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ColMA‐based bioprinted 3D scaffold allowed to study tenogenic events in human tendon stem cells 基于 ColMA 的生物打印三维支架可用于研究人类肌腱干细胞的韧化事件
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-31 DOI: 10.1002/btm2.10723
Giacomo Cortella, Erwin Pavel Lamparelli, Maria Camilla Ciardulli, Joseph Lovecchio, Emanuele Giordano, Nicola Maffulli, Giovanna Della Porta
The advent of bioprinting has enabled the creation of precise three‐dimensional (3D) cell cultures suitable for biomimetic in vitro models. In this study, we developed a novel protocol for 3D printing methacrylated collagen (ColMa, or PhotoCol®) combined with tendon stem/progenitor cells (hTSPCs) derived from human tendon explants. Although pure ColMa has not previously been proposed as a printable hydrogel, this paper outlines a robust and highly reproducible pipeline for bioprinting this material. Indeed, we successfully fabricated a 3D bioengineered scaffold and cultured it for 21 days under perfusion conditions with medium supplemented with growth/differentiation factor‐5 (GDF‐5). This bioprinting pipeline and the culture conditions created an exceptionally favorable 3D environment, enabling the cells to proliferate, exhibit tenogenic behaviors, and produce a new collagen type I matrix, thereby remodeling the surrounding environment. Indeed, over the 21‐day culture period under perfusion condition, tenomodulin expression showed a significant upregulation on day 7, with a 2.3‐fold increase, compared to days 14 and 21. Collagen type I gene expression was upregulated nearly 10‐fold by day 14. This trend was further confirmed by western blot analysis, which revealed a statistically significant difference in tenomodulin expression between day 21 and both day 7 and day 14. For type I collagen, significant differences were observed between day 0 and day 21, as well as between day 0 and day 14, with a p‐value of 0.01. These results indicate a progressive over‐expression of type I collagen, reflecting cell differentiation towards a proper tenogenic phenotype. Cytokines, such as IL‐8 and IL‐6, levels peaked at 8566 and 7636 pg/mL, respectively, on day 7, before decreasing to 54 and 46 pg/mL by day 21. Overall, the data suggest that the novel ColMa bioprinting protocol effectively provided a conducive environment for the growth and proper differentiation of hTSPCs, showcasing its potential for studying cell behavior and tenogenic differentiation.
生物打印技术的出现使精确的三维(3D)细胞培养物成为可能,它适用于仿生体外模型。在这项研究中,我们开发了一种新的三维打印方法,将甲基丙烯酸胶原蛋白(ColMa 或 PhotoCol®)与从人体肌腱外植体中提取的肌腱干/祖细胞(hTSPCs)结合在一起。虽然纯 ColMa 以前从未被提议用作可打印的水凝胶,但本文概述了生物打印这种材料的稳健且高度可重现的管道。事实上,我们成功制作了三维生物工程支架,并在灌注条件下用补充了生长/分化因子-5(GDF-5)的培养基培养了 21 天。这种生物打印管道和培养条件创造了一个非常有利的三维环境,使细胞能够增殖,表现出韧性行为,并产生新的 I 型胶原基质,从而重塑周围环境。事实上,在灌注条件下进行的 21 天培养中,腱鞘蛋白的表达在第 7 天显著上调,与第 14 天和第 21 天相比增加了 2.3 倍。到第 14 天,I 型胶原蛋白基因表达上调了近 10 倍。这一趋势在 Western 印迹分析中得到了进一步证实,该分析表明,第 21 天与第 7 天和第 14 天之间的tenomodulin 表达有显著的统计学差异。就 I 型胶原蛋白而言,在第 0 天和第 21 天之间以及第 0 天和第 14 天之间观察到了显著差异,P 值为 0.01。这些结果表明 I 型胶原蛋白逐渐过度表达,反映了细胞向适当的腱鞘表型分化。细胞因子(如 IL-8 和 IL-6)的水平在第 7 天分别达到 8566 和 7636 pg/mL 的峰值,到第 21 天分别降至 54 和 46 pg/mL。总之,这些数据表明,新型 ColMa 生物打印方案有效地为 hTSPCs 的生长和适当分化提供了有利环境,展示了其在研究细胞行为和韧带分化方面的潜力。
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引用次数: 0
Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease 利用可溶解微针贴片在牙龈中轻松部署米诺环素,辅助治疗牙周病
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-21 DOI: 10.1002/btm2.10730
Huimin Li, Xueyu Wen, Xinyi Gong, Yange Wu, Puxuan Zhao, Yun Zhang, Zhuomin Sha, Hao Chang, Xuepeng Chen
Minocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra‐pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline‐loaded dissolvable microneedle (Mino‐DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two‐step casting micro‐molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino‐DMN patch features an array of minocycline‐enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino‐DMN inhibits pro‐inflammatory factors, promotes anti‐inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino‐DMN offers a simple, efficient, user‐friendly strategy for the adjunctive treatment of periodontal disease.
