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The advantages of microneedle patches compared to conventional needle-based drug delivery and biopsy devices in medicine 微针贴片与传统针式给药和活检设备相比在医学上的优势
Pub Date : 2024-06-03 DOI: 10.1016/j.bea.2024.100127
Alissa Reinke , Eliza J Whiteside , Louisa Windus , Devang Desai , Emma Stehr , Zahra Faraji Rad

Microneedle (MN) patches are composed of micron-sized needles organised in arrays and attached to the backing of a patch. The most common type is the transdermal patch, designed to uniformly penetrate the stratum corneum to reach the dermis of the skin. Recent advances in 3D printing technology have allowed the development of reproducible, efficient methods to create microneedles on a large scale, which had previously been a factor in the limited clinical uptake. In comparison to conventional drug delivery methods, MN patches have been shown to significantly reduce pain and scar generation while maintaining effective and reliable delivery of vaccines, immunotherapies, and slow-release drug therapies. The MN design has also been investigated as an alternative to conventional tissue biopsy, with positive results. Synchronous delivery of medications while monitoring biomarkers in dermal interstitial fluid (ISF) is also a promising clinical development with wide-reaching benefits. MNs are diverse in design and material composition, and with developments in fabrication technology, transdermal drug delivery has been applied to many clinical fields, including chronic illnesses such as arthritis or diabetes, cancer, immunotherapies, epidemic disease prevention and ocular treatments. While the majority of MN patch applications are still in the pre-clinical testing phase in animal models, further translation of this technology to the clinic could aid in medication and vaccine compliance, improve treatment access in rural and remote communities, improve targeted therapy applications and provide financial cost savings to the public health sector. This review evaluates the designs and applications of current transdermal MN patches for drug delivery, biomarker monitoring and diagnostic biopsies compared to conventional needle-based methods.

微针(MN)贴片是由微米大小的针组成的阵列,并附在贴片的背面。最常见的类型是透皮贴片,旨在均匀地穿透角质层到达皮肤真皮层。三维打印技术的最新进展使得可重复、高效地大规模制造微针的方法得以发展,而这曾是临床应用有限的一个因素。与传统给药方法相比,微针贴片已被证明能显著减少疼痛和疤痕的产生,同时保持疫苗、免疫疗法和缓释药物疗法的有效可靠给药。MN 设计还被研究用于替代传统的组织活检,并取得了积极的成果。在监测真皮层间液(ISF)中生物标志物的同时同步给药也是一项前景广阔的临床开发,具有广泛的益处。MN 的设计和材料成分多种多样,随着制造技术的发展,透皮给药已应用于许多临床领域,包括关节炎或糖尿病等慢性疾病、癌症、免疫疗法、流行病预防和眼部治疗。虽然大多数 MN 贴片的应用仍处于动物模型的临床前测试阶段,但将这种技术进一步转化到临床中,可以帮助人们遵守用药和接种疫苗的规定,改善农村和偏远社区的治疗条件,改进靶向治疗的应用,并为公共卫生部门节约成本。本综述评估了目前用于给药、生物标记物监测和诊断性活检的透皮 MN 贴片的设计和应用,并与传统的针式方法进行了比较。
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引用次数: 0
Validation of upper extremity kinematics using Markerless motion capture 利用无标记运动捕捉验证上肢运动学
Pub Date : 2024-06-01 DOI: 10.1016/j.bea.2024.100128
Robyn M. Hansen, Sara L. Arena, Robin M. Queen

Movement research has typically been performed using three-dimensional (3D) marker-based motion capture, which is considered the “gold-standard” for biomechanical assessment. However, limitations exist due to the lack of portability, extensive preparation for data collection, marker placement training, error due to marker movement, and possible skin irritation due to marker adhesives. There is inherent error due to motion artifact stemming from skin movement and differences in marker placement between testers. Markerless motion capture systems are emerging as a new method of kinematic assessment. These methods require little preparation and there is no need to alter participant clothing. Markerless motion capture has also been validated for the lower extremity in healthy older adults during gait. However, it has not been validated for other populations or for the assessment of upper extremity (UE) motion. Therefore, the purpose of this study was to examine differences in calculated UE kinematics between marker-based and a markerless motion capture system. Participants attended two data collection sessions. Marker-based and markerless motion capture data was collected simultaneously while participants completed the Box and Blocks test (BBT). Kinematic and spatiotemporal data from both systems was exported using identical time series to ensure the same conditions for comparisons. Intraclass Correlation Coefficients (ICCs) were calculated to determine between session reliability for both systems on range of motion and peak joint angular data to ensure movement variability was not affecting measurement consistency. ICCs and Bland Altman statistics were also calculated between the systems. Root mean square deviation (RMSD) values were determined between demeaned UE joint angles for the two systems to examine movement pattern differences. The resulting between-session ICCs for each system showed that the markerless system shared similar reliability during this task as the marker-based system, further supporting the effect of variability on between-session reliability. Between-system ICCs resulted in good (0.7<ICC<0.9) to excellent (ICC>0.9) agreement. Bland Altman results confirmed the existence of measurement bias between the systems. RMSD values for all UE joint angles were found to be less than 6°. Overall, the results from this study support the use of markerless motion capture in clinical settings to examine upper extremity biomechanics in children.

