Bioengineering

生物工程
  • 文章类型: Journal Article
    骨质疏松症是由骨吸收和骨形成之间的不平衡引起的全身性骨骼疾病。目前的治疗主要涉及全身药物和激素治疗。然而,这些系统治疗缺乏方向性,对局部严重的骨质疏松症通常无效。具有复杂不良反应的可能性。因此,使用生物活性材料或外部干预的治疗策略已成为最有前途的方法.这篇综述提出了12个骨质疏松症相关病理变化的微环境治疗目标,包括炎症因子和活性氧(ROS)的局部积累,线粒体动力学失衡,胰岛素抵抗,破坏骨细胞自噬,骨细胞凋亡失衡,神经分泌物的变化,骨细胞的老化,增加局部骨组织血管破坏,减少再生。此外,本文综述了基于这些微环境治疗目标的有效或潜在的生物物理和生化刺激的研究现状,并总结了不同生物工程刺激的优势和最佳参数,以支持骨质疏松症治疗和骨再生的临床前和临床研究。最后,该综述解决了当前的挑战和未来的研究前景。
    Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.
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  • 文章类型: Journal Article
    从牙锥束计算机断层扫描(CBCT)精确分割牙源性囊性病变(OCL)对于有效的牙科诊断至关重要。尽管监督学习方法在分割各种疾病方面已经显示出实际的诊断结果,它们分割涵盖不同亚类品种的OCL的能力尚未得到广泛研究。
    在这项研究中,我们提出了一种新的监督学习方法,称为OCL-Net,它结合了多尺度U-Net模型,以及经过联合监督损失训练的自动适应机制。回顾性收集了一家医院的匿名CBCT图像。为了评估我们的模型提高颌面外科医生诊断效率的能力,我们进行了一项诊断评估,包括7名临床医生在有或没有自动分段面罩辅助的情况下进行诊断.
    我们收集了300张匿名CBCT图像,这些图像被手动注释以用于分割掩模。大量实验证明了我们的OCL-Net对CBCTOCL分割的有效性,实现88.84%的整体骰子得分,IoU得分为81.23%,AUC评分为92.37%。通过我们的诊断评估,我们发现,当临床医生得到来自OCL-Net的分割标签的辅助时,他们的平均诊断准确率从53.21%提高到55.71%,而平均花费时间从101s显著减少到47s(P<0.05)。
    这些发现证明了我们的方法作为CBCT图像中OCL的鲁棒自动分割系统的潜力,而分段面罩可用于进一步提高OCLs牙科诊断效率。
    UNASSIGNED: Precise segmentation of Odontogenic Cystic Lesions (OCLs) from dental Cone-Beam Computed Tomography (CBCT) is critical for effective dental diagnosis. Although supervised learning methods have shown practical diagnostic results in segmenting various diseases, their ability to segment OCLs covering different sub-class varieties has not been extensively investigated.
    UNASSIGNED: In this study, we propose a new supervised learning method termed OCL-Net that combines a Multi-Scaled U-Net model, along with an Auto-Adapting mechanism trained with a combined supervised loss. Anonymous CBCT images were collected retrospectively from one hospital. To assess the ability of our model to improve the diagnostic efficiency of maxillofacial surgeons, we conducted a diagnostic assessment where 7 clinicians were included to perform the diagnostic process with and without the assistance of auto-segmentation masks.
    UNASSIGNED: We collected 300 anonymous CBCT images which were manually annotated for segmentation masks. Extensive experiments demonstrate the effectiveness of our OCL-Net for CBCT OCLs segmentation, achieving an overall Dice score of 88.84%, an IoU score of 81.23%, and an AUC score of 92.37%. Through our diagnostic assessment, we found that when clinicians were assisted with segmentation labels from OCL-Net, their average diagnostic accuracy increased from 53.21% to 55.71%, while the average time spent significantly decreased from 101s to 47s (P<0.05).
    UNASSIGNED: The findings demonstrate the potential of our approach as a robust auto-segmentation system on OCLs in CBCT images, while the segmented masks can be used to further improve OCLs dental diagnostic efficiency.
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  • 文章类型: Journal Article
    考虑到生物技术专业传统的制造过程学习方法中存在的问题,本文介绍了“重组人红细胞生成制造过程虚拟仿真实验”课程的开发和实施过程。该实验结合了现代生物制造技术和三维信息技术,以重组人红细胞生成药物为焦点。本文阐述了教学理念,目标,内容,实施方法,实验程序,互动的步骤,和实验中使用的评估标准。通过创新性实验方案设计,教学方法,和评估系统,本课程旨在培养学生在生物制药工程领域的分析和解决问题的能力,同时也拓宽了学生的视野和视野。
    Considering the issues present in traditional learning methods of manufacturing process for biotechnology majors, this paper presents the development and implementation process of the course entitled \"Virtual Simulation Experiment of Recombinant Human Erythropoiesis Manufacturing Process\". The experiment combines modern biological manufacturing technology and three-dimensional information technology, with recombinant human erythropoiesis drug serving as the focal point. This paper elaborates on the teaching concepts, objectives, contents, implementation methods, experimental procedures, interactive steps, and assessment criteria used in the experiment. Through innovative experimental scheme design, teaching methodologies, and evaluation systems, this course aims to cultivate students\' analytical and problem-solving skills in the field of biopharmaceutical engineering, while also broadening students\' perspective and expanding their vision.
