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Active upper limb prostheses: a review on current state and upcoming breakthroughs. 主动上肢假体:现状及未来的突破
IF 7.7 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-01-06 DOI: 10.1088/2516-1091/acac57
Andrea Marinelli, Nicolò Boccardo, Federico Tessari, Dario Di Domenico, Giulia Caserta, Michele Canepa, Giuseppina Gini, Giacinto Barresi, Matteo Laffranchi, Lorenzo De Michieli, Marianna Semprini

The journey of a prosthetic user is characterized by the opportunities and the limitations of a device that should enable activities of daily living (ADL). In particular, experiencing a bionic hand as a functional (and, advantageously, embodied) limb constitutes the premise for promoting the practice in using the device, mitigating the risk of its abandonment. In order to achieve such a result, different aspects need to be considered for making the artificial limb an effective solution to accomplish ADL. According to such a perspective, this review aims at presenting the current issues and at envisioning the upcoming breakthroughs in upper limb prosthetic devices. We first define the sources of input and feedback involved in the system control (at user-level and device-level), alongside the related algorithms used in signal analysis. Moreover, the paper focuses on the user-centered design challenges and strategies that guide the implementation of novel solutions in this area in terms of technology acceptance, embodiment, and, in general, human-machine integration based on co-adaptive processes. We here provide the readers (belonging to the target communities of researchers, designers, developers, clinicians, industrial stakeholders, and end-users) with an overview of the state-of-the-art and the potential innovations in bionic hands features, hopefully promoting interdisciplinary efforts for solving current issues of upper limb prostheses. The integration of different perspectives should be the premise to a transdisciplinary intertwining leading to a truly holistic comprehension and improvement of the bionic hands design. Overall, this paper aims to move the boundaries in prosthetic innovation beyond the development of a tool and toward the engineering of human-centered artificial limbs.

义肢使用者的旅程的特点是机会和设备的局限性,应该使日常生活活动(ADL)。特别是,体验仿生手作为一个功能(并且,有利的是,具体化)肢体构成了促进使用该设备的实践的前提,减轻了其放弃的风险。为了达到这样的效果,需要考虑不同的方面,使假肢成为实现ADL的有效解决方案。基于这一观点,本文旨在介绍目前上肢假肢装置存在的问题,并展望未来的突破。我们首先定义了系统控制(用户级和设备级)中涉及的输入和反馈的来源,以及信号分析中使用的相关算法。此外,本文还重点介绍了以用户为中心的设计挑战和策略,这些挑战和策略指导了该领域在技术接受、实施以及基于共同适应过程的人机集成方面的新解决方案的实施。我们在这里为读者(属于研究人员、设计师、开发人员、临床医生、工业利益相关者和最终用户的目标群体)提供了仿生手特征的最新技术和潜在创新的概述,希望促进跨学科的努力来解决当前上肢假肢的问题。不同观点的整合应该是跨学科相互交织的前提,从而真正全面地理解和改进仿生手的设计。总体而言,本文旨在将假肢创新的界限从工具的开发转向以人为中心的假肢工程。
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引用次数: 0
The potential synergies between synthetic data and in silico trials in relation to generating representative virtual population cohorts 合成数据和计算机试验在产生具有代表性的虚拟人群队列方面的潜在协同作用
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-01-03 DOI: 10.1088/2516-1091/acafbf
P. Myles, Johan Ordish, A. Tucker
In silico trial methods promise to improve the path to market for both medicines and medical devices, targeting the development of products, reducing reliance on animal trials, and providing adjunct evidence to bolster regulatory submissions. In silico trials are only as good as the simulated data which underpins them, consequently, often the most difficult challenge when creating robust in silico models is the generation of simulated measurements or even virtual patients that are representative of real measurements and patients. This article digests the current state of the art for generating synthetic patient data outside the context of in silico trials and outlines potential synergies to unlock the potential of in silico trials using virtual populations, by exploiting synthetic patient data to model effects on a more diverse and representative population. Synthetic data could be defined as artificial data that mimic the properties and relationships in real data. Recent advances in synthetic data generation methodologies have allowed for the generation of high-fidelity synthetic data that are both statistically and clinically, indistinguishable from real patient data. Other experimental work has demonstrated that synthetic data generation methods can be used for selective sample boosting of underrepresented groups. This article will provide a brief outline of synthetic data generation approaches and discuss how evaluation frameworks developed to assess synthetic data fidelity and utility could be adapted to evaluate the similarity of virtual patients used for in silico trials, to real patients. The article will then discuss outstanding challenges and areas for further research that would advance both synthetic data generation methods and in silico trial methods. Finally, the article will also provide a perspective on what evidence will be required to facilitate wider acceptance of in silico trials for regulatory evaluation of medicines and medical devices, including implications for post marketing safety surveillance.