运动研究通常使用基于三维(3D)标记的运动捕捉来进行,这被认为是生物力学评估的 "黄金标准"。然而,由于缺乏便携性、数据采集前的大量准备工作、标记放置训练、标记移动造成的误差以及标记粘合剂可能对皮肤造成的刺激等原因,这种方法存在局限性。由于皮肤运动造成的运动伪影和测试者之间标记位置的差异,会产生固有误差。无标记运动捕捉系统正在成为一种新的运动学评估方法。这些方法几乎不需要准备工作,也不需要改变参与者的服装。无标记运动捕捉也已在健康老年人的下肢步态中得到验证。然而,该方法尚未在其他人群或上肢(UE)运动评估中得到验证。因此,本研究的目的是考察基于标记和无标记运动捕捉系统计算出的上肢运动学数据之间的差异。参与者参加了两个数据采集环节。基于标记和无标记的运动捕捉数据是在受试者完成 "方块测试"(BBT)时同时采集的。两个系统的运动学和时空数据均使用相同的时间序列导出,以确保在相同条件下进行比较。通过计算类内相关系数(ICC)来确定两套系统在运动范围和关节角度峰值数据上的疗程间可靠性,以确保运动变异性不会影响测量的一致性。还计算了两个系统之间的 ICC 和 Bland Altman 统计量。两个系统的去均方根偏差 (RMSD) 值被确定在去均方根 UE 关节角度之间,以检查运动模式的差异。结果显示,无标记系统与有标记系统在这项任务中的可靠性相似,这进一步证明了变异性对不同系统间可靠性的影响。系统间 ICC 的一致性从良好(0.7<ICC<0.9)到优秀(ICC>0.9)不等。Bland Altman 结果证实了系统间存在测量偏差。所有 UE 关节角度的 RMSD 值均小于 6°。总之,这项研究的结果支持在临床环境中使用无标记运动捕捉来检查儿童上肢生物力学。
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引用次数: 0
Unveiling the intricacies of protein-protein interactions and membrane fouling: Exploring hetero-protein complex formation in binary mixtures 揭开蛋白质-蛋白质相互作用和膜堵塞的神秘面纱:探索二元混合物中异种蛋白复合物的形成
Pub Date : 2024-05-29 DOI: 10.1016/j.bea.2024.100129
Majak Mapiour , Amira Abdelrasoul

In practical applications, protein fouling studies often face limitations due to their reliance on single-protein feed experiments. It is crucial to acknowledge that interprotein interactions can significantly differ from intraprotein interactions, leading to variations in adsorption and membrane fouling behaviors. In this review, we delve into the dynamics of adsorption and membrane fouling, with a specific focus on single and binary solutions of Bovine Serum Albumin (BSA) and Lysozyme (LYZ) at or near physiological pH. These two proteins differ in terms of size, charge, and conformational stability, allowing for comparisons between small and large proteins, positively and negatively charged proteins, as well as rigid and flexible proteins. To gain further insights, we compare the findings from LYZ in single and binary solutions with those of alpha lactalbumin (α-LA), which, despite having opposite charges, shares a similar size with LYZ. The formation of BSA-LYZ heteroprotein complexes may introduce unique fouling trends in binary solutions compared to single solutions. This interplay can either enhance, reduce, or leave fouling unaffected. While studies employing the Extended DLVO (Derjaguin, Landau, Vervey, and Overbeek) theory to predict fouling in protein mixtures are limited, preliminary investigations using DLVO show promise. This approach has the potential to extend to binary and multi-protein feeds, providing valuable insights into the dynamics of fouling behavior in complex protein solutions. Considering that BSA is often used as a surrogate for Human Serum Albumin (HSA), the findings of this endeavor hold particular significance. HSA ranks the most abundant plasma proteins and, therefore, represents a crucial subject in numerous protein-related studies.