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  • 文章类型: Journal Article
    稀土元素的特殊性质有效地拓宽了其应用领域。如何准确识别和有效分离具有相似半径和化学性质的目标稀土离子仍然是一个巨大的挑战。这里,我们使用石墨烯氧化(GO)层之间的工程大肠杆菌膜构建了精确的二维(2D)异质通道。异质通道中Lanmodulin(LanM)与稀土离子之间的结合能力和相应构象变化的差异允许精确识别和筛分scan离子(Sc3)。工程大肠杆菌膜不仅可以保护LanM的结构和功能的完整性,丰富的脂质和糖,还通过相互作用帮助大肠杆菌膜紧密贴在GO纳米片上,防止膨胀和控制层间间距精确到亚纳米。显然,2D异质通道对三价离子表现出优异的选择性(SFFe3+/Sc3+≈3),特别是对于稀土元素中的Sc3离子具有高选择性(SFCe/Sc≈167,SFLa/Sc≈103)。长期稳定性和拉伸应变测试验证了膜的出色稳定性。因此,这个简单的,高效,和具有成本效益的工作提供了一个建议,为构建二维夹层异质通道进行精确筛分,并为Sc的高效提取提出了有价值的策略。本文受版权保护。保留所有权利。
    The special properties of rare earth elements (REE) have effectively broadened their application fields. How to accurately recognize and efficiently separate target rare earth ions with similar radii and chemical properties remains a formidable challenge. Here, precise two-dimensional (2D) heterogeneous channels are constructed using engineered E. coli membranes between graphene oxide (GO) layers. The difference in binding ability and corresponding conformational change between Lanmodulin (LanM) and rare earth ions in the heterogeneous channel allows for precisely recognizing and sieving of scandium ions (Sc3+). The engineered E. coli membranes not only can protect the integrity of structure and functionality of LanM, the rich lipids and sugars, but also help the Escherichia coli (E. coli) membranes closely tile on the GO nanosheets through interaction, preventing swelling and controlling interlayer spacing accurately down to the sub-nanometer. Apparently, the 2D heterogeneous channels showcase excellent selectivity for trivalent ions (SFFe /Sc≈3), especially for Sc3+ ions in REE with high selectivity (SFCe/Sc≈167, SFLa/Sc≈103). The long-term stability and tensile strain tests verify the membrane\'s outstanding stability. Thus, this simple, efficient, and cost-effective work provides a suggestion for constructing 2D interlayer heterogeneous channels for precise sieving, and this valuable strategy is proposed for the efficient extraction of Sc.
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  • 文章类型: Journal Article
    胸主动脉瘤(TAA)是一种威胁生命的血管疾病,通常与潜在的遗传原因有关。对人类TAA发病机制的理解不足突出了对更好的疾病模型的需求。这里,我们通过结合人诱导多能干细胞(hiPSCs)在动物宿主中建立了功能性人TAA模型,生物工程血管移植物(BVGs),基因编辑我们从等基因对照hiPSC衍生的血管平滑肌细胞(SMC)和突变SMC基因编辑以携带Loeys-Dietz综合征(LDS)相关致病变体(TGFBR1A230T)产生了BVG。我们还使用来自患有LDS的患者的细胞(PatientA230T/+)和使用遗传校正的细胞(患者+/+)产生了hiPSC衍生的BVG。然后将对照和实验性BVG植入裸鼠的颈总动脉中。TGFBR1A230T变体导致BVG的机械性能受损,导致较低的爆裂压力和缝线保留强度。携带变体的BVGs随时间在体内扩张,类似于人类TAA的形成。空间转录组学分析显示,与患者+/+BVG相比,PatientA230T/+BVG中的细胞外基质(ECM)形成基因表达缺陷。组织学分析和蛋白质分析验证了PatientA230T/BVGs和患者组织中的定量和定性ECM缺陷,包括降低胶原羟基化。血管收缩测试证实,PatientA230T/BVG中的SMC组织也受损。用小干扰RNA沉默胶原修饰酶减少SMC来源的组织构建体中的胶原脯氨酸羟基化。这些研究证明了BVG在动物宿主中模拟人TAA形成的实用性,并强调了降低的胶原蛋白修饰酶活性在人TAA形成中的作用。
    Thoracic aortic aneurysm (TAA) is a life-threatening vascular disease frequently associated with underlying genetic causes. An inadequate understanding of human TAA pathogenesis highlights the need for better disease models. Here, we established a functional human TAA model in an animal host by combining human induced pluripotent stem cells (hiPSCs), bioengineered vascular grafts (BVGs), and gene editing. We generated BVGs from isogenic control hiPSC-derived vascular smooth muscle cells (SMCs) and mutant SMCs gene-edited to carry a Loeys-Dietz syndrome (LDS)-associated pathogenic variant (TGFBR1A230T). We also generated hiPSC-derived BVGs using cells from a patient with LDS (PatientA230T/+) and using genetically corrected cells (Patient+/+). Control and experimental BVGs were then implanted into the common carotid arteries of nude rats. The TGFBR1A230T variant led to impaired mechanical properties of BVGs, resulting in lower burst pressure and suture retention strength. BVGs carrying the variant dilated over time in vivo, resembling human