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The Application of Three-Dimensional-Printed Hydrogels in Bone Tissue Engineering. 三维打印水凝胶在骨组织工程中的应用。
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-10-01 Epub Date: 2024-01-17 DOI: 10.1089/ten.TEB.2023.0218
Chengcheng Zhang, Tengbin Shi, Dingwei Wu, Dingxiang Hu, Wenwen Li, Jie Fei, Wenge Liu

Bone defects are a prevalent clinical issue that presents a serious medical challenge. Bone tissue engineering (BTE) has emerged as an effective approach for treating large bone defects. Hydrogels, as hydrophilic three-dimensional polymers, are recognized as suitable material for BTE due to their excellent biocompatibility and degradability. However, the submicron and nanoporous structure of hydrogels limits the survival of osteoblasts, hindering bone tissue regeneration. In recent years, 3D printing technology has attracted appreciable attention. The use of hydrogels as 3D-printed ink facilitates the printing of hydrogels in any desired shape, enabling personalized or more complex requirements. This article provides a systematic review of the latest applications of 3D-printed hydrogels in BTE. These hydrogels serve as a multifunctional platform for the next generation technology in treating bone defects. The advantages and limitations of 3D-printed hydrogels in BTE are discussed, and future research directions are explored. This review can form the basis for future hydrogel design.

骨缺损是一个普遍存在的临床问题,也是一项严峻的医学挑战。骨组织工程(BTE)已成为治疗大面积骨缺损的有效方法。水凝胶作为亲水性三维聚合物,具有良好的生物相容性和可降解性,是公认的适用于 BTE 的材料。然而,水凝胶的亚微米和纳米多孔结构限制了成骨细胞的存活,阻碍了骨组织的再生。近年来,三维打印技术备受关注。使用水凝胶作为三维打印墨水,可以打印出任何所需形状的水凝胶,从而满足个性化或更复杂的要求。本文系统回顾了三维打印水凝胶在 BTE 中的最新应用。这些水凝胶是治疗骨缺损的下一代技术的多功能平台。文章讨论了三维打印水凝胶在 BTE 中的优势和局限性,并探讨了未来的研究方向。本综述可作为未来水凝胶设计的基础。
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引用次数: 0
The Structure, Biology, and Mechanical Function of Tendon/Ligament-Bone Interfaces. 肌腱/韧带-骨界面的结构、生物学和机械功能。
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-10-01 Epub Date: 2024-03-05 DOI: 10.1089/ten.TEB.2023.0295
Huizhi Wang, Kaixin He, Cheng-Kung Cheng

After tendon or ligament reconstruction, the interface between the hard bone and soft connective tissue is considerably weakened and is difficult to restore through healing. The tendon/ligament-bone interface is mechanically the weakest point under tensile loading and is often the source of various postoperative complications, such as bone resorption and graft laxity. A comprehensive understanding of the macro- and microfeatures of the native tendon/ligament-bone interface would be beneficial for developing strategies for regenerating the tissue. This article discusses the structural, biological, and mechanical features of the tendon/ligament-bone interfaces and how these can be affected by aging and loading conditions.

肌腱或韧带重建后,硬骨和软结缔组织之间的界面会大大减弱,很难通过愈合恢复。肌腱/韧带-骨界面在拉伸载荷作用下是力学上最薄弱的部位,通常是各种术后并发症(如骨吸收和移植物松弛)的根源。全面了解原生肌腱/韧带-骨界面的宏观和微观特征有利于制定组织再生策略。本文讨论了肌腱/韧带-骨界面的结构、生物和机械特征,以及这些特征如何受到老化和负载条件的影响。影响声明 本综述对肌腱/韧带-骨界面的结构、生物和机械特征以及这些特征如何受到老化和负载条件的影响进行了最新总结。对这些特征的透彻了解为开发韧带/肌腱重建和软硬组织界面工程的先进技术奠定了重要基础。
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引用次数: 0
The Pathological Factors Involved in Current In Vitro Atherosclerotic Models. 当前体外动脉粥样硬化模型中的病理因素
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-10-01 Epub Date: 2024-03-01 DOI: 10.1089/ten.TEB.2023.0272
Yuxin Bao, Hangyu Zhang, Danbo Wang, Peishi Yan, Shuai Shao, Zhengyao Zhang, Bo Liu, Na Li