在实际应用中,蛋白质污垢研究往往由于依赖单一蛋白质进料实验而面临限制。必须承认,蛋白质之间的相互作用可能与蛋白质内部的相互作用有很大不同,从而导致吸附和膜堵塞行为的变化。在这篇综述中,我们将深入研究吸附和膜堵塞的动态,特别关注生理 pH 值或接近生理 pH 值的牛血清白蛋白(BSA)和溶菌酶(LYZ)的单一和二元溶液。这两种蛋白质在大小、电荷和构象稳定性方面存在差异,因此可以对小蛋白和大蛋白、带正电和负电的蛋白以及刚性蛋白和柔性蛋白进行比较。为了获得更深入的见解,我们将 LYZ 在单溶液和二元溶液中的发现与α-乳白蛋白(α-LA)的发现进行了比较,后者尽管电荷相反,但大小与 LYZ 相似。与单一溶液相比,BSA-LYZ 杂蛋白复合物的形成可能会在二元溶液中产生独特的堵塞趋势。这种相互作用可以增强、减少或使污垢不受影响。虽然采用扩展 DLVO(Derjaguin、Landau、Vervey 和 Overbeek)理论来预测蛋白质混合物污垢的研究还很有限,但使用 DLVO 进行的初步研究显示了前景。这种方法有可能扩展到二元和多元蛋白质进料,为了解复杂蛋白质溶液中的污垢行为动态提供宝贵的见解。考虑到 BSA 经常被用作人血清白蛋白 (HSA) 的替代物,这项研究的发现具有特别重要的意义。HSA 是血浆中含量最高的蛋白质,因此是众多蛋白质相关研究中的重要课题。
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引用次数: 0
Cosmetic gloves from natural rubber latex for upper limb prostheses: Preparation and physicochemical, mechanical and biological characterization 上肢假肢用天然橡胶乳胶化妆手套:制备及物理化学、机械和生物学特性分析
Pub Date : 2024-05-18 DOI: 10.1016/j.bea.2024.100126
Danielle Restelatto , Jordana Bortoluz , Paula Sartori , Nayrim B. Guerra , Cristiani C.P. Cid , Robinson C.D. Cruz , Noel M. Gately , Declan M. Devine , Marcelo Giovanela , Mariana Roesch-Ely , Janaina S. Crespo

Upper limb amputations are frequently the result of traumatic events, often associated with car accidents or incidents involving industrial machinery. The development of prosthetic technologies is essential to provide physical assistance to amputees and offer psychological support. In such circumstances, cosmetic gloves can be utilized to improve personal and social comfort by enhancing visual characteristics similar to those of a biological hand. In this work, we developed formulations based on natural rubber latex (NRL) with antibacterial properties by the incorporation of an additive consisting of zinc oxide coated with silver nanoparticles to manufacture cosmetic gloves designed for upper limb prostheses. The dispersion efficiency of the additive was investigated by microscopic techniques. Tensile and tear strength tests, Shore A hardness measurements, swelling indices, hydrophobicity and inhibition of bacterial growth were also conducted to ascertain the suitability and adaptability of the developed material for integration into the daily activities of patients. Moreover, processing parameters for the immersion molding production of cosmetic gloves were assessed and validated, highlighting the crucial relationship between manufacturing techniques and material properties. Overall, the results indicated that the combination of the additive with a high crosslinking density of NRL effectively improved the material mechanical properties, resulting in a tensile strength of up to 20.7 MPa and a tear strength of approximately 40 kN m−1. In addition, and according to the antibacterial tests, the gloves exhibited bacteriostatic effects against Staphylococcus aureus and bactericidal effects against Escherichia coli. As a conclusion, the dataset indicates that the manufactured cosmetic gloves can be used to covering upper limb prostheses. Additionally, it underscores the considerable potential for the cosmetic glove manufacturing industry through the use of appropriate formulations and processing techniques for NRL.

