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Chapter 5. Shear Thinning Hydrogel-based 3D Tissue Modelling 第五章。基于剪切变薄水凝胶的三维组织建模
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00094
Christopher D. Lindsay, S. Heilshorn
Hydrogels are water-swollen, crosslinked polymer networks that can be widely tuned to fit many applications. Hydrogels have been used as tissue engineering platforms for decades, but have not been widely adopted as inks for 3D bioprinting. Compared to the more common liquid solution phase (sol-phase) bioinks, hydrogel (gel-phase) bioinks have many advantages, which will be discussed in Section 1. Section 2 will describe how gel-phase inks can be tuned to include important bioactive cues for specific tissue engineering applications. In Section 3, different crosslinking strategies and materials will be presented for the creation of gel-phase bioinks. Finally, Section 4 will discuss how gel-phase bioinks can be used to create complex structures that are required for the future of advanced medicine.
水凝胶是水膨胀的交联聚合物网络,可以广泛调整以适应许多应用。几十年来,水凝胶一直被用作组织工程平台,但尚未被广泛用作3D生物打印的墨水。与更常见的液相(溶胶相)生物墨水相比,水凝胶(凝胶相)生物墨水具有许多优点,这些将在第1节中讨论。第2节将描述如何凝胶相墨水可以调整,包括重要的生物活性线索,为特定的组织工程应用。在第3节中,将介绍不同的交联策略和材料,以创建凝胶相生物墨水。最后,第4节将讨论如何使用凝胶相生物墨水来创建先进医学未来所需的复杂结构。
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引用次数: 0
Chapter 9. 3D Tissue Modelling of Skeletal Muscle Tissue 第9章。骨骼肌组织的三维组织建模
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00184
M. Costantini, Stefano Testa, Chiara Rinoldi, Nehar Celikkin, J. Idaszek, C. Colosi, A. Barbetta, C. Gargioli, W. Świȩszkowski
Skeletal muscle tissue exhibits an endogenous ability to regenerate. However, the self-repair mechanism is restricted only to minor damage. The increasing number of extensive injuries of skeletal muscles due to various accidents, a more active life-style or cancer resection, combined with the shortcomings of conventional treatment procedures, creates a demand for new, more advanced solutions. Muscle tissue engineering (TE) appears a promising strategy for the fabrication of tissue substitutes from biomaterials, cells and bioactive factors, alone or combined. In this chapter, we present current state of the art of regeneration and engineering of skeletal muscle tissue. The chapter begins with a brief introduction to the structure and functions of skeletal muscle tissue, followed by discussion of cells with potential for repair of muscle injuries and dysfunctions. Next, we provide an overview of natural and synthetic biomaterials used in skeletal muscle TE, as well as description of techniques used to process the biomaterials into scaffolds. We also highlight the importance of mechanical and electrical stimulation during in vitro culture and their effect on cell differentiation and maturation. Last but not least, the latest results of in vivo studies are reported. The chapter is concluded with a short summary and outlook on future developments.
骨骼肌组织表现出一种内源性的再生能力。然而,自我修复机制仅限于轻微损伤。由于各种事故,更积极的生活方式或癌症切除,以及传统治疗方法的缺点,导致越来越多的骨骼肌大面积损伤,这就产生了对新的,更先进的解决方案的需求。肌肉组织工程(TE)是利用生物材料、细胞和生物活性因子单独或联合制造组织替代品的一种很有前途的策略。在本章中,我们介绍了骨骼肌组织再生和工程技术的现状。本章首先简要介绍了骨骼肌组织的结构和功能,然后讨论了具有修复肌肉损伤和功能障碍潜力的细胞。接下来,我们概述了用于骨骼肌TE的天然和合成生物材料,以及用于将生物材料加工成支架的技术描述。我们还强调了体外培养过程中机械和电刺激的重要性及其对细胞分化和成熟的影响。最后但并非最不重要的是,报告了体内研究的最新结果。本章以简短的总结和对未来发展的展望结束。
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引用次数: 2
Chapter 7. Decellularized Tissue Matrix-based 3D Tissue Modeling 第七章。基于脱细胞组织矩阵的三维组织建模
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00148
Sanskrita Das, Ge Gao, Jae Yeon Lee, Jinah Jang, Cho Dong-Woo
The extracellular matrix (ECM), which is ubiquitously present in tissues and organs, is an intricate network composed of multi-domain macromolecules, such as proteins, proteoglycans, and glycoproteins. These molecules assemble in varied proportions, structures, and orientations in different tissues, providing unique biochemical cues and biophysical signals to regulate tissue-specific cellular behaviors. Decellularized ECM (dECM) refers to a category of biomaterials acquired from natural tissues subjected to a combination of decellularization treatments that preserve ECM components and inherent structures eliminating cellular substances. dECM has been considered as one of the most promising biomaterials for recreating functional 3D tissue models because of its superior capacity to comprehensively mimic the original tissue microenvironment. In this chapter, we introduce the structural and functional role of natural ECMs and summarize the representative decellularization and evaluation methods. We also focus on recent applications of dECM in tissue engineering using traditional approaches (e.g., implantable sheets and injectable hydrogels) and 3D cell printing technology.