TAA formation. Spatial transcriptomics profiling revealed defective expression of extracellular matrix (ECM) formation genes in PatientA230T/+ BVGs compared with Patient+/+ BVGs. Histological analysis and protein assays validated quantitative and qualitative ECM defects in PatientA230T/+ BVGs and patient tissue, including decreased collagen hydroxylation. SMC organization was also impaired in PatientA230T/+ BVGs as confirmed by vascular contraction testing. Silencing of collagen-modifying enzymes with small interfering RNAs reduced collagen proline hydroxylation in SMC-derived tissue constructs. These studies demonstrated the utility of BVGs to model human TAA formation in an animal host and highlighted the role of reduced collagen modifying enzyme activity in human TAA formation.
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  • 文章类型: Journal Article
    磁性机器人具有在人体难以到达的空腔中导航的先天能力,使它们成为微创诊断和治疗疾病的有前途的工具。尽管取得了重大进展,在恶劣的生理条件下开发具有理想运动能力和完全生物相容性的机器人仍然具有挑战性,这对磁性机器人的设计和材料合成提出了新的要求。与用无机材料合成的机器人相比,像细胞这样的天然生物,细菌或其他微藻表现出理想的体内应用特性,如生物相容性,可变形性,自动荧光,和自我推进,以及易于进行功能治疗工程。在这个过程中,这些生物可以在生物流体或外部磁场中提供自主推进,同时通过集成人工机器人来保留它们的功能,从而帮助靶向治疗递送。这种机器人被称为生物混合磁机器人,在这个小型审查中,最近的进展,包括他们的设计,工程和治疗递送的潜力将被讨论。此外,将介绍历史背景和突出的例子,和复杂性,潜在的陷阱,将讨论与生物混合磁性机器人技术相关的机会。
    Magnetic robots possess an innate ability to navigate through hard-to-reach cavities in the human body, making them promising tools for diagnosing and treating diseases minimally invasively. Despite significant advances, the development of robots with desirable locomotion and full biocompatibility under harsh physiological conditions remains challenging, which put forward new requirements for magnetic robots\' design and material synthesis. Compared to robots that are synthesized with inorganic materials, natural organisms like cells, bacteria or other microalgae exhibit ideal properties for in vivo applications, such as biocompatibility, deformability, auto-fluorescence, and self-propulsion, as well as easy for functional therapeutics engineering. In the process, these organisms can provide autonomous propulsion in biological fluids or external magnetic fields, while retaining their functionalities with integrating artificial robots, thus aiding targeted therapeutic delivery. This kind of robotics is named bio-hybrid magnetic robotics, and in this mini-review, recent progress including their design, engineering and potential for therapeutics delivery will be discussed. Additionally, the historical context and prominent examples will be introduced, and the complexities, potential pitfalls, and opportunities associated with bio-hybrid magnetic robotics will be discussed.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    应用生物工程技术在口腔环境中实现骨再生是一个日益突出的领域。然而,合成材料的临床使用存在一定的风险。浓缩生长因子(LPCGF)的液相,作为一种生物衍生材料,具有优越的生物相容性。在这项研究中,LPCGF被用作组织工程支架,托管牙囊细胞(DFCs)以促进骨再生。体内和体外实验结果表明,该平台显着增强了DFCs中成骨标志物的表达,如碱性磷酸酶(ALP),runt相关转录因子2(Runx2),和I型胶原蛋白(Col1a1)。同时,它减少了炎症相关基因的表达,特别是白细胞介素-6(IL-6)和白细胞介素-8(IL-8),从而减轻炎症微环境对DFCs的负面影响。对潜在机制的进一步研究表明,该过程随时间受到WNT途径的调节。我们的研究结果表明,LPCGF,凭借其良好的物理特性,作为脚手架拥有巨大的潜力。它可以有效地携带DFCs,从而为骨骼再生提供最佳的初始环境。此外,LPCGF努力紧密地模拟创伤后骨愈合的机制以促进骨形成。这为骨再生工程提供了新的视角和见解。
    The application of bioengineering techniques for achieving bone regeneration in the oral environment is an increasingly prominent field. However, the clinical use of synthetic materials carries certain risks. The liquid phase of concentrated growth factor (LPCGF), as a biologically derived material, exhibits superior biocompatibility. In this study, LPCGF was employed as a tissue engineering scaffold, hosting dental follicle cells (DFCs) to facilitate bone regeneration. Both in vivo and in vitro experimental results demonstrate that this platform significantly enhances the expression of osteogenic markers in