上肢截肢往往是创伤事件造成的,通常与车祸或涉及工业机械的事故有关。假肢技术的发展对于为截肢者提供身体上的帮助和心理上的支持至关重要。在这种情况下,可以利用化妆手套来增强与生物手相似的视觉特征,从而提高个人和社会的舒适度。在这项工作中,我们在天然橡胶乳胶(NRL)的基础上开发了具有抗菌特性的配方,并在其中加入了一种由氧化锌和纳米银颗粒组成的添加剂,用于制造上肢假肢用化妆手套。通过显微技术研究了添加剂的分散效率。此外,还进行了拉伸和撕裂强度测试、邵氏 A 硬度测量、膨胀指数、疏水性和细菌生长抑制,以确定所开发材料的适用性和适应性,以便将其融入患者的日常活动中。此外,还评估并验证了用于浸泡成型生产化妆手套的加工参数,突出了生产技术与材料特性之间的重要关系。总之,研究结果表明,将添加剂与高交联密度的 NRL 结合使用,可有效改善材料的机械性能,使拉伸强度高达 20.7 兆帕,撕裂强度约为 40 kN m-1。此外,根据抗菌测试,手套对金黄色葡萄球菌具有抑菌作用,对大肠杆菌具有杀菌作用。总之,数据集表明,制造的化妆手套可用于覆盖上肢假肢。此外,通过使用适当的配方和 NRL 加工技术,它还强调了化妆手套制造业的巨大潜力。
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引用次数: 0
Design and development of a cost-effective portable IoT enabled multi-channel physiological signal monitoring system 设计和开发具有成本效益的便携式物联网多通道生理信号监测系统
Pub Date : 2024-05-13 DOI: 10.1016/j.bea.2024.100124
Samit Hasan , Tanvir Pantha, Muhammad Abdullah Arafat

In health care, early detection of diseases is important in order to increase survival rates. Regular monitoring of vital signs is necessary for the early detection of health issues. Due to the high cost, inadequacy, and complexity of monitoring devices, it is challenging for individuals to check their vital signs at home. Consequently, a cost-effective, broadly accessible, and easy-to-use system is necessary for health monitoring. For this purpose, we developed a portable and wireless acquisition electronic device to help patients record physiologically relevant signals such as ECG, EMG, EEG, and EOG for continuous monitoring. The key components of the acquisition system are a portable device, a Wi-Fi router, a SQL server, and a graphical user interface (GUI). In this study, a cost-effective, fairly low-power Internet-of-Things (IoT)-based health monitoring system was built employing a portable device incorporating analog front ends (AFE) and the ESP 32 Wroom-32. Continuous remote monitoring and diagnostics are made possible by including IoT in the architecture. In the proposed monitoring system, the lightweight Message Queue Telemetry Transport (MQTT) protocol was used. A GUI is constructed that shows near-real-time data in a web browser and can be accessed from any operating system. The accuracy of the acquired signals was validated by comparing the individual’s ECG recorded in a remote device through the IoT cloud with a conventional biomedical certified ECG machine. The AFEs were built and evaluated based on the amplitude and bandwidth of ECG, EMG, EEG, and EOG signals. The cost and power analysis, as well as other key parameters are presented. Compared to similar existing boards, our developed system demonstrates high configurable sampling frequency, high Common Mode Rejection Ratio (CMRR) and high transmission throughput with no packet loss while costing significantly less and consuming moderate power. This makes the proposed system suited for the acquisition of multichannel physiological signals for home applications.

在医疗保健领域,早期发现疾病对于提高存活率非常重要。定期监测生命体征对于及早发现健康问题十分必要。由于监测设备价格昂贵、不完善和复杂,个人在家中检查生命体征具有挑战性。因此,有必要开发一种成本效益高、可广泛使用且易于操作的健康监测系统。为此,我们开发了一种便携式无线采集电子设备,帮助患者记录心电图、肌电图、脑电图和眼电图等生理相关信号,进行连续监测。采集系统的关键部件包括便携式设备、Wi-Fi 路由器、SQL 服务器和图形用户界面 (GUI)。在这项研究中,我们利用一个包含模拟前端(AFE)和 ESP 32 Wroom-32 的便携式设备,构建了一个基于物联网(IoT)的高性价比、低功耗健康监测系统。通过将物联网纳入该架构,实现了持续的远程监控和诊断。在拟议的监测系统中,使用了轻量级消息队列遥测传输(MQTT)协议。构建的图形用户界面可在网络浏览器中显示近乎实时的数据,并可从任何操作系统进行访问。通过物联网云将远程设备记录的个人心电图与传统的生物医学认证心电图机进行比较,验证了所获取信号的准确性。根据心电图、肌电图、脑电图和眼电图信号的振幅和带宽,建立并评估了 AFE。报告还介绍了成本和功耗分析以及其他关键参数。与现有的类似电路板相比,我们开发的系统具有可配置的高采样频率、高共模抑制比(CMRR)和无数据包丢失的高传输吞吐量,同时成本显著降低,功耗适中。因此,我们提出的系统非常适合家庭应用中多通道生理信号的采集。
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引用次数: 0
Aspects of conceptualization, development, and simulation of an extracellular vesicles' bulk isolation device for cosmetic and therapeutic applications 用于美容和治疗的细胞外囊泡批量分离装置的构思、开发和模拟方面
Pub Date : 2024-05-12 DOI: 10.1016/j.bea.2024.100125
Franck M Senda, Gilles C Roy