细胞外基质(extracellular matrix, ECM)广泛存在于组织和器官中,是由蛋白质、蛋白聚糖和糖蛋白等多结构域大分子组成的复杂网络。这些分子在不同的组织中以不同的比例、结构和方向聚集,为调节组织特异性细胞行为提供独特的生化线索和生物物理信号。脱细胞ECM (dECM)是指从自然组织中获得的一类生物材料,经过脱细胞处理的组合,保留了ECM成分和消除细胞物质的固有结构。由于dECM具有全面模拟原始组织微环境的优越能力,因此被认为是重建功能三维组织模型最有前途的生物材料之一。在本章中,我们介绍了天然ecm的结构和功能作用,并总结了具有代表性的脱细胞和评价方法。我们还关注dECM在组织工程中的最新应用,使用传统方法(例如,可植入的薄片和可注射的水凝胶)和3D细胞打印技术。
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引用次数: 2
Chapter 16. Ethics of Using Human Cells/Tissues for 3D Tissue Models 第十六章。使用人体细胞/组织3D组织模型的伦理
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00329
J. Lim, D. Kim, S. H. Park, S. Kim
Three-dimensional (3D) human cell or tissue model systems provide a cellular microenvironment emulating native tissues in the human biology. These tissue engineering systems have been developed to investigate the efficacy and safety of new drugs, with the goal of conducting clinical trials of engineered human 3D tissues. Although research and commercialization are moving at a rapid pace, the ethical issues surrounding this technology have not been addressed on a commensurate time scale. The identification of the ethical concerns with this technology is not only a social responsibility but also in the interest of the future of this technology. Here, we discuss the ethical issues associated with human 3D tissue and organ modeling.
三维(3D)人体细胞或组织模型系统提供了一个细胞微环境,模拟人体生物学中的天然组织。这些组织工程系统的开发是为了研究新药的有效性和安全性,目的是进行工程人体3D组织的临床试验。尽管研究和商业化正在快速发展,但围绕这项技术的伦理问题尚未在相应的时间尺度上得到解决。识别这项技术的伦理问题不仅是一种社会责任,也是对这项技术未来的利益。在这里,我们讨论与人体三维组织和器官建模相关的伦理问题。
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引用次数: 0
Chapter 15. 3D Tissue Models for Toxicology 第15章。毒理学的3D组织模型
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00312
G. Skeldon, D. Hay, W. Shu
In chemical development, a product's potential toxic effects on life must be analysed before it can be used. This study of toxicology often utilises in vitro and in vivo models, but both have significant drawbacks. Current in vitro models are often simplistic and two-dimensional (2D), whereas in vivo models pose economic and ethical concerns. The burgeoning field of biofabrication has allowed production of more physiological relevant, three-dimensional (3D) in vitro models, which can reduce the use of animal models. This chapter will detail the various tissues that have been modelled in 3D for toxicology research using biofabrication, and their benefits over current 2D in vitro models.
在化学开发中,一种产品在使用前必须分析其对生命的潜在毒性影响。这种毒理学研究通常利用体外和体内模型,但两者都有明显的缺点。目前的体外模型通常是简单的二维(2D)模型,而体内模型则存在经济和伦理问题。蓬勃发展的生物制造领域已经允许生产更多生理相关的三维(3D)体外模型,这可以减少动物模型的使用。本章将详细介绍使用生物制造技术在3D中建模用于毒理学研究的各种组织,以及它们相对于当前2D体外模型的好处。
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引用次数: 0
Chapter 14. 3D Tissue Model of Cancers 第14章。癌症的三维组织模型
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00294
Y. Jung, H. Park, Kyuhwan Na, Hyunho Kim, Jihoon Yang, Seok Chung
From petri dish culture methods to 3D organoid generation, recent developments in modeling tissues in 3D have granted us the opportunity to explore more about cancer. In order to be part of a functional organism, individual cells require careful regulation of proliferation, differentiation, and survival. Cancer, however, does not require this regulation, therefore growing and dividing in uncontrolled manner that leads to malfunction within the body. Because of the chaotic characteristics of cancer, having a closely-mimicking cancer model is crucial. Even though many great discoveries have resulted from conventional culture methods of flask and petri dish, far greater and in vivo-like advancements have been achieved since the onset of 3D tissue modeling of cancer.