米诺环素是牙周病辅助治疗的常用药物。然而,目前主流的局部用药主要依靠口袋内给药,虽然避免了传统全身用药的副作用,但也带来了不便、不适和需要专业人员协助等挑战,从而影响了患者的依从性。在此,我们介绍一种米诺环素载体可溶微针(Mino-DMN)贴片,它能将米诺环素局部、高效地输送到牙龈,用于治疗牙周炎。该贴片采用真空干燥和冷冻干燥两步铸造微成型工艺,将米诺环素浓缩在微针部分,并限制其向贴片衬底扩散。由此制成的 Mino-DMN 贴片具有富含米诺环素的明胶 MN 阵列和多孔 HA 贴片衬底。微针能以足够的机械强度穿透牙龈,迅速将米诺环素释放到牙龈组织中,确保药物在局部长时间停留,并最大限度地减少药物在唾液中的流失。体内实验表明,Mino-DMN 可抑制促炎因子、促进抗炎因子和刺激骨形成,其效果优于局部用药,也可媲美给药不便和不适的 Periocline®。该研究提出的 Mino-DMN 为牙周病的辅助治疗提供了一种简单、高效、用户友好的策略。
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引用次数: 0
Temperature‐sensitive sodium beta‐glycerophosphate/chitosan hydrogel loaded with all‐trans retinoic acid regulates Pin1 to inhibit the formation of spinal cord injury‐induced rat glial scar 装载全反式维甲酸的温度敏感型β-甘油磷酸钠/壳聚糖水凝胶调节Pin1,抑制脊髓损伤诱导的大鼠神经胶质瘢痕的形成
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-17 DOI: 10.1002/btm2.10729
Rongmou Zhang, Ting Tang, Huafeng Zhuang, Peiwen Wang, Haiming Yu, Hao Xu, Xuedong Yao
Glial scar formation is a major obstacle to nerve regeneration following spinal cord injury (SCI). Pin1 and the PI3K/AKT/CDK2 signaling pathway play crucial roles in neuronal regulation, but research on their involvement in glial scarring remains limited. In this study, we have for the first time observed that Pin1, PI3K, AKT, and CDK2 are upregulated and interact with each other following SCI. Further experiments revealed that Pin1 contributes to the development of glial scars by promoting astrocyte proliferation, inhibiting apoptosis, and activating the PI3K/AKT/CDK2 pathway. Additionally, all‐trans retinoic acid (ATRA), a specific chemical inhibitor of Pin1, effectively suppresses Pin1 expression. However, its clinical application is limited by its short half‐life and susceptibility to inactivation. To address these issues, we have developed a thermosensitive sodium beta‐glycerophosphate (β‐GP)/chitosan (CS) hydrogel loaded with ATRA (β‐GP/CS@ATRA). This hydrogel exhibits favorable morphology and biocompatibility. Compared to free ATRA, the β‐GP/CS@ATRA hydrogel significantly enhances functional motor recovery after SCI and protects spinal cord tissue, thereby inhibiting glial scar formation. Mechanistically, ATRA administration blocks the development of glial scars and the activation of the PI3K/AKT/CDK2 pathway by inhibiting Pin1 expression. This study suggests that combining ATRA with a hydrogel to target Pin1 expression may be a promising strategy for treating glial scar formation following SCI.