This paper discusses the concept and model to develop a prototype extracellular vesicle bulk-isolation device (EBID). It proposes an engineering design and potential ways to mitigate limitations in the currently available extracellular vesicle (EV) isolation techniques. A more convenient isolation technique is developed and presented to ensure production-scale isolation and purification of the specific size of EV (approximately 0.1 to 0.34 µm) from a large quantity of cell-culture media or biological fluid sources. A more appropriate design concept was established based on the chitosan-assisted precipitation of EV techniques and the membrane filtration technology-based prototype. After that, a novel theoretical model for bulk isolation of EVs was developed and presented using pressure-driven circulation and particulate flow in the EBID loop, where the EV production results from the biofluid flowing through the EBID membrane filter module (MFM). Governing equations are coupled with Darcy's law to investigate the biofluid flow behavior in the EBID MFM, therefore simulating the isolation process of EVs from their biofluids. The flow characteristics of the EV isolation process within the EBID MFM are theoretically simulated and discussed for improved isolation yield with a high degree of quality and purity.

本文讨论了开发细胞外囊泡批量分离装置(EBID)原型的概念和模型。它提出了一种工程设计和潜在方法,以缓解目前可用的细胞外囊泡 (EV) 分离技术的局限性。该研究开发并介绍了一种更方便的分离技术,可确保从大量细胞培养介质或生物液体源中分离和纯化特定大小的 EV(约 0.1 至 0.34 µm),并实现规模化生产。在壳聚糖辅助沉淀 EV 技术和基于膜过滤技术的原型基础上,建立了更合适的设计理念。随后,利用 EBID 循环中的压力驱动循环和微粒流,开发并提出了一种用于批量分离 EV 的新型理论模型,其中 EV 的产生源于流经 EBID 膜过滤组件(MFM)的生物流体。为了研究生物流体在 EBID MFM 中的流动行为,我们采用了达西定律耦合控制方程,从而模拟了将 EV 从其生物流体中分离出来的过程。理论上模拟并讨论了 EBID MFM 中 EV 分离过程的流动特性,以提高分离产量和纯度。
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引用次数: 0
Investigating the impact of contact pressure on photoplethysmograms 研究接触压力对光敏血流图的影响
Pub Date : 2024-04-15 DOI: 10.1016/j.bea.2024.100123
Jukka-Pekka Sirkiä, Tuukka Panula, Matti Kaisti

Photoplethysmography (PPG) sensors are widely used to measure a variety of physiological parameters, from heart rate to clinically important peripheral oxygen saturation (SpO2). The ease of obtaining a PPG signal simply by placing the sensor on a body site with even remotely sufficient vasculature (typically the wrist, finger, earlobe, or temple) can easily lead to overlooking the aspect of appropriate sensor contact pressure (Pc). We sought to investigate the effects of Pc from the perspective of: (i) SpO2, (ii) pulse arrival time (PAT), and (iii) PPG features. Consequently, we developed a finger cuff device to measure multispectral (green, red, and infrared (IR)) PPG signals at different Pc levels. The SpO2 values were found to increase, driven by the IR component, above the theoretical maximum of 100% slightly after the level of the mean arterial pressure. The maximum variation due to Pc was approximately 1.9 percentage points. PAT values calculated using the waveform feet of the red and IR channels were the most robust. PPG features were also sensitive to varying sensor Pc levels, with each feature showing a rather unique response. However, in general, a Pc between 20–30 mmHg (a slight Pc) and the level of diastolic blood pressure is likely to produce the best results on the features. Overall, the results showed that sensor Pc is a source of inaccuracy in PPG analysis and therefore should be given more consideration in device designs.

