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Hydrogel and nanoparticle carriers for kidney disease therapy: trends and recent advancements 水凝胶和纳米颗粒载体用于肾脏疾病治疗:趋势和最新进展
Pub Date : 2022-05-09 DOI: 10.1088/2516-1091/ac6e18
Xurui Gu, Zhen Liu, Yi-fan Tai, Ling-yun Zhou, Kun Liu, D. Kong, Adam C. Midgley, Xiao-cong Zuo
Achieving local therapeutic agent concentration in the kidneys through traditional systemic administration routes have associated concerns with off-target drug effects and toxicity. Additionally, kidney diseases are often accompanied by co-morbidities in other major organs, which negatively impacts drug metabolism and clearance. To circumvent these issues, kidney-specific targeting of therapeutics aims to achieve the delivery of controlled doses of therapeutic agents, such as drugs, nucleic acids, peptides, or proteins, to kidney tissues in a safe and efficient manner. Current carrier material approaches implement macromolecular and polyplex hydrogel constructs, prodrug strategies, and nanoparticle (NP)-based delivery technologies. In the context of multidisciplinary and cross-discipline innovations, the medical and bioengineering research fields have facilitated the rapid development of kidney-targeted therapies and carrier materials. In this review, we summarize the current trends and recent advancements made in the development of carrier materials for kidney disease targeted therapies, specifically hydrogel and NP-based strategies for acute kidney disease, chronic kidney disease, and renal cell carcinoma. Additionally, we discuss the current limitations in carrier materials and their delivery mechanisms.
通过传统的全身给药途径在肾脏中实现局部治疗剂浓度与脱靶药物作用和毒性有关。此外,肾脏疾病通常伴有其他主要器官的合并症,这会对药物代谢和清除产生负面影响。为了避免这些问题,肾脏特异性靶向治疗旨在实现以安全有效的方式向肾脏组织递送控制剂量的治疗剂,如药物、核酸、肽或蛋白质。目前的载体材料方法实现了大分子和多肽水凝胶构建、前药策略和基于纳米颗粒(NP)的递送技术。在多学科和跨学科创新的背景下,医学和生物工程研究领域促进了肾脏靶向治疗和载体材料的快速发展。在这篇综述中,我们总结了肾脏疾病靶向治疗载体材料的发展趋势和最新进展,特别是用于急性肾脏疾病、慢性肾脏疾病和肾细胞癌的水凝胶和NP策略。此外,我们还讨论了目前载体材料及其输送机制的局限性。
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引用次数: 4
Physiological closed-loop control in critical care: opportunities for innovations 重症监护中的生理闭环控制:创新的机会
Pub Date : 2022-05-05 DOI: 10.1088/2516-1091/ac6d36
J. Hahn, O. Inan
Physiological closed-loop control (PCLC) systems are a key enabler for automation and clinician support in medicine, including, but not limited to, patient monitoring, diagnosis, clinical decision making, and therapy delivery. Existing body of work has demonstrated that PCLC systems hold the promise to advance critical care as well as a wide range of other domains in medicine bearing profound implications in quality of life, quality of care, and human wellbeing. However, the state-of-the-art PCLC technology in critical care is associated with long-standing limitations related to its development and assessment, including (a) isolated and loop-by-loop PCLC design without sufficient account for multi-faceted patient physiology, (b) suboptimal choice of therapeutic endpoints, (c) concerns related to collective safety originating from multi-PCLC interferences, and (d) premature PCLC assessment methodology. Such limitations naturally motivate research to generate new knowledge and create innovative methods. In this perspective, we propose several high-reward opportunities that can accelerate the advances in PCLC systems, which may be explored by deep fusion and collaboration among multiple disciplines including physiological systems and signals analysis, control and estimation, machine learning and artificial intelligence, and wearable sensing and embedded computing technologies.