从培养皿培养方法到3D类器官生成,最近在3D组织建模方面的发展使我们有机会探索更多关于癌症的知识。为了成为功能性有机体的一部分,单个细胞需要仔细调节增殖、分化和存活。然而,癌症不需要这种调节,因此以不受控制的方式生长和分裂,导致体内功能障碍。由于癌症的混沌特性,拥有一个接近模拟癌症的模型至关重要。尽管传统的烧瓶和培养皿培养方法已经产生了许多伟大的发现,但自从癌症的3D组织建模开始以来,已经取得了更大的进展。
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引用次数: 0
Chapter 11. 3D Tissue Modeling of Skin Tissue 第十一章。皮肤组织的三维组织建模
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00233
Jun-ho Heo, Kyungha Kim, Suhyun Park, Noehyun Myung, Hyun-Wook Kang
The skin is the largest organ of the body. As it is the first line of defense from the external environment, it is the most vulnerable organ to injury. In 2016, there were 500 000 burn patients, and they incurred astronomical medical costs. Researchers have studied a wide range of treatments for skin injuries, including wound dressing, skin tissue engineering, and cell sheets. However, there are limitations to these treatments. They cannot regenerate the full thickness of the skin or heal extensive burn wounds. Many researchers are working towards developing skin bioprinting, which is a promising technology that can potentially be applied to overcome the limitations of current burn treatments. One of the key advantages of this technology is that it can be used to produce biomimetic artificial skin with multiple types of skin cells. Hence, various studies have been conducted using bioprinting technology to generate advanced biomimetic and functional skins containing vasculature, pigmentation, sweat glands and hair follicles. The resulting skin substitutes are expected to have a range of applications including cosmetics, skin disease modeling and drug development. In this chapter, we will review progress in bioprinting technology relating to manufacturing artificial skins.
皮肤是人体最大的器官。由于它是抵御外界环境的第一道防线,所以它是最容易受到伤害的器官。2016年,有50万烧伤患者,他们产生了天文数字的医疗费用。研究人员研究了广泛的皮肤损伤治疗方法,包括伤口敷料、皮肤组织工程和细胞片。然而,这些治疗方法也有局限性。它们不能再生皮肤的全部厚度,也不能治愈大面积的烧伤。许多研究人员正致力于开发皮肤生物打印技术,这是一项很有前途的技术,可以用于克服当前烧伤治疗的局限性。该技术的一个关键优点是,它可以用来制造具有多种类型皮肤细胞的仿生人造皮肤。因此,利用生物打印技术进行了各种研究,以生成含有脉管系统、色素沉着、汗腺和毛囊的高级仿生和功能性皮肤。由此产生的皮肤替代品预计将有一系列的应用,包括化妆品、皮肤病建模和药物开发。在本章中,我们将回顾与制造人造皮肤有关的生物打印技术的进展。
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引用次数: 0
Chapter 3. Microfluidic Platforms for Biofabrication and 3D Tissue Modeling 第三章。生物制造和三维组织建模的微流控平台
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00049
Minghao Nie, S. Takeuchi
The function of mammalian tissue relies greatly on the microscale tissue architecture into which specific types of cells are three-dimensionally arranged. To replicate these microscale tissue architectures and observe cell behaviors inside these architectures, techniques for handling, observing and stimulating the cells with microscale resolution are required; microfluidic technology—the technology that deals with the behavior, precise control, and manipulation of fluids that are geometrically constrained to a small scale—is one of the most promising candidate technologies for the fabrication and modeling of three-dimensional (3D) tissues with microscale architectures. In this book chapter, we report the recent progresses of biofabrication and 3D tissue modeling utilizing microfluidic platforms. We cover the applications of microfluidic platforms in the following two aspects: (1) microfluidic biofabrication platforms to fabricate microtissues such as cell-laden beads, cell-laden fibers and cell-laden sheets with high throughput and precise patterning of cells; (2) tissue-on-a-chip and organ-on-a-chip platforms to perform on-chip housing/installation, sensing and stimulation of tissues for 3D tissue modeling.