光电血氧饱和度 (PPG) 传感器被广泛用于测量各种生理参数,从心率到临床上重要的外周血氧饱和度 (SpO2)。只需将传感器放置在有足够血管的身体部位(通常是手腕、手指、耳垂或太阳穴),就能轻松获得 PPG 信号,这很容易导致忽略适当的传感器接触压力 (Pc)。我们试图从以下角度研究 Pc 的影响:(i) SpO2、(ii) 脉搏到达时间 (PAT) 和 (iii) PPG 特征。因此,我们开发了一种指套设备,用于测量多光谱(绿色、红色和红外 (IR)不同 Pc 水平下的 PPG 信号。结果发现,在红外分量的驱动下,SpO2 值在平均动脉压水平略高于 100%的理论最大值后上升。Pc 导致的最大变化约为 1.9 个百分点。使用红色和红外通道波形脚计算的 PAT 值最为稳健。PPG 特征对传感器 Pc 水平的变化也很敏感,每个特征都显示出相当独特的响应。不过,一般来说,Pc 值介于 20-30 mmHg(轻微 Pc 值)和舒张压水平之间,可能会产生最佳的特征结果。总之,研究结果表明,传感器 Pc 是 PPG 分析不准确的一个原因,因此在设备设计中应给予更多的考虑。
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引用次数: 0
Advancements in nanoengineered paclitaxel formulations: A comprehensive review of blood-brain barrier infiltration strategies for glioblastoma therapy 纳米工程紫杉醇制剂的进展:胶质母细胞瘤治疗的血脑屏障渗透策略综述
Pub Date : 2024-04-09 DOI: 10.1016/j.bea.2024.100122
Stabak Das , Prithviraj Chakraborty , Debarupa Dutta Chakraborty , Lila Kanta Nath

Glioblastoma multiform (GBM), the most occurring brain tumor comprises radiation therapy, chemotherapy, and surgery as its treatment modalities. A significant hurdle is the insufficient or impeded transport of drugs to the central nervous system (CNS), linked to the protective influence of the blood-brain barrier (BBB). Nanotechnology can help to deliver therapeutic drugs into the central nervous system (CNS) by crossing the BBB. Paclitaxel (PTX) is a broad-spectrum anticancer compound that possesses scientifically proven anticancer activity. Despite having limited applications due to partial solubility and toxicity due to cosolvent preparation, it has shown encouraging outcomes in the treatment of GBM. In these cases, nanotechnology and nanoparticles added certain advantages such as increasing drug half-life, lowering toxicity, and enhancing the permeability and retention across BBB in tumor targeting. This review article is aimed at summarizing the current state of research works on nanotechnology and nanoparticles (NPs) containing PTX in the treatment of Glioblastoma.

多形性胶质母细胞瘤(GBM)是发病率最高的脑肿瘤,其治疗方法包括放疗、化疗和手术。一个重要的障碍是药物向中枢神经系统(CNS)的传输不足或受阻,这与血脑屏障(BBB)的保护作用有关。纳米技术可以帮助穿过血脑屏障将治疗药物输送到中枢神经系统(CNS)。紫杉醇(PTX)是一种广谱抗癌化合物,具有科学证明的抗癌活性。尽管由于共溶剂制备造成的部分溶解性和毒性而导致其应用有限,但它在治疗 GBM 方面取得了令人鼓舞的成果。在这些情况下,纳米技术和纳米颗粒增加了一些优势,如增加药物半衰期、降低毒性、提高肿瘤靶向药物在 BBB 中的渗透性和滞留性。这篇综述文章旨在总结含有 PTX 的纳米技术和纳米颗粒(NPs)在治疗胶质母细胞瘤方面的研究现状。
{"title":"Advancements in nanoengineered paclitaxel formulations: A comprehensive review of blood-brain barrier infiltration strategies for glioblastoma therapy","authors":"Stabak Das ,&nbsp;Prithviraj Chakraborty ,&nbsp;Debarupa Dutta Chakraborty ,&nbsp;Lila Kanta Nath","doi":"10.1016/j.bea.2024.100122","DOIUrl":"https://doi.org/10.1016/j.bea.2024.100122","url":null,"abstract":"<div><p>Glioblastoma multiform (GBM), the most occurring brain tumor comprises radiation therapy, chemotherapy, and surgery as its treatment modalities. A significant hurdle is the insufficient or impeded transport of drugs to the central nervous system (CNS), linked to the protective influence of the blood-brain barrier (BBB). Nanotechnology can help to deliver therapeutic drugs into the central nervous system (CNS) by crossing the BBB. Paclitaxel (PTX) is a broad-spectrum anticancer compound that possesses scientifically proven anticancer activity. Despite having limited applications due to partial solubility and toxicity due to cosolvent preparation, it has shown encouraging outcomes in the treatment of GBM. In these cases, nanotechnology and nanoparticles added certain advantages such as increasing drug half-life, lowering toxicity, and enhancing the permeability and retention across BBB in tumor targeting. This review article is aimed at summarizing the current state of research works on nanotechnology and nanoparticles (NPs) containing PTX in the treatment of Glioblastoma.</p></div>","PeriodicalId":72384,"journal":{"name":"Biomedical engineering advances","volume":"7 ","pages":"Article 100122"},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667099224000112/pdfft?md5=814c8467bd5ceca6ef71177d92eef918&pid=1-s2.0-S2667099224000112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140631379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immobilization of novel synthesized phosphobetaine zwitterions on polyethersulphone (PES) hemodialysis membranes to induce hemocompatibility: Experimental, molecular docking, and ex-vivo inflammatory biomarker investigations 在聚醚砜(PES)血液透析膜上固定新型合成的磷脂酰亚胺齐聚物以诱导血液相容性:实验、分子对接和体内外炎症生物标志物研究
Pub Date : 2024-03-29 DOI: 10.1016/j.bea.2024.100120
Ubong Eduok , Shaghayegh Saadati , Victoria Doan , Ahmed Shoker , Amira Abdelrasoul