生理闭环控制(PCLC)系统是医学自动化和临床医生支持的关键推动者,包括但不限于患者监测、诊断、临床决策和治疗提供。现有的工作表明,PCLC系统有望推进重症监护以及医学中的广泛其他领域,对生活质量、护理质量和人类福祉产生深远影响。然而,重症监护中最先进的PCLC技术与其开发和评估相关的长期局限性有关,包括(a)在没有充分考虑多方面患者生理学的情况下进行隔离和逐环PCLC设计,(b)治疗终点的次优选择,(c)多PCLC干扰引起的集体安全问题,以及(d)PCLC评估方法不成熟。这种局限性自然促使研究产生新的知识并创造创新的方法。从这个角度来看,我们提出了几个可以加速PCLC系统进步的高回报机会,可以通过生理系统和信号分析、控制和估计、机器学习和人工智能、可穿戴传感和嵌入式计算技术等多个学科之间的深度融合和协作来探索。
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引用次数: 6
Recent progress in the use of thermogelling polymers for treatment of ophthalmic conditions 热凝胶聚合物用于眼科疾病治疗的最新进展
Pub Date : 2022-04-11 DOI: 10.1088/2516-1091/ac6641
Jasmin Omar, C. A. Dreiss, X. Loh
Ocular diseases have serious implications on patients’ lives, with the majority causing blindness if left untreated. In 2020 it was estimated that 43 million people were blind worldwide which is expected to increase to 61 million by 2050. Due to the eye’s complex structure and defence mechanisms, there has been an ongoing challenge to deliver drugs which can penetrate the eyes’ barrier and reside at the site of action. Recent advances focus on the use of hydrogels, in particular temperature-responsive hydrogels, ‘thermogels’, to improve the properties of current therapies. Formulating a hydrogel-based system has shown to increase the bioavailability and biodegradability, provide a sustained release profile, enhance the drug permeation and residence time, as well as reduce the frequency of applications. This article provides a review of progress made over the past 5 years (2017–2021) using ‘thermogels’ for the treatment of some common or life-threatening ophthalmic conditions.
眼病对患者的生命有严重影响,如果不及时治疗,大多数眼病会导致失明。据估计,2020年全世界有4300万人失明,预计到2050年将增加到6100万人。由于眼睛的复杂结构和防御机制,如何递送能够穿透眼睛屏障并停留在作用部位的药物一直是一个挑战。最近的进展集中在水凝胶的使用上,特别是温度响应水凝胶,“热凝胶”,以改善当前疗法的性能。制备水凝胶体系已被证明可以提高生物利用度和生物降解性,提供缓释特性,增强药物渗透和停留时间,并减少应用频率。本文回顾了过去5年(2017-2021)使用“热凝胶”治疗一些常见或危及生命的眼科疾病的进展。
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引用次数: 0
3D Coaxial Bioprinting: Process Mechanisms, Bioinks and Applications. 三维同轴生物打印:工艺机制、生物墨水和应用。
IF 5 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-04-01 Epub Date: 2022-04-20 DOI: 10.1088/2516-1091/ac631c
Tarun Shyam Mohan, Pallab Datta, Sepehr Nesaei, Veli Ozbolat, Ibrahim T Ozbolat

In the last decade, bioprinting has emerged as a facile technique for fabricating tissues constructs mimicking the architectural complexity and compositional heterogeneity of native tissues. Amongst different bioprinting modalities, extrusion-based bioprinting (EBB) is the most widely used technique. Coaxial bioprinting, a type of EBB, enables fabrication of concentric cell-material layers and enlarges the scope of EBB to mimic several key aspects of native tissues. Over the period of development of bioprinting, tissue constructs integrated with vascular networks, have been one of the major achievements made possible largely by coaxial bioprinting. In this review, current advancements in biofabrication of constructs with coaxial bioprinting are discussed with a focus on different bioinks that are particularly suitable for this modality. This review also expounds the properties of different bioinks suitable for coaxial bioprinting and then analyses the key achievements made by the application of coaxial bioprinting in tissue engineering, drug delivery and in-vitro disease modelling. The major limitations and future perspectives on the critical factors that will determine the ultimate clinical translation of the versatile technique are also presented to the reader.