神经胶质瘢痕的形成是脊髓损伤(SCI)后神经再生的主要障碍。Pin1和PI3K/AKT/CDK2信号通路在神经元调控中发挥着关键作用,但它们参与胶质瘢痕形成的研究仍然有限。在这项研究中,我们首次观察到在脊髓损伤后,Pin1、PI3K、AKT 和 CDK2 上调并相互影响。进一步的实验发现,Pin1 通过促进星形胶质细胞增殖、抑制细胞凋亡和激活 PI3K/AKT/CDK2 通路来促进胶质疤痕的形成。此外,全反式维甲酸(ATRA)是 Pin1 的一种特异性化学抑制剂,能有效抑制 Pin1 的表达。然而,由于其半衰期短且易失活,其临床应用受到了限制。为了解决这些问题,我们开发了一种负载有 ATRA 的热敏性β-甘油磷酸钠(β-GP)/壳聚糖(CS)水凝胶(β-GP/CS@ATRA)。这种水凝胶具有良好的形态和生物相容性。与游离 ATRA 相比,β-GP/CS@ATRA 水凝胶能显著促进 SCI 后的运动功能恢复,保护脊髓组织,从而抑制神经胶质瘢痕的形成。从机理上讲,ATRA 通过抑制 Pin1 的表达,阻止了神经胶质疤痕的形成和 PI3K/AKT/CDK2 通路的激活。这项研究表明,将 ATRA 与水凝胶结合来靶向 Pin1 的表达可能是治疗 SCI 后神经胶质疤痕形成的一种很有前景的策略。
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引用次数: 0
Recent regulatory developments in EU Medical Device Regulation and their impact on biomaterials translation 欧盟医疗器械法规的最新监管动态及其对生物材料翻译的影响
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-16 DOI: 10.1002/btm2.10721
Klaudia M. Jurczak, Torben A. B. van der Boon, Raul Devia‐Rodriguez, Richte C. L. Schuurmann, Jelmer Sjollema, Lidia van Huizen, Jean‐Paul P. M. De Vries, Patrick van Rijn
We envision this work to assist researchers and medical device developers (beside other stakeholders) to better understand biomaterial‐based medical device development and its approval process proposed by the new MDR and IVDR in the European Union, as more complex biomaterials emerge, with the MDR reflecting the progress in biomaterial discoveries. Additionally, insufficient international harmonization in regulatory laws and poor‐quality data reporting contribute to the problem. This review describes the possible reasons for a slowing biomaterials translational trend observed over the past decades, focusing on the European Market, and suggests a feasible approach for biomaterials‐based medical device translation into the clinic. Suitable solutions to upgrade biomaterial translation to the clinic have not yet been provided by the field: no additional hurdles should be imposed for researchers, clinicians, the medical device industry, and insurance companies, which all should collaborate on bringing innovative solutions to patients. The new MDR and IVDR represent a substantial advancement in ensuring patient safety and reflect a major step forward in healthcare. However, they should not constrain innovation in biomaterials‐based medical device development. Incorporating reverse engineering from patient safety and a ‘safe by design’ (SbD) strategy early into medical device development might lead to a smoother and successful approval process. A solid R&D phase, with an emphasis on device safety and performance assessment, is fundamental to ensure an effective transition into the clinic. We offer an overview of the recently implemented regulations on medical devices and in vitro diagnostics across the EU, describing a shifting paradigm in the field of biomaterials discovery. As more complex biomaterials emerge, suitable regulations will be necessary to keep bringing safe and well‐performing medical solutions to patients.
我们希望这项工作能帮助研究人员和医疗器械开发人员(以及其他利益相关者)更好地理解基于生物材料的医疗器械开发及其审批流程,欧盟新的 MDR 和 IVDR 提出了更复杂的生物材料,MDR 反映了生物材料发现的进展。此外,监管法律的国际协调性不足和数据报告质量不高也是造成这一问题的原因之一。本综述以欧洲市场为重点,描述了过去几十年来生物材料转化趋势放缓的可能原因,并提出了将基于生物材料的医疗器械转化到临床的可行方法。该领域尚未提供将生物材料转化为临床产品的合适解决方案:研究人员、临床医生、医疗器械行业和保险公司不应再设置额外障碍,他们应通力合作,为患者提供创新解决方案。新的 MDR 和 IVDR 标志着在确保患者安全方面取得了重大进展,是医疗保健领域的一大进步。但是,它们不应限制基于生物材料的医疗器械开发创新。在医疗器械开发的早期阶段,从患者安全和 "安全设计"(SbD)战略出发进行逆向工程,可能会使审批过程更加顺利和成功。以器械安全和性能评估为重点的扎实研发阶段是确保器械有效进入临床的基础。我们概述了欧盟近期实施的医疗器械和体外诊断法规,描述了生物材料发现领域的范式转变。随着更复杂的生物材料的出现,有必要制定适当的法规,以便继续为患者提供安全、性能良好的医疗解决方案。
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引用次数: 0
Photobiomodulation improves functional recovery after mild traumatic brain injury 光生物调节改善轻度脑外伤后的功能恢复
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-11 DOI: 10.1002/btm2.10727
Andrew R. Stevens, Mohammed Hadis, Abhinav Thareja, Freya G. Anderson, Michael R. Milward, Valentina Di Pietro, Antonio Belli, William Palin, David J. Davies, Zubair Ahmed