Hemodialysis therapy is a crucial life-saving treatment for severe kidney conditions, particularly in cases where organ transplantation is limited. However, the use of polymeric membranes in clinical dialyzers can trigger undesirable reactions in the blood, such as complement, leukocyte, and coagulation activations. These reactions can lead to hypertension, cardiovascular diseases, and even death, due to compatibility issues. This paper presents a study on the development and application of a novel phosphobetaine zwitterion, immobilized on polyethersulphone (PES) clinical hemodialysis membranes, to improve hemocompatibility. The study also introduces a new method for immobilizing a zwitterionic PVP-phosphobetaine polymer on a PES membrane, using a polydopamine (PDA) crosslinker. The synthesized membranes were characterized, and their performance in terms of blood-protein adsorption and subsequent interaction, specifically with fibrinogen, was investigated to evaluate hemocompatibility. The selection of the phosphobetaine polymer was driven by its capacity to form an electrically neutral zwitterionic hydration layer, which serves as a protective barrier, preventing fibrinogen adsorption. Without this zwitterionic polymer, blood proteins interact with the bare membrane, initiating biological processes that lead to inflammation when exposed to uremic blood. Molecular docking studies were conducted to understand the interactions between various ligands and specific serum protein components. The phosphate and carbonyl chemical groups on the pyrrolidinone zwitterionic moiety were found to form polar interactions with specific amino acids. Exvivo investigations involving incubated coated membranes and uremic blood samples from end-stage renal disease (ESRD) patients revealed that they caused weaker complement and coagulation activation compared to bare PES membranes. In addition, the inflammatory biomarkers have been studied to shed light on their potential impact on patients' quality of life. This study contributes to our understanding of the implications of blood-protein fouling and the hemocompatibility challenges faced by blood-contacting devices used in hemodialysis for ESRD patients, who are prone to membrane-related health complications.

血液透析疗法是治疗严重肾病的重要救命疗法,尤其是在器官移植受限的情况下。然而,在临床透析器中使用聚合物膜会引发血液中的不良反应,如补体、白细胞和凝血活化。由于兼容性问题,这些反应可能导致高血压、心血管疾病,甚至死亡。本文介绍了一种固定在聚醚砜(PES)临床血液透析膜上的新型磷脂酰亚胺齐聚物的开发和应用研究,以改善血液相容性。研究还介绍了一种使用聚多巴胺(PDA)交联剂在聚醚砜膜上固定聚乙烯吡咯烷酮-膦基甜菜碱聚合物的新方法。对合成的膜进行了表征,并研究了它们在血液蛋白吸附和随后的相互作用(特别是与纤维蛋白原的相互作用)方面的性能,以评估其血液相容性。之所以选择磷脂酰基聚合物,是因为它能形成电中性的齐聚物水合层,起到保护屏障的作用,防止纤维蛋白原吸附。如果没有这种齐聚物聚合物,血液蛋白就会与裸膜相互作用,启动生物过程,从而在接触尿毒症血液时导致炎症。为了了解各种配体与特定血清蛋白成分之间的相互作用,我们进行了分子对接研究。研究发现,吡咯烷酮齐聚物上的磷酸和羰基化学基团与特定氨基酸形成极性相互作用。对涂膜和终末期肾病(ESRD)患者尿毒症血样进行的体外研究表明,与裸露的 PES 膜相比,涂膜对补体和凝血的激活作用较弱。此外,还对炎症生物标志物进行了研究,以了解它们对患者生活质量的潜在影响。这项研究有助于我们了解血液蛋白污垢的影响,以及用于 ESRD 患者血液透析的血液接触设备所面临的血液兼容性挑战,因为 ESRD 患者很容易出现与膜相关的健康并发症。
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引用次数: 0
Determining Diagnostic Utility of EEG for Assessing Stroke Severity using Deep Learning Models 利用深度学习模型确定脑电图对评估中风严重程度的诊断效用
Pub Date : 2024-03-29 DOI: 10.1016/j.bea.2024.100121
Shatakshi Singh , Dimple Dawar , Esha Mehmood , Jeyaraj Durai Pandian , Rajeshwar Sahonta , Subhash Singla , Amit Batra , Cheruvu Siva Kumar , Manjunatha Mahadevappa