在过去的十年中,生物打印技术已成为模仿原生组织的结构复杂性和成分异质性制造组织构建体的一种简便技术。在各种生物打印模式中,挤压式生物打印(EBB)是应用最广泛的技术。同轴生物打印是 EBB 的一种,可制造同心的细胞-材料层,并扩大了 EBB 的范围,使其能够模仿原生组织的几个关键方面。在生物打印技术的发展过程中,与血管网络相结合的组织构建物是主要通过同轴生物打印技术实现的重大成就之一。在这篇综述中,我们讨论了目前利用同轴生物打印技术进行生物制造的进展,重点是特别适用于这种模式的不同生物墨水。本综述还阐述了适合同轴生物打印的不同生物墨水的特性,然后分析了在组织工程、药物输送和体外疾病建模中应用同轴生物打印所取得的主要成就。此外,还向读者介绍了决定这一多功能技术最终临床应用的关键因素的主要局限性和未来展望。
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引用次数: 0
Recent progress in bioactive gas delivery for cancer immunotherapy 癌症免疫治疗中生物活性气体输送的最新进展
Pub Date : 2022-01-18 DOI: 10.1088/2516-1091/ac4c43
Yang Liu, Tiandong Chen, N. Gu, Fang Yang
Tumors with high mortality rates are still a major threat to human survival and health worldwide. In recent years, cancer immunotherapy has made rapid clinical progress in eliminating cancers by activating the host’s own immune system. Particularly, the use of physiological bioactive gas molecules such as nitric oxide, carbon monoxide and hydrogen sulfide have been developed as novel immunotherapeutic strategies. In this review, we have summarized the current strategies for antitumor immunotherapy via bioactive gas molecules, targeting delivery to the tumor microenvironment. We summarize the biofunctions of bioactive gases to the immune system, then gas delivery nanocarriers for antitumor immunotherapy and the current status of the platform are presented. Furthermore, since gas could specifically respond to the ultrasound, ultrasound-assisted gas delivery is generalized as a promising potential pathway for enhanced immunotherapy. Finally, we have discussed the challenges and opportunities for bioactive gas delivery and the effects of acoustic enhanced immunotherapy in future developments and possible clinical applications.
高死亡率的肿瘤仍然是全世界人类生存和健康的主要威胁。近年来,癌症免疫疗法通过激活宿主自身的免疫系统,在消除癌症方面取得了快速的临床进展。特别是,生理活性气体分子如一氧化氮、一氧化碳和硫化氢的使用已被开发为新的免疫治疗策略。在这篇综述中,我们总结了目前通过生物活性气体分子靶向递送到肿瘤微环境的抗肿瘤免疫治疗策略。我们总结了生物活性气体对免疫系统的生物功能,然后介绍了用于抗肿瘤免疫治疗的气体递送纳米载体和该平台的现状。此外,由于气体可以对超声产生特异性反应,超声辅助气体输送被认为是增强免疫治疗的一种有前途的潜在途径。最后,我们讨论了生物活性气体输送的挑战和机遇,以及声学增强免疫疗法在未来发展和可能的临床应用中的作用。
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引用次数: 0
Spike sorting: new trends and challenges of the era of high-density probes 尖峰分选:高密度探针时代的新趋势和挑战
Pub Date : 2022-01-07 DOI: 10.1088/2516-1091/ac6b96
A. P. Buccino, Samuel Garcia, P. Yger
Recording from a large neuronal population of neurons is a crucial challenge to unravel how information is processed by the brain. In this review, we highlight the recent advances made in the field of ‘spike sorting’, which is arguably a very essential processing step to extract neuronal activity from extracellular recordings. More specifically, we target the challenges faced by newly manufactured high-density multi-electrode array devices (HD-MEA), e.g. Neuropixels probes. Among them, we cover in depth the prominent problem of drifts (movements of the neurons with respect to the recording devices) and the current solutions to circumscribe it. In addition, we also review recent contributions making use of deep learning approaches for spike sorting, highlighting their advantages and disadvantages. Next, we highlight efforts and advances in unifying, validating, and benchmarking spike sorting tools. Finally, we discuss the spike sorting field in terms of its open and unsolved challenges, specifically regarding scalability and reproducibility. We conclude by providing our personal view on the future of spike sorting, calling for a community-based development and validation of spike sorting algorithms and fully automated, cloud-based spike sorting solutions for the neuroscience community.