Mild traumatic brain injury (mTBI) is a common consequence of head injury but there are no recognized interventions to promote recovery of the brain. We previously showed that photobiomodulation (PBM) significantly reduced the number of apoptotic cells in adult rat hippocampal organotypic slice cultures. In this study, we first optimized PBM delivery parameters for use in mTBI, conducting cadaveric studies to calibrate 660 and 810 nm lasers for transcutaneous delivery of PBM to the cortical surface. We then used an in vivo weight drop mTBI model in adult rats and delivered daily optimized doses of 660, 810 nm, or combined 660/810 nm PBM. Functional recovery was assessed using novel object recognition (NOR) and beam balance tests, whilst histology and immunohistochemistry were used to assess the mTBI neuropathology. We found that PBM at 810, 660 nm, or 810/660 nm all significantly improved both NOR and beam balance performance, with 810 nm PBM having the greatest effects. Histology demonstrated no overt structural damage in the brain after mTBI, however, immunohistochemistry using brain sections showed significantly reduced activation of both CD11b+ microglia and glial fibrillary acidic protein (GFAP)+ astrocytes at 3 days post‐injury. Significantly reduced cortical localization of the apoptosis marker, cleaved caspase‐3, and modest reductions in extracellular matrix deposition after PBM treatment, limited to choroid plexus and periventricular areas were also observed. Our results demonstrate that 810 nm PBM optimally improved functional outcomes after mTBI, reduced markers associated with apoptosis and astrocyte/microglial activation, and thus may be useful as a potential regenerative therapy.
轻度创伤性脑损伤(mTBI)是头部受伤的常见后果,但目前还没有公认的促进大脑恢复的干预措施。我们以前的研究表明,光生物调控(PBM)能显著减少成年大鼠海马有机切片培养物中凋亡细胞的数量。在这项研究中,我们首先优化了用于 mTBI 的 PBM 输送参数,通过尸体研究校准了 660 和 810 nm 激光,以便经皮将 PBM 输送到大脑皮层表面。然后,我们在成年大鼠体内使用了体重下降 mTBI 模型,并每天输送优化剂量的 660、810 nm 或 660/810 nm 组合 PBM。使用新物体识别(NOR)和横梁平衡测试评估功能恢复情况,同时使用组织学和免疫组织化学方法评估 mTBI 神经病理学。我们发现,波长为 810 纳米、660 纳米或 810/660 纳米的 PBM 都能显著提高 NOR 和横梁平衡能力,其中波长为 810 纳米的 PBM 效果最好。组织学显示,创伤后脑损伤后大脑结构没有明显损伤,但是,使用脑切片进行的免疫组化显示,CD11b+小胶质细胞和胶质纤维酸性蛋白(GFAP)+星形胶质细胞的活化在伤后 3 天明显减少。此外,还观察到凋亡标志物--裂解的 Caspase-3 在大脑皮层的定位明显减少,以及 PBM 治疗后细胞外基质沉积的适度减少,但仅限于脉络丛和脑室周围区域。我们的研究结果表明,810 nm PBM 能以最佳方式改善 mTBI 后的功能预后,减少与细胞凋亡和星形胶质细胞/小胶质细胞活化相关的标记物,因此可作为一种潜在的再生疗法。
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引用次数: 0
The hanging‐heart chip: A portable microfluidic device for high‐throughput generation of contractile embryonic stem cell‐derived cardiac spheroids 悬挂式心脏芯片:用于高通量生成收缩胚胎干细胞衍生心脏球的便携式微流体设备
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-08 DOI: 10.1002/btm2.10726
Pei‐Tzu Lai, Cheng‐Kun He, Chi‐Han Li, Jefunnie Matahum, Chia‐Yu Tang, Chia‐Hsien Hsu
Stem cell‐derived cardiac spheroids are promising models for cardiac research and drug testing. However, generating contracting cardiac spheroids remains challenging because of the laborious experimental procedure. Here, we present a microfluidic hanging‐heart chip (HH‐chip) that uses a microchannel and flow‐driven system to facilitate cell loading and culture medium replacement operations to reduce the laborious manual handling involved in the generation of a large quantity of cardiac spheroids. The effectiveness of the HH‐chip was demonstrated by simultaneously forming 50 mouse embryonic stem cell‐derived embryonic bodies, which sequentially differentiated into 90% beating cardiac spheroids within 15 days of culture on the chip. A comparison of our HH‐chip method with traditional hanging‐drop and low‐attachment plate methods revealed that the HH‐chip could generate higher contracting proportions of cardiac spheroids with higher expression of cardiac markers. Additionally, we verified that the contraction frequencies of the cardiac spheroids generated from the HH‐chip were sensitive to cardiotoxic drugs. Overall, our results suggest that the microfluidic hanging drop chip‐based approach is a high‐throughput and highly efficient method for generating contracting mouse embryonic stem cell‐derived cardiac spheroids for cardiac toxicity and drug testing applications.