计算机试验方法有望改善药品和医疗器械的上市途径,以产品开发为目标,减少对动物试验的依赖,并提供辅助证据,以支持提交监管文件。计算机试验的效果与支持它们的模拟数据一样好,因此,在创建健壮的计算机模型时,最困难的挑战通常是生成模拟测量结果,甚至是代表真实测量结果和患者的虚拟患者。本文概述了在计算机试验环境之外生成合成患者数据的最新技术,并概述了利用虚拟人群来释放计算机试验潜力的潜在协同作用,方法是利用合成患者数据对更多样化和更具代表性的人群进行建模。合成数据可以定义为模拟真实数据中的属性和关系的人工数据。合成数据生成方法的最新进展已经允许生成高保真的合成数据,这些数据在统计和临床方面都与真实的患者数据无法区分。其他实验工作已经证明,合成数据生成方法可以用于选择性样本增强代表性不足的群体。本文将简要概述合成数据生成方法,并讨论如何开发评估框架来评估合成数据的保真度和实用性,以评估用于计算机试验的虚拟患者与真实患者的相似性。然后,文章将讨论突出的挑战和进一步研究的领域,这将推进合成数据生成方法和硅试验方法。最后,本文还将提供一个视角,说明需要哪些证据来促进更广泛地接受用于药品和医疗器械监管评估的计算机试验,包括对上市后安全监督的影响。
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引用次数: 4
A perspective on electroencephalography sensors for brain-computer interfaces 脑机接口用脑电图传感器研究进展
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-10-11 DOI: 10.1088/2516-1091/ac993d
F. Iacopi, Chin-Teng Lin
This Perspective offers a concise overview of the current, state-of-the-art, neural sensors for brain-machine interfaces, with particular attention towards brain-controlled robotics. We first describe current approaches, decoding models and associated choice of common paradigms, and their relation to the position and requirements of the neural sensors. While implanted intracortical sensors offer unparalleled spatial, temporal and frequency resolution, the risks related to surgery and post-surgery complications pose a significant barrier to deployment beyond severely disabled individuals. For less critical and larger scale applications, we emphasize the need to further develop dry scalp electroencephalography (EEG) sensors as non-invasive probes with high sensitivity, accuracy, comfort and robustness for prolonged and repeated use. In particular, as many of the employed paradigms require placing EEG sensors in hairy areas of the scalp, ensuring the aforementioned requirements becomes particularly challenging. Nevertheless, neural sensing technologies in this area are accelerating thanks to the advancement of miniaturised technologies and the engineering of novel biocompatible nanomaterials. The development of novel multifunctional nanomaterials is also expected to enable the integration of redundancy by probing the same type of information through different mechanisms for increased accuracy, as well as the integration of complementary and synergetic functions that could range from the monitoring of physiological states to incorporating optical imaging.