从大量神经元群体中进行记录是解开大脑如何处理信息的关键挑战。在这篇综述中,我们强调了“尖峰分选”领域的最新进展,这可以说是从细胞外记录中提取神经元活动的一个非常重要的处理步骤。更具体地说,我们针对新制造的高密度多电极阵列器件(HD-MEA)所面临的挑战,例如Neuropixels探针。其中,我们深入讨论了漂移(神经元相对于记录设备的运动)的突出问题以及目前限制漂移的解决方案。此外,我们还回顾了最近利用深度学习方法进行尖峰排序的贡献,强调了它们的优缺点。接下来,我们将重点介绍在统一、验证和基准测试尖峰排序工具方面所做的努力和取得的进展。最后,我们讨论了尖峰排序领域的开放性和未解决的挑战,特别是在可扩展性和可再现性方面。最后,我们对尖峰排序的未来提出了个人观点,呼吁以社区为基础开发和验证尖峰排序算法,并为神经科学社区提供全自动、基于云的尖峰排序解决方案。
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引用次数: 15
Protein Based Biomaterials for Therapeutic and Diagnostic Applications. 用于治疗和诊断的蛋白质生物材料。
Pub Date : 2022-01-01 Epub Date: 2021-10-26 DOI: 10.1088/2516-1091/ac2841
Stanley Chu, Andrew L Wang, Aparajita Bhattacharya, Jin Kim Montclare

Proteins are some of the most versatile and studied macromolecules with extensive biomedical applications. The natural and biological origin of proteins offer such materials several advantages over their synthetic counterparts, such as innate bioactivity, recognition by cells and reduced immunogenic potential. Furthermore, proteins can be easily functionalized by altering their primary amino acid sequence and can often be further self-assembled into higher order structures either spontaneously or under specific environmental conditions. This review will feature the recent advances in protein-based biomaterials in the delivery of therapeutic cargo such as small molecules, genetic material, proteins, and cells. First, we will discuss the ways in which secondary structural motifs, the building blocks of more complex proteins, have unique properties that enable them to be useful for therapeutic delivery. Next, supramolecular assemblies, such as fibers, nanoparticles, and hydrogels, made from these building blocks that are engineered to behave in a cohesive manner, are discussed. Finally, we will cover additional modifications to protein materials that impart environmental responsiveness to materials. This includes the emerging field of protein molecular robots, and relatedly, protein-based theranostic materials that combine therapeutic potential with modern imaging modalities, including near-infrared fluorescence spectroscopy (NIRF), single-photo emission computed tomography/computed tomography (SPECT/CT), positron emission tomography (PET), magnetic resonance imaging (MRI), and ultrasound/photoacoustic imaging (US/PAI).