干细胞衍生的心脏球体是一种很有前景的心脏研究和药物测试模型。然而,由于实验过程繁琐,生成收缩的心脏球体仍具有挑战性。在这里,我们提出了一种微流控悬挂心脏芯片(HH-chip),它使用微通道和流动驱动系统来促进细胞装载和培养基更换操作,从而减少了生成大量心脏球形体时所需的费力人工操作。通过同时形成 50 个小鼠胚胎干细胞衍生的胚胎体,证明了 HH 芯片的有效性,这些胚胎体在芯片上培养 15 天后依次分化成 90% 的搏动心脏球体。将我们的 HH 芯片方法与传统的悬滴法和低附着力平板法进行比较后发现,HH 芯片能生成更高收缩比例的心脏球体,心脏标志物的表达量也更高。此外,我们还验证了由 HH 芯片生成的心脏球体的收缩频率对心脏毒性药物敏感。总之,我们的研究结果表明,基于微流控悬滴芯片的方法是一种高通量、高效率的方法,可生成收缩的小鼠胚胎干细胞衍生心脏球体,用于心脏毒性和药物测试应用。
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引用次数: 0
Cardiovascular patches applied in congenital cardiac surgery: Current materials and prospects 应用于先天性心脏手术的心血管贴片:现有材料与前景
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-09-30 DOI: 10.1002/btm2.10706
Mingze Sun, Vincent Reed LaSala, Caroline Giuglaris, David Blitzer, Sophia Jackman, Senay Ustunel, Kavya Rajesh, David Kalfa
Congenital Heart Defects (CHDs) are the most common congenital anomalies, affecting between 4 and 75 per 1000 live births. Cardiovascular patches (CVPs) are frequently used as part of the surgical armamentarium to reconstruct cardiovascular structures to correct CHDs in pediatric patients. This review aims to evaluate the history of cardiovascular patches, currently available options, clinical applications, and important features of these patches. Performance and outcomes of different patch materials are assessed to provide reference points for clinicians. The target audience includes clinicians seeking data on clinical performance as they make choices between different patch products, as well as scientists and engineers working to develop patches or synthesize new patch materials.
先天性心脏缺陷(CHD)是最常见的先天性畸形,每 1000 名活产婴儿中就有 4 到 75 例。心血管补片(CVPs)经常被用作外科手术的一部分,用于重建心血管结构以矫正儿童患者的先天性心脏病。本综述旨在评估心血管补片的历史、现有选择、临床应用以及这些补片的重要特征。对不同补片材料的性能和效果进行评估,为临床医生提供参考。目标读者包括在选择不同贴片产品时寻求临床表现数据的临床医生,以及致力于开发贴片或合成新贴片材料的科学家和工程师。
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引用次数: 0
A CRISPR mediated point‐of‐care assay for the detection of mucosal calprotectin in an animal model of ulcerative colitis 在溃疡性结肠炎动物模型中检测粘膜钙粘蛋白的 CRISPR 介导的护理点检测法
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-09-25 DOI: 10.1002/btm2.10725
Selena Chia, Tianruo Guo, Ewa M. Goldys, Sophie C. Payne, Wenlu Duan, Nigel H. Lovell, Mohit N. Shivdasani, Fei Deng
Inflammatory bowel disease (IBD) is a chronic disorder associated with inflammation in the gastrointestinal tract, leading to a range of debilitating symptoms. Fecal calprotectin is an established biomarker for ulcerative colitis (UC), one of the main IBD diseases, which provides indications of the presence and severity of inflammation in the digestive tract. Enzyme‐Linked Immunosorbent Assay (ELISA) as a gold standard approach for fecal calprotectin detection is time‐consuming and impractical in point‐of‐care settings. Moreover, obtaining fecal samples from patients is challenging and inhibits longitudinal monitoring. To address these specific problems, we have developed a novel approach for detecting calprotectin which leverages clustered regularly interspaced short palindromic repeats (CRISPR)/Cas technology. We successfully developed a portable tube‐based CRISPR/Cas assay for point‐of‐care testing of calprotectin. This assay showed a detection range from 1 to 10,000 ng/ml (over 4 log units), using both fluorescent and colorimetric analytical techniques. The established assay was further validated through measurements in mucosal samples obtained in an anesthetised preclinical rodent model of UC, with 2–3 times higher calprotectin concentration detected in UC rat samples compared to that of healthy control animals. This point‐of‐care test may provide a rapid, precise, and user‐friendly approach for the diagnosis and monitoring of IBD through mucosal sample testing.