本展望提供了当前最先进的脑机接口神经传感器的简要概述,特别关注脑控制机器人。我们首先描述了当前的方法、解码模型和相关的通用范式选择,以及它们与神经传感器的位置和要求的关系。虽然植入的皮质内传感器提供了无与伦比的空间、时间和频率分辨率,但与手术和术后并发症相关的风险对严重残疾人群以外的应用构成了重大障碍。对于不那么关键和大规模的应用,我们强调需要进一步开发干性头皮脑电图(EEG)传感器作为非侵入性探针,具有高灵敏度,准确性,舒适性和耐用性,适合长时间和重复使用。特别是,由于许多使用的范例需要将EEG传感器放置在头皮的毛发区域,因此确保上述要求变得特别具有挑战性。然而,由于微型化技术的进步和新型生物相容性纳米材料的工程,这一领域的神经传感技术正在加速发展。新型多功能纳米材料的开发也有望通过不同机制探测相同类型的信息来提高准确性,从而实现冗余的整合,以及从生理状态监测到结合光学成像的互补和协同功能的整合。
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引用次数: 3
Polyaniline based polymers in tissue engineering applications: a review 聚苯胺基聚合物在组织工程中的应用综述
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-09-21 DOI: 10.1088/2516-1091/ac93d3
R. Rai, J. Roether, A. Boccaccini
A number of electrically conducting polymers, such as polyaniline (PANi), as well as functionalized aniline copolymers and composites, which are simultaneously biodegradable and conductive, have been applied for developing electrically conductive scaffolds for tissue engineering (TE) in recent years. The rationale behind these scaffolds is to induce ‘electroactivity’ in scaffolds, as many research works have shown that an intrinsic electrical activity leads to both increased regeneration rates and improved healing of damaged tissues. PANi is the conductive polymer of choice because it is economical and easy to process with a variety of methods. The resultant PANi based biomaterials have shown biocompatibility, conductivity, suitable processability, positive cellular response, as well as an intrinsic antibacterial effect in numerous research studies. The analysis of the literature has revealed that PANi based scaffolds have been investigated for TE applications including skin/wound healing, bone, cartilage, nerve/spinal cord, vascular, skeletal muscle repair and for the treatment of infertility. Although PANi based materials find widespread applications in other sectors, they are still far away from being commercially exploited as scaffolds for TE despite positive research results. This review aims to discuss and critically assess the current state of PANi based TE scaffolds for different applications. A future perspective for utilizing PANi based biomaterials for applications in TE is discussed, including recent considerations about potential cytotoxic effects.
近年来,聚苯胺(PANi)、功能化苯胺共聚物及复合材料等具有生物可降解性和导电性的导电聚合物被广泛应用于组织工程(TE)导电支架的研制。这些支架背后的原理是在支架中诱导“电活动”,因为许多研究工作表明,固有的电活动既可以提高再生速度,又可以改善受损组织的愈合。聚苯胺是导电聚合物的首选,因为它经济且易于用多种方法加工。由此得到的聚苯胺基生物材料在许多研究中显示出生物相容性、导电性、适宜的可加工性、积极的细胞反应以及固有的抗菌作用。文献分析显示,聚苯胺基支架已被研究用于TE的应用,包括皮肤/伤口愈合、骨、软骨、神经/脊髓、血管、骨骼肌修复和不孕症的治疗。尽管聚苯胺基材料在其他领域得到了广泛的应用,但尽管取得了积极的研究成果,但它们距离作为TE支架进行商业开发还很遥远。本文旨在讨论和批判性地评估聚苯胺基TE支架在不同应用中的现状。讨论了利用聚苯胺基生物材料在TE中的应用的未来前景,包括最近对潜在细胞毒性作用的考虑。
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引用次数: 7
Locomotor adaptations: paradigms, principles and perspectives 运动适应:范例、原则和观点
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-09-13 DOI: 10.1088/2516-1091/ac91b6
G. Severini, M. Zych
The term ‘locomotor adaptations’ (LMA) indicates the alteration in motor commands that is automatically or volitionally generated in response to a perturbation continuously altering the task demands of locomotion. LMAs have been widely studied, using a variety of experimental paradigms and analysis techniques. The perturbation can be expected or unexpected and constituted by a change in the movement environment, by forces actively pushing the person’s body segments, by a modification in the sensory feedback associated with the task or by explicit task instructions. The study of LMAs has been key in widening our understanding of the principles regulating bipedal locomotion, from the overall strategies driving the short-term adjustments of motor commands, down to the different neural circuits involved in the different aspects of locomotion. In this paper we will provide an in-depth review of the research field of LMAs. We will start with an analysis of the principles driving the evolution of bipedal locomotion in humans. Then we will review the different experimental paradigms that have been used to trigger LMAs. We will analyze the evidence on the neurophysiological correlates of adaptation and the behavioral reasons behind it. We will then discuss the characteristics of LMA such as transfer, generalization, and savings. This will be followed by a critical analysis of how different studies point to different task-goal related drivers of adaptation. Finally, we will conclude with a perspective on the research field of LMAs and on its ramifications in neuroscience and rehabilitation.