蛋白质是一些用途最广泛、研究最深入的大分子,具有广泛的生物医学应用。蛋白质的天然和生物来源为这些材料提供了比合成材料更大的优势,如天生的生物活性、细胞的识别能力和降低的免疫原性潜力。此外,蛋白质可以通过改变其伯氨基酸序列而容易地功能化,并且通常可以自发地或在特定的环境条件下进一步自组装成更高阶的结构。这篇综述将介绍基于蛋白质的生物材料在递送小分子、遗传物质、蛋白质和细胞等治疗货物方面的最新进展。首先,我们将讨论二级结构基序(更复杂蛋白质的构建块)具有独特特性的方式,使其能够用于治疗递送。接下来,讨论了由这些构建块制成的超分子组装体,如纤维、纳米颗粒和水凝胶,这些构建块被设计成以内聚的方式表现。最后,我们将介绍对蛋白质材料的额外修饰,这些修饰赋予材料环境响应性。这包括蛋白质分子机器人的新兴领域,以及将治疗潜力与现代成像模式相结合的基于蛋白质的治疗材料,包括近红外荧光光谱(NIRF)、单光子发射计算机断层扫描/计算机断层扫描(SPECT/CT)、正电子发射断层扫描(PET)、磁共振成像(MRI),以及超声/光声成像(US/PAI)。
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引用次数: 6
Effect of External Mechanical Stimuli on Human Bone: a narrative review. 外部机械刺激对人体骨骼的影响:一个叙述性的回顾。
Pub Date : 2022-01-01 Epub Date: 2022-01-10 DOI: 10.1088/2516-1091/ac41bc
Megan E Mancuso, Andrew R Wilzman, Kyle E Murdock, Karen L Troy

Bone is a living composite material that has the capacity to adapt and respond to both internal and external stimuli. This capacity allows bone to adapt its structure to habitual loads and repair microdamage. Although human bone evolved to adapt to normal physiologic loading (for example from gravitational and muscle forces), these same biological pathways can potentially be activated through other types of external stimuli such as pulsed electromagnetic fields, mechanical vibration, and others. This review summarizes what is currently known about how human bone adapts to various types of external stimuli. We highlight how studies on sports-specific athletes and other exercise interventions have clarified the role of mechanical loading on bone structure. We also discuss clinical scenarios, such as spinal cord injury, where mechanical loading is drastically reduced, leading to rapid bone loss and permanent alterations to bone structure. Finally, we highlight areas of emerging research and unmet clinical need.

骨是一种活的复合材料,具有适应和响应内外刺激的能力。这种能力使骨骼能够适应其结构以适应惯常的负荷并修复微损伤。虽然人类骨骼进化到适应正常的生理负荷(例如重力和肌肉力),但这些相同的生物途径可能通过其他类型的外部刺激(如脉冲电磁场、机械振动等)被激活。这篇综述总结了目前已知的人类骨骼如何适应各种类型的外部刺激。我们强调了对特定运动运动员和其他运动干预的研究如何阐明了机械载荷对骨结构的作用。我们还讨论了临床情况,例如脊髓损伤,其中机械负荷急剧减少,导致骨快速丢失和骨结构的永久性改变。最后,我们强调了新兴研究领域和未满足的临床需求。
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引用次数: 2
Wave-based optical coherence elastography: The 10-year perspective. 基于波的光学相干弹性成像:十年展望。
Pub Date : 2022-01-01 DOI: 10.1088/2516-1091/ac4512
Fernando Zvietcovich, Kirill V Larin

After 10 years of progress and innovation, optical coherence elastography (OCE) based on the propagation of mechanical waves has become one of the major and the most studied OCE branches, producing a fundamental impact in the quantitative and nondestructive biomechanical characterization of tissues. Preceding previous progress made in ultrasound and magnetic resonance elastography; wave-based OCE has pushed to the limit the advance of three major pillars: (1) implementation of novel wave excitation methods in tissues, (2) understanding new types of mechanical waves in complex boundary conditions by proposing advance analytical and numerical models, and (3) the development of novel estimators capable of retrieving quantitative 2D/3D biomechanical information of tissues. This remarkable progress promoted a major advance in answering basic science questions and the improvement of medical disease diagnosis and treatment monitoring in several types of tissues leading, ultimately, to the first attempts of clinical trials and translational research aiming to have wave-based OCE working in clinical environments. This paper summarizes the fundamental up-to-date principles and categories of wave-based OCE, revises the timeline and the state-of-the-art techniques and applications lying in those categories, and concludes with a discussion on the current challenges and future directions, including clinical translation research.