炎症性肠病(IBD)是一种与胃肠道炎症有关的慢性疾病,会导致一系列使人衰弱的症状。粪便钙粘蛋白是溃疡性结肠炎(UC)(主要的 IBD 疾病之一)的一种公认生物标记物,可显示消化道炎症的存在和严重程度。酶联免疫吸附试验(ELISA)是检测粪便钙粘蛋白的金标准方法,但这种方法耗时较长,在护理点环境中并不实用。此外,从患者体内获取粪便样本也具有挑战性,不利于进行纵向监测。为了解决这些具体问题,我们开发了一种新型方法来检测钙黏蛋白,该方法利用了聚类规则间隔短回文重复序列(CRISPR)/Cas 技术。我们成功开发了一种基于 CRISPR/Cas 的便携式试管检测法,用于对犊牛蛋白进行床旁检测。利用荧光和比色分析技术,该检测方法的检测范围为 1 至 10,000 纳克/毫升(超过 4 个对数单位)。通过对麻醉的临床前啮齿动物 UC 模型粘膜样本进行测量,进一步验证了所建立的检测方法,在 UC 大鼠样本中检测到的钙粘蛋白浓度是健康对照动物的 2-3 倍。这种床旁检测法可为通过粘膜样本检测诊断和监测肠道疾病提供一种快速、精确和用户友好的方法。
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引用次数: 0
A novel cytoprotective organ perfusion platform for reconstructing homeostasis of DCD liver while alleviating IRI injury 一种新型细胞保护器官灌注平台,用于重建 DCD 肝脏的稳态,同时减轻 IRI 损伤
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-09-23 DOI: 10.1002/btm2.10724
Tingting Lan, Mingxing Yu, Tao Ming, Hong Wang, Juan Deng, Shuhan Cheng, Zhongyang Shen, Deling Kong
Pump is a vital component for expelling the perfusate in small animal isolated organ normothermic machine perfusion (NMP) systems whose flexible structure and rhythmic contraction play a crucial role in maintaining perfusion system homeostasis. However, the continuous extrusion forming with the rigid stationary shaft of the peristaltic pumps can damage cells, leading to metabolic disorders and eventual dysfunction of transplanted organs. Here, we developed a novel biomimetic blood‐gas system (BBGs) for preventing cell damage. This system mimics the cardiac cycle and features an adjustable inspiratory‐to‐expiratory (IE) ratio to mitigate acidosis caused by continuous oxygen inhalation. In our study, adipose stem cells (ADSCs) were cultured within the circulatory system for 10 min, 2, and 4 h. Compared to the peristaltic pump, the BBGs significantly reduced cell apoptosis and morphological injury while enhancing cell proliferation and adhesion. Additionally, when the supernatant from ADSCs was introduced to LPS‐induced macrophages for 24 h, the BBGs group demonstrated a more pronounced anti‐inflammatory effect, characterized by reduced M1 macrophage expression. Besides, with isolated rat livers from donation after circulatory death (DCD) perfusion with ADSCs for 6 h by the BBGs, we detected fewer apoptotic cells and a reduced inflammatory response, evidenced by down‐regulated TNF‐α expression. The development of BBGs demonstrates the feasibility of recreating physiological liquid–gas circulation in vitro, offering an alternative platform for isolated organ perfusion, especially for applications involving cell therapy.