Cardiovascular disease stemmed from atherosclerosis (AS) is well recognized to be the predominant cause of global death. To comprehensively clarify the pathogenesis of AS, exploit effective drugs, as well as develop therapeutic solutions, various atherosclerotic models were constructed in vitro and widely utilized by the scientific community. Compared with animal models, the in vitro atherosclerotic models play a prominent role not only in the targeted research of single pathological factor related to AS in the human derived system, but also in the combined study on multipathological factors leading to AS, thereby contributing tremendously to the in-depth elucidation of atherosclerotic pathological process. In the current review, a variety of pathological factors incorporated into the existing atherosclerotic models in vitro are broadly elaborated, including the pathological mechanism, in vitro simulation approaches, and the desired improvement perspectives for reproducing each pathological factor. In addition, this review also summarizes the advantages and disadvantages of current atherosclerotic models as well as their potential functionality. Finally, the promising aspects for future atherosclerotic models in vitro with potential advances are also discussed.

动脉粥样硬化引发的心血管疾病已被公认为全球死亡的主要原因。为了全面阐明动脉粥样硬化的发病机理,开发有效药物,制定治疗方案,人们在体外构建了各种动脉粥样硬化模型,并被科学界广泛利用。与动物模型相比,体外动脉粥样硬化模型不仅在有针对性地研究人体衍生系统中与动脉粥样硬化相关的单一病理因素方面,而且在导致动脉粥样硬化的多种病理因素的联合研究方面发挥着突出的作用,从而为深入阐明动脉粥样硬化的病理过程做出了巨大贡献。本综述广泛阐述了现有动脉粥样硬化体外模型中加入的各种病理因素,包括病理机制、体外模拟方法以及再现每种病理因素所需的改进前景。此外,本综述还总结了当前动脉粥样硬化模型的优缺点及其潜在功能。最后,还讨论了未来动脉粥样硬化体外模型的前景和潜在进展。
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引用次数: 0
Trends in Injectable Biomaterials for Vocal Fold Regeneration and Long-Term Augmentation. 用于声带褶皱再生和长期增厚的注射生物材料的发展趋势。
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-23 DOI: 10.1089/ten.TEB.2024.0134
Mika Brown, Hideaki Okuyama, Masaru Yamashita, Maryam Tabrizian, Nicole Y K Li-Jessen

Human vocal folds (VFs), a pair of small, soft tissues in the larynx, have a layered mucosal structure with unique mechanical strength to support high-level tissue deformation by phonation. Severe pathological changes to VF have causes including surgery, trauma, age-related atrophy, and radiation, and lead to partial or complete communication loss and difficulty in breathing and swallowing. VF glottal insufficiency requires injectable VF biomaterials such as hyaluronan, calcium hydroxyapatite, and autologous fat to augment VF functions. Although these biomaterials provide an effective short-term solution, significant variations in patient response and requirements of repeat reinjection remain notable challenges in clinical practice. Tissue engineering strategies have been actively explored in the search of an injectable biomaterial that possesses the capacity to match native tissue's material properties while promoting permanent tissue regeneration. This review aims to assess the current status of biomaterial development in VF tissue engineering. The focus will be on examining state-of-the-art techniques including modification with bioactive molecules, cell encapsulation, composite materials, and in situ crosslinking with click chemistry. We will discuss potential opportunities that can further leverage these engineering techniques in the advancement of VF injectable biomaterials. Impact Statement Injectable vocal fold (VF) biomaterials augment tissue function through minimally invasive procedures, yet there remains a need for long-term VF reparation. This article reviews cutting-edge research in VF biomaterial development to propose safe and effective tissue engineering strategies for improving regenerative outcomes. Special focus is paid to methods to enhance bioactivity and achieve tissue-mimicking mechanical properties, longer in situ stability, and inherent biomaterial bioactivity.