经过10年的发展和创新,基于机械波传播的光学相干弹性成像(OCE)已成为研究最多的主要分支之一,对组织的定量和无损生物力学表征产生了根本性的影响。超声和磁共振弹性成像的先前进展;基于波的OCE已经推动了三个主要支柱的进步:(1)在组织中实施新的波激发方法,(2)通过提出先进的分析和数值模型来理解复杂边界条件下的新型机械波,以及(3)开发能够检索定量的二维/三维组织生物力学信息的新型估计器。这一显著进展促进了在回答基础科学问题方面的重大进展,并改善了几种类型组织的医学疾病诊断和治疗监测,最终导致了临床试验和转化研究的首次尝试,旨在使基于波的OCE在临床环境中工作。本文总结了基于波浪的OCE的最新基本原理和类别,修订了时间表以及这些类别中最先进的技术和应用,最后讨论了当前的挑战和未来的方向,包括临床翻译研究。
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引用次数: 27
Ethical and social aspects of neural prosthetics 神经修复术的伦理和社会方面
Pub Date : 2021-10-26 DOI: 10.1088/2516-1091/ac23e6
W. Glannon
Neural prosthetics are devices or systems that bypass, modulate, supplement, or replace regions of the brain and its connections to the body that are damaged and dysfunctional from congenital abnormalities, brain and spinal cord injuries, limb loss, and neuropsychiatric disorders. Some prosthetics are implanted in the brain. Others consist of implants and systems outside the brain to which they are connected. Still others are completely external to the brain. But they all send inputs to and receive outputs from neural networks to modulate or improve connections between the brain and body. As artificial systems, neural prosthetics can improve but not completely restore natural sensory, motor and cognitive functions. This review examines the main ethical and social issues generated by experimental and therapeutic uses of seven types of neural prosthetics: auditory and visual prosthetics for deafness and blindness; deep brain stimulation for prolonged disorders of consciousness; brain-computer and brain-to-brain interfaces to restore movement and communication; memory prosthetics to encode and retrieve information; and optogenetics to modulate or restore neural function. The review analyzes and discusses how recipients of neural prosthetics can benefit from them in restoring autonomous agency, how they can be harmed by trying and failing to use or adapt to them, how these systems affect their identities, how to protect people with prosthetics from external interference, and how to ensure fair access to them. The review concludes by emphasizing the control these systems provide for people and a brief exploration of the future of neural prosthetics.
神经修复术是一种绕过、调节、补充或替代大脑及其与身体连接的区域的装置或系统,这些区域因先天性异常、脑和脊髓损伤、肢体丧失和神经精神障碍而受损和功能失调。一些假肢被植入大脑。其他包括植入物和大脑外的系统,它们与之相连。还有一些完全在大脑之外。但它们都向神经网络发送输入并从神经网络接收输出,以调节或改善大脑和身体之间的连接。作为人工系统,神经假肢可以改善但不能完全恢复自然的感觉、运动和认知功能。这篇综述审查了七种神经假肢的实验和治疗用途所产生的主要伦理和社会问题:耳聋和失明的听觉和视觉假肢;脑深部刺激治疗长期意识障碍;脑-计算机和脑-脑接口,以恢复运动和通信;记忆修复术,用于编码和检索信息;以及调节或恢复神经功能的光遗传学。该综述分析和讨论了神经假肢的接受者如何在恢复自主能动性方面从中受益,他们如何因尝试和不使用或适应神经假肢而受到伤害,这些系统如何影响他们的身份,如何保护使用假肢的人免受外部干扰,以及如何确保公平使用假肢。综述最后强调了这些系统为人们提供的控制,并对神经修复术的未来进行了简要探索。
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引用次数: 1
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Progress in biomedical engineering (Bristol, England)
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