Stroke has become a leading cause of disability worldwide. Early medication and rehabilitation is the key to help post-stroke survivors recover faster. Presently, doctors rely on imaging modalities like CT/MRI for diagnosing stroke patients. The diagnosis done using these modalities can be highly subjective. Apart from this, these imaging modalities are very costly, time taking and inconvenient for the patients. So there is a need of faster, portable and an automated diagnostic system for assessing post-stroke conditions so that right measures can be taken in the right time. To cater to this need EEG comes in handy because of its portable nature. So, in this work, utility of EEG has been studied to diagnose three aspects of stroke: 1) type of stoke, 2) affected artery and 3) severity of stroke. To achieve this, one-minute resting state EEG data was used to extract 57 features. The features were ranked and selected using ranking algorithm and deep learning (DL) models were trained with supervision from information extracted using MRI data. To find out type of stroke and affected artery DWI, SWI and MRA images were used, and severity of stroke was recorded in terms of NIHSS score. Three different DL models were trained for each task i.e. type of stroke, affected artery and severity of stroke. For classifying type of stroke an accuracy of 97.74% was obtained using 37 features. For stroke severity, the model gave RMSE of 2.1955 with a high correlation value (r = 0.91). The DL model for classifying affected artery used 33 features and gave accuracy of 95.7%. It was also found that less complex time domain features and QEEG features were frequently selected out of 57 features for all the DL models. Features in delta and theta sub-bands were frequently selected along with QEEG features. The work presented here established that EEG can act as a reliable modality for faster diagnosis of stroke specifics and hence can help medical professionals in speeding the decision making process.

中风已成为全球致残的主要原因。早期药物治疗和康复是帮助中风后幸存者更快康复的关键。目前,医生依靠 CT/MRI 等成像模式来诊断中风患者。使用这些方法进行诊断可能非常主观。除此之外,这些成像模式还非常昂贵,耗时长,给患者带来不便。因此,需要更快速、便携和自动化的诊断系统来评估中风后的状况,以便在正确的时间采取正确的措施。为了满足这一需求,脑电图因其便携性而派上了用场。因此,在这项工作中,研究了脑电图在诊断中风三个方面的作用:1)中风类型;2)受影响动脉;3)中风严重程度。为此,我们使用一分钟静息状态脑电图数据提取了 57 个特征。使用排序算法对这些特征进行排序和选择,并在监督下根据磁共振成像数据提取的信息训练深度学习(DL)模型。为了找出中风类型和受影响的动脉,使用了 DWI、SWI 和 MRA 图像,并根据 NIHSS 评分记录了中风的严重程度。针对每项任务,即中风类型、受影响动脉和中风严重程度,训练了三种不同的 DL 模型。使用 37 个特征对中风类型进行分类的准确率为 97.74%。对于中风严重程度,模型的均方根误差为 2.1955,相关值很高(r = 0.91)。用于受影响动脉分类的 DL 模型使用了 33 个特征,准确率为 95.7%。研究还发现,在所有 DL 模型的 57 个特征中,较不复杂的时域特征和 QEEG 特征经常被选中。德尔塔和θ子带特征以及 QEEG 特征经常被选中。本文介绍的工作证明,脑电图可以作为一种可靠的模式,用于更快地诊断中风的具体情况,从而帮助医疗专业人员加快决策过程。
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Biomedical engineering advances
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