人类声带(VF)是喉部的一对细小软组织,具有分层粘膜结构,具有独特的机械强度,可通过发音支持高水平的组织变形。VF发生严重病变的原因包括手术、外伤、老年性萎缩和辐射,并导致部分或完全丧失交流能力以及呼吸和吞咽困难。VF 声门功能不全需要注射 VF 生物材料(如透明质酸、羟基磷灰石钙和自体脂肪)来增强 VF 功能。虽然这些生物材料提供了有效的短期解决方案,但患者反应的显著差异和重复再注射的要求仍然是临床实践中的显著挑战。为了寻找一种既能与原生组织的材料特性相匹配,又能促进组织永久再生的可注射生物材料,人们一直在积极探索组织工程策略。本综述旨在评估 VF 组织工程中生物材料的开发现状。重点将放在研究最先进的技术上,包括生物活性分子修饰、细胞封装、复合材料以及利用点击化学进行原位交联。我们还将讨论进一步利用这些工程技术促进可注射 VF 生物材料发展的潜在机会。
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引用次数: 0
Advancing Cartilage Tissue Engineering: A Review of 3D Bioprinting Approaches and Bioink Properties. 推进软骨组织工程:三维生物打印方法和生物墨水特性综述。
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-23 DOI: 10.1089/ten.TEB.2024.0168
Gabriele Boretti, Arsalan Amirfallah, Kyle J Edmunds, Helena Hamzehpour, Olafur E Sigurjonsson

Articular cartilage is crucial in human physiology, and its degeneration poses a significant public health challenge. While recent advancements in 3D bioprinting and tissue engineering show promise for cartilage regeneration, there remains a gap between research findings and clinical application. This review critically examines the mechanical and biological properties of hyaline cartilage, along with current 3D manufacturing methods and analysis techniques. Moreover, we provide a quantitative synthesis of bioink properties used in cartilage tissue engineering. After screening 181 initial works, 33 studies using extrusion bioprinting were analyzed and synthesized, presenting results that indicate the main materials, cells, and methods utilized for mechanical and biological evaluation. Altogether, this review motivates the standardization of mechanical analyses and biomaterial assessments of 3D bioprinted constructs to clarify their chondrogenic potential.