术语“运动适应”(LMA)表示运动命令的改变,该改变是响应于不断改变运动任务需求的扰动而自动或自愿产生的。LMA已经被广泛研究,使用了各种实验范式和分析技术。扰动可以是预期的或出乎意料的,并且由运动环境的变化、主动推动人的身体部位的力、与任务相关的感觉反馈的修改或明确的任务指令构成。LMA的研究是拓宽我们对调节两足动物运动原理的理解的关键,从驱动运动命令短期调整的整体策略,到运动不同方面涉及的不同神经回路。在本文中,我们将对LMA的研究领域进行深入的综述。我们将从分析驱动人类两足运动进化的原理开始。然后,我们将回顾用于触发LMA的不同实验范式。我们将分析适应的神经生理学相关性及其背后的行为原因的证据。然后我们将讨论LMA的特征,如转移、泛化和储蓄。接下来将对不同的研究如何指向不同的任务目标相关的适应驱动因素进行批判性分析。最后,我们将对LMA的研究领域及其在神经科学和康复中的影响进行展望。
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引用次数: 2
Photosymbiotic tissue engineering and regeneration. 光共生组织工程与再生
IF 7.7 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-09-06 DOI: 10.1088/2516-1091/ac8a2f
Sushila Maharjan, Diana Priscills Bonilla-Ruelas, Gorka Orive, Yu Shrike Zhang

As the field of tissue engineering and regenerative medicine progresses, the possibility for artificial organs to restore normal tissue functions seems to become more feasible. However, a major challenge in the long-term culture of the engineered tissues is the lack of adequate oxygenation. The photosynthetic supply of oxygen (O2) for tissues and organs using photoautotrophic microorganisms has been explored recently in bothin vitroandin vivostudies. The biofabrication of photosymbiotic scaffolds using biomaterials, photosynthetic microorganisms, and human cells has shown constant generation of O2in response to light illumination while avoiding hypoxic conditions. This emerging strategy of photosymbiotic oxygenation is potentially an attractive approach to overcome the need of adequate oxygenation in tissue engineering and regenerative medicine. This Perspective aims to present an overview on the applications of photoautotrophic microorganism-enabled oxygenation strategies for overcoming hypoxia-related challenges in tissue engineering and regenerative medicine.

随着组织工程和再生医学领域的发展,人工器官恢复正常组织功能的可能性似乎变得更加可行。然而,工程组织的长期培养中的一个主要挑战是缺乏足够的氧合。最近,在体外和体内研究中,都对利用光自养微生物为组织和器官提供光合氧气(O2)进行了探索。使用生物材料、光合微生物和人类细胞的光共生支架的生物制造表明,在避免缺氧条件的同时,光照会不断产生O2。这种新兴的光共生氧合策略可能是一种有吸引力的方法,可以克服组织工程和再生医学中对充分氧合的需求。该观点旨在概述光自养微生物氧合策略在组织工程和再生医学中克服缺氧相关挑战的应用。
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引用次数: 0
Immunocompetent brain organoids—microglia enter the stage 具有免疫能力的脑类器官-小胶质细胞进入发育阶段
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-08-30 DOI: 10.1088/2516-1091/ac8dcf
Sònia Sabaté-Soler, M. Bernini, J. Schwamborn
Microglia, the immune cells of the brain, are a focus of studies in neurodegenerative diseases. Similarly, research about induced pluripotent stem cell (iPSC)-derived whole brain and region-specific organoids is increasing. In organoids, the complexity of the culture systems increases, mimicking better the actual scenario in the human brain. Furthermore, animal models do not always recapitulate human neurodegeneration, and they imply more ethical concerns compared to organoid systems. Recently the integration of iPSC-derived microglia into brain organoids has been achieved, and on-chip technologies have been focusing on microglia interaction with neural cells. In this review, we discuss the achievements on integrating microglia into brain organoids. We study the cell organization, ultrastructure and cell signalling of microglia with respect to other cell types in organoids as well as their functionality in the system. A particular focus here is on the interaction with the midbrain and dopaminergic systems. Finally, we discuss the achievements until now concerning neuroinflammation and disease modelling, and the possible therapeutic approaches targeting microglia and neuroinflammation in 3D systems.
