimeng Shu, Hui Shen, Minghua Yao, Jie Shen, Guo-Yuan Yang, Hangrong Chen, Yaohui Tang, Ming Ma

Mesenchymal stem cell (MSC)-based therapy has provided a promising strategy for the treatment of ischemic stroke, which is still restricted by the lack of long-term cell tracking strategy as well as the poor survival rate of stem cells in ischemic region. Herein, a dual-functional nanoprobe, cobalt protoporphyrin-induced nano-self-assembly (CPSP), has been developed through a cobalt protoporphyrin IX (CoPP) aggregation-induced self-assembly strategy, which combines CoPP and superparamagnetic iron oxide (SPION) via a simple solvent evaporation-driven method. Without any additional carrier materials, the obtained CPSP is featured with good biocompatibility and high proportions of active ingredients. The SPIONs in CPSPs form a cluster-like structure, endowing this nano-self-assembly with excellent T2-weighted magnetic resonance (MR) imaging performance. Furthermore, the CoPP released from CPSPs could effectively protect MSCs by upregulating heme oxygenase 1 (HO-1) expression. The in vivo cell tracing capacity of CPSPs is confirmed by monitoring the migration of labeled MSCs with MR imaging in a middle cerebral artery occlusion mouse model. More importantly, the sustained release of CoPP from CPSPs improves the survival of transplanted MSCs and promotes neural repair and neurobehavioral recovery of ischemic mice. Overall, this work presents a novel dual-functional nanoagent with an ingenious design for advancing MSC-based therapy.

基于间充质干细胞(MSC)的治疗为缺血性卒中的治疗提供了一种很有前途的策略,但由于缺乏长期的细胞追踪策略以及干细胞在缺血性区域的存活率低,该策略仍受到限制。本文通过钴原卟啉IX(CoPP)聚集诱导的自组装策略开发了一种双功能纳米探针,即钴原卟啉诱导的纳米自组装(CPSP),该策略通过简单的溶剂蒸发驱动方法将CoPP和超顺磁性氧化铁(SPION)相结合。在不添加任何载体材料的情况下,所获得的CPSP具有良好的生物相容性和高比例的活性成分。CPSP中的SPION形成簇状结构,赋予这种纳米自组装优异的T2加权磁共振(MR)成像性能。此外,从CPSP释放的CoPP可以通过上调血红素加氧酶1(HO‐1)的表达来有效保护MSC。通过在大脑中动脉闭塞小鼠模型中用MR成像监测标记的MSCs的迁移,证实了CPSPs的体内细胞追踪能力。更重要的是,CPSP持续释放CoPP提高了移植MSCs的存活率,并促进了缺血小鼠的神经修复和神经行为恢复。总的来说,这项工作提出了一种新颖的双功能纳米制剂,其巧妙的设计用于推进基于MSC的治疗。
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引用次数: 0
Nurturing the marriages of urinary liquid biopsies and nano-diagnostics for precision urinalysis of prostate cancer. 促进尿液活检和纳米诊断的结合,用于前列腺癌的精确尿液分析
Pub Date : 2023-02-14 eCollection Date: 2023-02-01 DOI: 10.1002/SMMD.20220020
Caizhi Liao, Zhihao Wu, Chan Lin, Xiaofeng Chen, Yaqun Zou, Wan Zhao, Xin Li, Guangqi Huang, Baisheng Xu, Giovanni E Briganti, Yan Qi, Xianshu Wang, Tao Zeng, Alain Wuethrich, Hongzhi Zou

Prostate cancer remains the second-most common cancer diagnosed in men, despite the increasingly widespread use of serum prostate-specific antigen (PSA) screening. The controversial clinical implications and cost benefits of PSA screening have been highlighted due to its poor specificity, resulting in a high rate of overdiagnosis and underdiagnosis. Thus, the development of novel biomarkers for prostate cancer detection remains an intriguing challenge. Urine is emerging as a source for prostate cancer biomarker discovery. Currently, new urine biomarkers already outperform serum PSA in clinical diagnosis. Meanwhile, the advances in nanotechnology have provided a suite of diagnostic tools to study prostate cancer in more detail, sparking a new era of biomarker discoveries. In this review, we envision that future prostate cancer diagnosis will probably integrate multiplex nano-diagnostic approaches to detect novel urinary biomarkers. However, challenges remain in differentiating indolent from aggressive cancers to better inform treatment decisions, and clinical translation still needs to be overcome.

尽管血清前列腺特异性抗原(PSA)筛查的应用越来越广泛,但前列腺癌仍然是男性诊断的第二大常见癌症。由于PSA筛查的特异性较差,导致高过诊断率和低诊断率,因此其临床意义和成本效益备受争议。因此,开发用于前列腺癌检测的新型生物标志物仍然是一个有趣的挑战。尿液正在成为发现前列腺癌生物标志物的来源。目前,新的尿液生物标志物在临床诊断中已经优于血清PSA。与此同时,纳米技术的进步提供了一套诊断工具,可以更详细地研究前列腺癌,从而开启了生物标志物发现的新时代。在这篇综述中,我们设想未来的前列腺癌诊断可能会整合多种纳米诊断方法来检测新的尿液生物标志物。然而,在区分惰性和侵袭性癌症以更好地为治疗决策提供信息方面仍然存在挑战,临床转化仍然需要克服。
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引用次数: 0
Microfluidic preparation of optical sensors for biomedical applications. 用于生物医学应用的光学传感器的微流体制备
Pub Date : 2023-02-12 eCollection Date: 2023-02-01 DOI: 10.1002/SMMD.20220027
Qiao Wang, Chong Wang, Xinyuan Yang, Jiali Wang, Zhuohao Zhang, Luoran Shang

Optical biosensors are platforms that translate biological information into detectable optical signals, and have extensive applications in various fields due to their characteristics of high sensitivity, high specificity, dynamic sensing, etc. The development of optical sensing materials is an important part of optical sensors. In this review, we emphasize the role of microfluidic technology in the preparation of optical sensing materials and the application of the derived optical sensors in the biomedical field. We first present some common optical sensing mechanisms and the functional responsive materials involved. Then, we describe the preparation of these sensing materials by microfluidics. Afterward, we enumerate the biomedical applications of these optical materials as biosensors in disease diagnosis, drug evaluation, and organ-on-a-chip. Finally, we discuss the challenges and prospects in this field.

光学生物传感器是将生物信息转化为可检测的光信号的平台,具有高灵敏度、高特异度、动态传感等特点,在各个领域有着广泛的应用。光传感材料的发展是光传感器的重要组成部分。本文综述了微流控技术在光学传感材料制备中的作用及其衍生光学传感器在生物医学领域的应用。我们首先介绍了一些常见的光学传感机制和所涉及的功能响应材料。然后介绍了微流体传感材料的制备方法。随后,我们列举了这些光学材料作为生物传感器在疾病诊断、药物评估和器官芯片上的生物医学应用。最后,讨论了该领域面临的挑战和前景。
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引用次数: 0
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Smart medicine
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