关节软骨对人体生理至关重要,其退化对公共卫生构成了重大挑战。虽然三维生物打印和组织工程学的最新进展显示了软骨再生的前景,但研究成果与临床应用之间仍存在差距。本综述批判性地研究了透明软骨的机械和生物特性,以及当前的三维制造方法和分析技术。此外,我们还对软骨组织工程中使用的生物墨水特性进行了定量综述。在对 181 项初步研究进行筛选后,我们对 33 项使用挤压生物打印技术的研究进行了分析和综合,结果表明了机械和生物评估所使用的主要材料、细胞和方法。总之,这篇综述推动了三维生物打印构建物的机械分析和生物材料评估的标准化,以明确其软骨生成潜力。
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引用次数: 0
Emerging diabetes therapies: Regenerating pancreatic β cells. 新兴糖尿病疗法:再生胰腺β细胞。
IF 6.4 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-14 DOI: 10.1089/ten.teb.2024.0041
Haojie Zhang,Yaxin Wei,Yubo Wang,Jialin Liang,Yifan Hou,Xiaobo Nie,Junqing Hou
The incidence of diabetes mellitus (DM) is steadily increasing annually, with 537 million diabetic patients as of 2021. Restoring diminished β cell mass or impaired islet function is crucial in treating DM, particularly type 1 diabetes mellitus (T1DM). However, the regenerative capacity of islet β cells, which primarily produce insulin, is severely limited, and natural regeneration is only observed in young rodents or children. Hence, there is an urgent need to develop advanced therapeutic approaches that can regenerate endogenous β cells or replace them with stem cell (SC)-derived or engineered β-like cells. Current strategies for treating insulin-dependent DM mainly include promoting the self-replication of endogenous β cells, inducing SC differentiation, reprogramming non-β cells into β-like cells, and generating pancreatic-like organoids through cell-based intervention. In this Review, we discuss the current state of the art in these approaches, describe associated challenges, propose potential solutions, and highlight ongoing efforts to optimize β cell or islet transplantation and related clinical trials. These effective cell-based therapies will generate a sustainable source of functional β cells for transplantation and lay strong foundations for future curative treatments for DM.
糖尿病(DM)的发病率每年都在稳步上升,到 2021 年将有 5.37 亿糖尿病患者。恢复减少的β细胞质量或受损的胰岛功能对于治疗糖尿病,尤其是1型糖尿病(T1DM)至关重要。然而,主要产生胰岛素的胰岛β细胞的再生能力非常有限,只有在年轻的啮齿类动物或儿童身上才能观察到自然再生。因此,亟需开发先进的治疗方法,使内源性β细胞再生,或用干细胞(SC)衍生或改造的β样细胞替代内源性β细胞。目前治疗胰岛素依赖型糖尿病的策略主要包括促进内源性β细胞的自我复制、诱导SC分化、将非β细胞重编程为β样细胞,以及通过细胞干预生成胰腺样器官组织。在本综述中,我们将讨论这些方法的技术现状,描述相关的挑战,提出潜在的解决方案,并重点介绍目前为优化β细胞或胰岛移植及相关临床试验所做的努力。这些有效的细胞疗法将为移植提供可持续的功能性β细胞来源,并为未来治疗糖尿病奠定坚实的基础。
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引用次数: 0
In-Stent Re-Endothelialization Strategies: Cells, Extracellular Matrix, and Extracellular Vesicles. 支架内再内皮化策略:细胞、ECM 和细胞外囊泡。
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-12 DOI: 10.1089/ten.TEB.2024.0178
Min-Kyu Kang, Seon-Hee Heo, Jeong-Kee Yoon

Arterial stenosis caused by atherosclerosis often requires stent implantation to increase the patency of target artery. However, such external devices often lead to in-stent restenosis due to inadequate re-endothelialization and subsequent inflammatory responses. Therefore, re-endothelialization strategies after stent implantation have been developed to enhance endothelial cell recruitment or to capture circulating endothelial progenitor cells. Notably, recent research indicates that coating stent surfaces with biogenic materials enhances the long-term safety of implantation, markedly diminishing the risk of in-stent restenosis. In this review, we begin by describing the pathophysiology of coronary artery disease and in-stent restenosis. Then, we review the characteristics and materials of existing stents used in clinical practice. Lastly, we explore biogenic materials aimed at accelerating re-endothelialization, including extracellular matrix, cells, and extracellular vesicles. This review helps overcome the limitations of current stents for cardiovascular disease and outlines the next phase of research and development.

动脉粥样硬化导致的动脉狭窄通常需要植入支架来增加目标动脉的通畅性。然而,由于再内皮化不足和随后的炎症反应,这种外部装置往往会导致支架内再狭窄。因此,人们开发了支架植入后的再内皮化策略,以增强内皮细胞招募或捕获循环内皮祖细胞。值得注意的是,最近的研究表明,在支架表面涂覆生物材料可提高植入的长期安全性,显著降低支架内再狭窄的风险。在本综述中,我们首先介绍冠状动脉疾病和支架内再狭窄的病理生理学。然后,我们回顾了临床实践中使用的现有支架的特性和材料。最后,我们探讨了旨在加速再内皮化的生物材料,包括细胞外基质、细胞和细胞外囊泡。这篇综述将有助于克服目前支架在治疗心血管疾病方面的局限性,并勾勒出下一阶段的研发方向。
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引用次数: 0
Surgical Therapy and Tissue Engineering for Meniscal Repair. 半月板修复的手术疗法和组织工程学。
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-08-21 DOI: 10.1089/ten.TEB.2024.0060
Hao Wang, Jie Wu, Liupu Yang, Shuyun Liu, Xiang Sui, Quanyi Guo, Mingxue Chen