泵是小动物离体器官常温机器灌注(NMP)系统中排出灌注液的重要部件,其灵活的结构和有节奏的收缩对维持灌注系统的平衡起着至关重要的作用。然而,蠕动泵刚性固定轴形成的连续挤压会损伤细胞,导致代谢紊乱,最终导致移植器官功能障碍。在此,我们开发了一种新型仿生血气系统(BBGs)来防止细胞损伤。该系统模仿心动周期,具有可调节的吸气-呼气(IE)比率,以减轻持续吸入氧气造成的酸中毒。在我们的研究中,脂肪干细胞(ADSCs)在循环系统中分别培养了10分钟、2小时和4小时。与蠕动泵相比,BBGs显著减少了细胞凋亡和形态损伤,同时增强了细胞增殖和粘附。此外,将 ADSCs 的上清液引入 LPS 诱导的巨噬细胞 24 小时后,BBGs 组的抗炎效果更明显,其特征是减少了 M1 巨噬细胞的表达。此外,在循环死亡(DCD)后捐献的大鼠离体肝脏中,用BBGs灌注ADSCs 6小时后,我们发现凋亡细胞减少,炎症反应减弱,TNF-α表达下调就是证明。BBG的开发证明了在体外再造生理液-气循环的可行性,为离体器官灌注提供了一个替代平台,特别是在涉及细胞治疗的应用中。
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引用次数: 0
Macrophages overexpressing interleukin‐10 target and prevent atherosclerosis: Regression of plaque formation and reduction in necrotic core 过量表达白细胞介素-10的巨噬细胞能靶向预防动脉粥样硬化:斑块形成的消退和坏死核心的减少
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-09-17 DOI: 10.1002/btm2.10717
Mingyi Wang, Shanshan Zhou, Yingyun Hu, Wei Tong, Hao Zhou, Mingrui Ma, Xingxuan Cai, Zhengbin Zhang, Luo Zhang, Yundai Chen
Atherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte‐derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)‐10 is widely acknowledged for its anti‐inflammatory effects, systemic administration of IL‐10 has limitations due to its short half‐life and significant systemic side effects. In this study, we aimed to investigate the effectiveness of an approach designed to overexpress IL‐10 in macrophages and subsequently introduce these genetically modified cells into ApoE−/− mice to promote atherosclerosis regression. We engineered RAW264.7 cells to overexpress IL‐10 (referred to as IL‐10M) using lentivirus vectors. The IL‐10M exhibited robust IL‐10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL‐10M can selectively target plaques in ApoE−/− mice and has the potential to reduce plaque area and necrotic core at both early and late stages of plaque progression. Moreover, there was a significant reduction in MMP9, a biomarker associated with plaque rupture, in IL‐10M‐treated plaques from both the early and late intervention groups. Additionally, the administration of IL‐10M showed no obvious side effects. This study serves as proof that cell therapy based on anti‐inflammatory macrophages might be a promising strategy for the intervention of atherosclerosis.
动脉粥样硬化是一种进展缓慢的炎症性疾病,其特点是存在源自单核细胞的巨噬细胞。针对动脉粥样硬化炎症特征的干预措施具有广阔的前景。虽然白细胞介素(IL)-10的抗炎作用已得到广泛认可,但由于其半衰期短且具有明显的全身副作用,因此全身给药具有局限性。在本研究中,我们的目的是研究在巨噬细胞中过表达 IL-10,并随后将这些转基因细胞导入载脂蛋白E-/-小鼠体内以促进动脉粥样硬化消退的方法的有效性。我们利用慢病毒载体改造了 RAW264.7 细胞,使其过表达 IL-10(简称 IL-10M)。IL-10M表现出强劲的IL-10分泌,维持吞噬功能,改善线粒体膜电位,减少超氧化物的产生,并在受到炎症刺激时表现出M2表型倾向。IL-10M可选择性地靶向载脂蛋白E-/-小鼠的斑块,并有可能在斑块进展的早期和晚期减少斑块面积和坏死核心。此外,在早期和晚期干预组中,经IL-10M处理的斑块中与斑块破裂相关的生物标志物MMP9均有明显减少。此外,服用IL-10M无明显副作用。这项研究证明,基于抗炎巨噬细胞的细胞疗法可能是一种很有前景的动脉粥样硬化干预策略。
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Bioengineering & Translational Medicine
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