DFCs, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and type I collagen (Col1a1). Simultaneously, it reduces the expression of inflammation-related genes, particularly interleukin-6 (IL-6) and interleukin-8 (IL-8), thereby alleviating the negative impact of the inflammatory microenvironment on DFCs. Further investigation into potential mechanisms reveals that this process is regulated over time by the WNT pathway. Our research results demonstrate that LPCGF, with its favorable physical characteristics, holds great potential as a scaffold. It can effectively carry DFCs, thereby providing an optimal initial environment for bone regeneration. Furthermore, LPCGF endeavors to closely mimic the mechanisms of bone healing post-trauma to facilitate bone formation. This offers new perspectives and insights into bone regeneration engineering.
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  • 文章类型: Journal Article
    子宫内膜在卵巢激素动态水平的调节下经历一系列精确的每月变化,其特征是反复脱落和随后的再生而没有疤痕。这提供了子宫内膜损伤期间伤口愈合的潜力。生物工程材料突出了组成型细胞和细胞外基质的忠实复制,在更大程度上模拟了子宫内膜的物理和生物力学特性。在这一领域取得了重大进展,和功能性子宫内膜组织生物工程允许在体外深入研究子宫内膜和子宫肌层缺损的调节因素,并提供了缓解产科和妇科并发症的高度治疗方法。然而,关于将生物工程技术应用于人类子宫内膜的最新进展,还有很多尚待了解。这里,我们总结了子宫内膜再生和提高女性生殖潜能的生物材料和生物工程模型的现有发展。
    The endometrium undergoes a series of precise monthly changes under the regulation of dynamic levels of ovarian hormones that are characterized by repeated shedding and subsequent regeneration without scarring. This provides the potential for wound healing during endometrial injuries. Bioengineering materials highlight the faithful replication of constitutive cells and the extracellular matrix that simulates the physical and biomechanical properties of the endometrium to a larger extent. Significant progress has been made in this field, and functional endometrial tissue bioengineering allows an in-depth investigation of regulatory factors for endometrial and myometrial defects in vitro and provides highly therapeutic methods to alleviate obstetric and gynecological complications. However, much remains to be learned about the latest progress in the application of bioengineering technologies to the human endometrium. Here, we summarize the existing developments in biomaterials and bioengineering models for endometrial regeneration and improving the female reproductive potential.
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  • 文章类型: Journal Article
    通过液-液相分离(LLPS)形成的无膜细胞器(MLO)由于对活细胞中生化和细胞过程的时空控制而得到了广泛的研究。这些发现为生物分子缩合物的形成和功能化的物理化学原理提供了宝贵的见解,这为开发能够解决各种应用场景的通用相分离系统铺平了道路。这里,我们强调了构建具有可编程和功能特性的合成MLO的潜力。值得注意的是,我们组织了这些合成无膜隔室如何被利用来操纵酶活性和代谢反应。这篇综述的目的是激发读者深刻理解合成MLO在调节酶促反应和代谢过程控制中的广泛作用,并鼓励合理设计可控和功能性无膜隔室,用于广泛的生物工程应用。
    Membraneless organelles (MLOs) formed by liquid-liquid phase separation (LLPS) have been extensively studied due to their spatiotemporal control of biochemical and cellular processes in living cells. These findings have provided valuable insights into the physicochemical principles underlying the formation and functionalization of biomolecular condensates, which paves the way for the development of versatile phase-separating systems capable of addressing a variety of application scenarios. Here, we highlight the potential of constructing synthetic MLOs with programmable and functional properties. Notably, we organize how these synthetic membraneless compartments have been capitalized to manipulate enzymatic activities and metabolic reactions. The aim of this review is to inspire readerships to deeply comprehend the widespread roles of synthetic MLOs in the regulation enzymatic reactions and control of metabolic processes, and to encourage the rational design of controllable and functional membraneless compartments for a broad range of bioengineering applications.
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