Meniscal damage is one of the prevalent causes of knee pain, swelling, instability, and functional compromise, frequently culminating in osteoarthritis (OA). Timely and appropriate interventions are crucial to relieve symptoms and prevent or delay the onset of OA. Contemporary surgical treatments include total or partial meniscectomy, meniscal repair, allograft meniscal transplantation, and synthetic meniscal implants, but each presents its specific limitations. Recently, regenerative medicine and tissue engineering have emerged as promising fields, offering innovative prospects for meniscal regeneration and repair. This review delineates current surgical methods, elucidating their specific indications, advantages, and disadvantages. Concurrently, it delves into state-of-the-art tissue engineering techniques aimed at the functional regenerative repair of meniscus. Recommendations for future research and clinical practice are also provided.

半月板损伤是导致膝关节疼痛、肿胀、不稳定和功能受损的主要原因之一,常常最终导致骨关节炎(OA)。及时采取适当的干预措施对于缓解症状、预防或延缓 OA 的发生至关重要。当代外科治疗方法包括半月板全部或部分切除术、半月板修复术、同种异体半月板移植术和合成半月板植入物,但每种方法都有其特定的局限性。最近,再生医学和组织工程成为前景广阔的领域,为半月板再生和修复提供了创新前景。本综述介绍了目前的手术方法,阐明了这些方法的具体适应症、优点和缺点。同时,它还深入探讨了旨在实现半月板功能性再生修复的最新组织工程技术。此外,还对未来的研究和临床实践提出了建议。
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引用次数: 0
An Exploration of the Role of Osteoclast Lineage Cells in Bone Tissue Engineering. 探讨破骨细胞系细胞在骨组织工程中的作用。
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-08-19 DOI: 10.1089/ten.TEB.2024.0126
Eoin J Devoy, Erfan Jabari, George Kotsanos, Robert H Choe, John P Fisher

Bone defects because of age, trauma, and surgery, which are exacerbated by medication side effects and common diseases such as osteoporosis, diabetes, and rheumatoid arthritis, are a problem of epidemic scale. The present clinical standard for treating these defects includes autografts and allografts. Although both treatments can promote robust regenerative outcomes, they fail to strike a desirable balance of availability, side effect profile, consistent regenerative efficacy, and affordability. This difficulty has contributed to the rise of bone tissue engineering (BTE) as a potential avenue through which enhanced bone regeneration could be delivered. BTE is founded upon a paradigm of using biomaterials, bioactive factors, osteoblast lineage cells (ObLCs), and vascularization to cue deficient bone tissue into a state of regeneration. Despite promising preclinical results, BTE has had modest success in being translated into the clinical setting. One barrier has been the simplicity of its paradigm relative to the complexity of biological bone. Therefore, this paradigm must be critically examined and expanded to better account for this complexity. One potential avenue for this is a more detailed consideration of osteoclast lineage cells (OcLCs). Although these cells ostensibly oppose ObLCs and bone regeneration through their resorptive functions, a myriad of investigations have shed light on their potential to influence bone equilibrium in more complex ways through their interactions with both ObLCs and bone matrix. Most BTE research has not systematically evaluated their influence. Yet contrary to expectations associated with the paradigm, a selection of BTE investigations has demonstrated that this influence can enhance bone regeneration in certain contexts. In addition, much work has elucidated the role of many controllable scaffold parameters in both inhibiting and stimulating the activity of OcLCs in parallel to bone regeneration. Therefore, this review aims to detail and explore the implications of OcLCs in BTE and how they can be leveraged to improve upon the existing BTE paradigm.