小胶质细胞是大脑的免疫细胞,是神经退行性疾病研究的焦点。同样,关于诱导多能干细胞(iPSC)衍生的全脑和区域特异性类器官的研究也在增加。在类器官中,培养系统的复杂性增加,更好地模仿人类大脑中的实际情况。此外,动物模型并不总是概括人类神经变性,与类器官系统相比,它们意味着更多的伦理问题。近年来,ipsc衍生的小胶质细胞已被整合到脑类器官中,芯片技术已将重点放在小胶质细胞与神经细胞的相互作用上。本文就小胶质细胞融入脑类器官的研究进展作一综述。我们研究了小胶质细胞的细胞组织、超微结构和细胞信号传导,以及它们在类器官中其他细胞类型的功能。这里特别关注的是与中脑和多巴胺能系统的相互作用。最后,我们讨论了迄今为止关于神经炎症和疾病建模的成就,以及在3D系统中针对小胶质细胞和神经炎症的可能治疗方法。
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引用次数: 1
Advances in engineered exosomes towards cancer diagnosis and therapeutics. 工程外泌体在癌症诊断和治疗中的研究进展
IF 7.7 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-08-05 DOI: 10.1088/2516-1091/ac73c9
Tanziela Tanziela, Xiawei Dong, Jing Ye, Zengchao Guo, Hui Jiang, Zuhong Lu, Xiaohui Liu, Xuemei Wang

Exosomes have emerged as natural nanocarriers and are advantageous in the field of nanomedicine due to their lipid bilayer membrane comprising many proteins, nucleic acids and cell debris. Exosomes are secreted from all types of living cells and play a role in cancer diagnosis and therapy because of their biological properties, such as intercellular communication, modulation of immune responses, biocompatibility and target specificity. Many studies have shown that exosomes can be engineered or modified with different therapeutic substances, including nucleic acids, proteins, drugs and other nanomaterials, to improve their specificity, efficiency and safety in nanomedicine. In this review, we summarize the methodologies of exosome biogenesis, purification, the possible mechanisms of cellular uptake and the important role of exosomes in cancer diagnosis, followed by the role of engineered exosomes in cancer therapy. Also, future trends and challenges are discussed. We strongly suggest that a clear articulation of the fundamental principles for the creation of exosome-based theranostic platforms will help reveal the unique powers of exosomes in early cancer diagnosis and therapeutics, including chemotherapy, gene therapy, immunotherapy and phototherapy.

外泌体已作为天然纳米载体出现,并且由于其包含许多蛋白质、核酸和细胞碎片的脂质双层膜而在纳米医学领域具有优势。外泌体是由所有类型的活细胞分泌的,由于其生物学特性,如细胞间通讯、免疫反应的调节、生物相容性和靶点特异性,在癌症的诊断和治疗中发挥作用。许多研究表明,外泌体可以用不同的治疗物质进行工程或修饰,包括核酸、蛋白质、药物和其他纳米材料,以提高其在纳米医学中的特异性、效率和安全性。在这篇综述中,我们总结了外泌体的生物发生、纯化、细胞摄取的可能机制以及外泌体在癌症诊断中的重要作用,以及工程外泌体对癌症治疗的作用。此外,还讨论了未来的趋势和挑战。我们强烈建议,明确阐明创建基于外泌体的治疗平台的基本原则将有助于揭示外泌体在癌症早期诊断和治疗中的独特力量,包括化疗、基因治疗、免疫疗法和光疗。
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引用次数: 0
Cancer-on-chip technology: current applications in major cancer types, challenges and future prospects. 癌症芯片技术:目前在主要癌症类型中的应用、挑战和未来展望
IF 7.7 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-08-01 DOI: 10.1088/2516-1091/ac8259
Zakaria Baka, Marie Stiefel, Agathe Figarol, Claire Godier, Abhik Mallick, Olivier Joubert, Nureddin Ashammakhi, Eric Gaffet, Halima Alem

Conventional 2D cell cultures are widely used for the development of new anticancer drugs. However, their relevance asin vitromodels is increasingly questioned as they are considered too simplistic compared to complex, three-dimensionalin vivotumors. Moreover, animal experiments are not only costly and time-consuming, but also raise ethical issues and their use for some applications has been restricted. Therefore, it becomes crucial to develop new experimental models that better capture the complexity and dynamic aspects ofin vivotumors. New approaches based on microfluidic technology are promising. This technology has indeed been used to create microphysiological systems called 'organ-on-chip' which simulate key structural and functional features of human tissues and organs. These devices have further been adapted to create cancer models giving rise to the 'cancer-on-chip' (COC) concept. In this review, we will discuss the main COC models described so far for major cancer types including lung, prostate, breast, colorectal, pancreatic, and ovarian cancers. Then, we will highlight the challenges that this technology is facing and the possible research perspectives that can arise from them.