哺乳动物组织的功能在很大程度上依赖于微观尺度的组织结构,其中特定类型的细胞是三维排列的。为了复制这些微尺度的组织结构并观察这些结构中的细胞行为,需要以微尺度分辨率处理、观察和刺激细胞的技术;微流控技术是一种处理流体的行为、精确控制和操作的技术,这种技术在几何上被限制在一个小尺度上,是制造和建模具有微尺度结构的三维(3D)组织最有前途的候选技术之一。在本章中,我们报告了利用微流控平台进行生物制造和三维组织建模的最新进展。本文主要介绍了微流控平台在以下两个方面的应用:(1)利用微流控生物制造平台制备细胞负载珠、细胞负载纤维和细胞负载片等微组织,具有高通量和精确的细胞图案;(2)组织芯片和器官芯片平台,用于执行芯片上的组织外壳/安装,传感和刺激,用于3D组织建模。
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引用次数: 0
Chapter 6. Polymers in Biofabrication and 3D Tissue Modelling 第六章。生物制造和3D组织建模中的聚合物
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00119
F. Melchels
Biofabrication and 3D tissue modelling without employing polymers is near-unthinkable. The vast majority of biomaterials used in this field are polymeric in nature, and range from hard, synthetic polymers for structural integrity and mechanical support, to soft, water-swollen naturally-derived hydrogels that mimic the extracellular matrix and provide biochemical cues to encapsulated cells. This chapter aims to provide insights on the use of polymer biomaterials for biofabrication and 3D tissue modelling, going beyond an exhibit of examples found in literature. Its main focus is to elucidate how polymer properties govern their behaviour in the context of biofabrication and 3D tissue modelling, and to explain the functions they serve. This will not only explain why certain polymer biomaterials have been employed so far, but it will also guide future material selection and development towards specific applications.
不使用聚合物的生物制造和3D组织建模几乎是不可想象的。该领域中使用的绝大多数生物材料本质上都是聚合物,从用于结构完整性和机械支撑的硬合成聚合物到模拟细胞外基质并为被包裹细胞提供生化线索的软的、水膨胀的天然衍生水凝胶。本章旨在提供关于使用聚合物生物材料进行生物制造和3D组织建模的见解,超出了文献中发现的例子的展示。它的主要重点是阐明聚合物特性如何在生物制造和3D组织建模的背景下控制它们的行为,并解释它们所服务的功能。这不仅可以解释为什么某些高分子生物材料到目前为止被采用,而且还将指导未来材料的选择和发展,以实现特定的应用。
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引用次数: 0
Chapter 10. 3D Tissue Modelling of Orthopaedic Tissues 第十章。骨科组织的三维组织建模
Pub Date : 2019-01-02 DOI: 10.1039/9781788012683-00216
Ramya Bojedla, S. Chameettachal, Falguni Pati
Bones are organs of the skeletal system, providing shape, mechanical support and facilitating movement. They are well known for their self-healing abilities; however, large-scale bone defects cannot be healed completely by the body, and in most cases, external intervention is needed to repair the defects. Among different treatment options such as autografts and allografts, bone tissue engineering is becoming widespread. The essential idea is to apply the concepts of tissue engineering, i.e. the interplay of cells, scaffolds and biological molecules to form a ‘tissue engineering construct’ (TEC), which can promote bone repair and regeneration. The key players in bringing research and clinical practice together are the design and manufacturing technologies. The ability of 3D printing technology to make customized medical devices will make it the core manufacturing technology for bone tissue engineering in future generations.
骨骼是骨骼系统的器官,提供形状、机械支持和促进运动。它们的自我修复能力是众所周知的;然而,大面积的骨缺损不能由机体完全愈合,多数情况下需要外部干预来修复缺损。在不同的治疗选择中,如自体移植和同种异体移植,骨组织工程正变得越来越普遍。其基本思想是应用组织工程的概念,即细胞、支架和生物分子的相互作用,形成“组织工程结构”(TEC),可以促进骨修复和再生。将研究和临床实践结合在一起的关键参与者是设计和制造技术。3D打印技术制造定制医疗器械的能力将使其成为未来几代骨组织工程的核心制造技术。
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引用次数: 0
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