由于年龄、外伤和手术造成的骨缺损,以及药物副作用和骨质疏松症、糖尿病、类风湿性关节炎等常见疾病,使骨质缺损问题更加严重。目前治疗这些缺陷的临床标准包括自体移植和异体移植。虽然这两种治疗方法都能促进强大的再生效果,但它们未能在可用性、副作用、稳定的再生疗效和可负担性之间取得理想的平衡。这一难题促使骨组织工程(BTE)的兴起,成为增强骨再生的潜在途径。骨组织工程的基础是使用生物材料、生物活性因子、成骨细胞系细胞(ObLCs)和血管化技术,引导缺损骨组织进入再生状态。尽管临床前研究结果令人鼓舞,但 BTE 在临床应用方面却成效一般。其中一个障碍就是相对于生物骨的复杂性而言,其范例过于简单。因此,必须对这种模式进行严格审查和扩展,以更好地考虑这种复杂性。这方面的一个潜在途径是对破骨细胞系细胞(OcLCs)进行更详细的研究。虽然这些细胞表面上通过其吸收功能反对破骨细胞和骨再生,但无数的研究已经揭示了它们通过与破骨细胞和骨基质相互作用,以更复杂的方式影响骨平衡的潜力。大多数 BTE 研究都没有系统地评估它们的影响。然而,与人们对这一范例的期望相反,一些 BTE 研究表明,在某些情况下,这种影响可以促进骨再生。此外,许多研究还阐明了许多可控支架参数在抑制和刺激 OcLCs 活性以及骨再生方面的作用。因此,本综述旨在详细介绍和探讨 OcLCs 在 BTE 中的意义,以及如何利用它们来改进现有的 BTE 范例。
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引用次数: 0
Magnetic Cell Targeting for Cardiovascular Tissue Engineering. 用于心血管组织工程的磁性细胞靶向。
IF 5.1 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-08-19 DOI: 10.1089/ten.TEB.2024.0103
Akankshya Shradhanjali, Jayne T Wolfe, Brandon J Tefft

There is a critical need for novel approaches to translate cell therapy and regenerative medicine to clinical practice. Magnetic cell targeting with site specificity has started to open avenues in these fields as a potential therapeutic platform. Magnetic targeting is gaining popularity in the field of biomedicine due to its ability to concentrate and retain at a target site while minimizing deleterious effects at off-target sites. It is regarded as a relatively straightforward and safe approach for a wide range of therapeutic applications. This review discusses the latest advancements and approaches in magnetic cell targeting using endocytosed and surface-bound magnetic nanoparticles as well as in vivo tracking using magnetic resonance imaging (MRI). The most common form of magnetic nanoparticles is superparamagnetic iron oxide nanoparticles (SPION). The biodegradable and biocompatible properties of these magnetically responsive particles and capacity for rapid endocytosis into cells make them a breakthrough in targeted therapy. This review further discusses specific applications of magnetic targeting approaches in cardiovascular tissue engineering including myocardial regeneration, therapeutic angiogenesis, and endothelialization of implantable cardiovascular devices.

将细胞疗法和再生医学转化为临床实践亟需新方法。作为一种潜在的治疗平台,具有靶点特异性的磁性细胞靶向技术已开始在这些领域开辟道路。磁性靶向技术在生物医学领域越来越受欢迎,因为它能够集中并保留在靶点,同时最大限度地减少对非靶点的有害影响。在广泛的治疗应用中,它被认为是一种相对直接和安全的方法。本综述将讨论利用内吞和抗体结合的磁性纳米粒子进行磁性细胞靶向以及利用核磁共振成像进行体内跟踪的最新进展和方法。最常见的磁性粒子形式是超顺磁性氧化铁纳米粒子(SPION)。这些磁响应粒子具有生物可降解性和生物相容性,并能快速内吞进入细胞,这使它们在靶向治疗方面取得了突破性进展。本综述进一步讨论了磁性靶向方法的具体应用,包括心肌再生、植入式心血管设备的内皮化和其他再生医学应用。
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引用次数: 0
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