传统的二维细胞培养被广泛用于开发新的抗癌药物。然而,它们作为体外模型的相关性越来越受到质疑,因为与复杂的、三维的体内肿瘤相比,它们被认为过于简单。此外,动物实验不仅成本高、耗时长,而且还会引发伦理问题,在某些应用上的使用受到限制。因此,开发新的实验模型以更好地捕捉体内肿瘤的复杂性和动态方面变得至关重要。基于微流体技术的新方法是有前景的。这项技术确实已被用于制造被称为“器官芯片”的微生理系统,该系统可以模拟人体组织和器官的关键结构和功能特征。这些设备进一步被用于创建癌症模型,从而产生了“芯片上的癌症”(COC)概念。在这篇综述中,我们将讨论迄今为止描述的主要癌症类型的主要COC模型,包括肺癌、前列腺癌、乳腺癌、结肠直肠癌、胰腺癌和卵巢癌。然后,我们将强调该技术面临的挑战以及可能由此产生的研究前景。
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引用次数: 0
A review on interaction control for contact robots through intent detection 基于意图检测的接触机器人交互控制综述
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-07-15 DOI: 10.1088/2516-1091/ac8193
Yanan Li, Aran Sena, Ziwei Wang, Xueyan Xing, J. Babič, E. V. van Asseldonk, E. Burdet
Interaction control presents opportunities for contact robots physically interacting with their human user, such as assistance targeted to each human user, communication of goals to enable effective teamwork, and task-directed motion resistance in physical training and rehabilitation contexts. Here we review the burgeoning field of interaction control in the control theory and machine learning communities, by analysing the exchange of haptic information between the robot and its human user, and how they share the task effort. We first review the estimation and learning methods to predict the human user intent with the large uncertainty, variability and noise and limited observation of human motion. Based on this motion intent core, typical interaction control strategies are described using a homotopy of shared control parameters. Recent methods of haptic communication and game theory are then presented to consider the co-adaptation of human and robot control and yield versatile interactive control as observed between humans. Finally, the limitations of the presented state of the art are discussed and directions for future research are outlined.
交互控制为接触式机器人与其人类用户进行物理交互提供了机会,例如针对每个人类用户的帮助、实现有效团队合作的目标沟通,以及在体能训练和康复环境中针对任务的运动阻力。在这里,我们通过分析机器人和人类用户之间的触觉信息交换,以及他们如何分担任务,回顾了控制理论和机器学习社区中新兴的交互控制领域。我们首先回顾了预测人类用户意图的估计和学习方法,这些方法具有很大的不确定性、可变性和噪声,并且对人类运动的观察有限。基于该运动意图核心,利用共享控制参数的同伦论描述了典型的交互控制策略。然后提出了触觉通信和博弈论的最新方法,以考虑人和机器人控制的协同适应,并产生人与人之间观察到的多功能交互式控制。最后,讨论了现有技术的局限性,并概述了未来研究的方向。
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引用次数: 11
期刊
Progress in biomedical engineering (Bristol, England)
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