Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland.
Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Ireland; Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Acta Biomater. 2021 May;126:1-14. doi: 10.1016/j.actbio.2021.03.016. Epub 2021 Mar 9.
The modest clinical impact of musculoskeletal tissue engineering (TE) can be attributed, at least in part, to a failure to recapitulate the structure, composition and functional properties of the target tissue. This has motivated increased interest in developmentally inspired TE strategies, which seek to recapitulate key events that occur during embryonic and post-natal development, as a means of generating truly biomimetic grafts to replace or regenerate damaged tissues and organs. Such TE strategies can be substantially enabled by emerging biofabrication and bioprinting strategies, and in particular the use of cellular aggregates, microtissues and organoids as 'building blocks' for the development of larger tissues and/or organ precursors. Here, the application of such biological building blocks for the engineering of musculoskeletal tissues, from vascularised bone to zonally organised articular cartilage, will be reviewed. The importance of first scaling-down to later scale-up will be discussed, as this is viewed as a key component of engineering functional grafts using cellular aggregates or microtissues. In the context of engineering anatomically accurate tissues of scale suitable for tissue engineering and regenerative medicine applications, novel bioprinting modalities and their application in controlling the process by which cellular aggregates or microtissues fuse and self-organise will be reviewed. Throughout the paper, we will highlight some of the key challenges facing this emerging field. STATEMENT OF SIGNIFICANCE: The field of bioprinting has grown substantially in recent years, but despite the hype and excitement it has generated, there are relatively few examples of bioprinting strategies producing implants with superior regenerative potential to that achievable with more traditional tissue engineering approaches. This paper provides an up-to-date review of emerging biofabrication and bioprinting strategies which use cellular aggregates and microtissues as 'building blocks' for the development of larger musculoskeletal tissues and/or organ precursors - a field of research that can potentially enable functional regeneration of damaged and diseased tissues. The application of cellular aggregates and microtissues for the engineering of musculoskeletal tissues, from vascularised bone to zonally organised articular cartilage, will be reviewed. In the context of engineering anatomically accurate tissues of scale, novel bioprinting modalities and their application in controlling the process by which cellular aggregates or microtissues self-organise is addressed, as well as key challenges facing this emerging field.
骨骼肌组织工程的临床效果并不显著，这至少部分归因于未能复制目标组织的结构、组成和功能特性。这促使人们对受发育启发的组织工程策略产生了更大的兴趣，这些策略试图复制胚胎和产后发育过程中发生的关键事件，以此生成真正仿生的移植物来替代或再生受损的组织和器官。新兴的生物制造和生物打印策略，特别是使用细胞聚集体、微组织和类器官作为更大组织和/或器官前体的“构建块”，可以极大地促进这些组织工程策略。在这里，将回顾这些生物构建块在工程化骨骼肌组织中的应用，从血管化骨到区域组织化关节软骨。将讨论先缩小规模后扩大规模的重要性，因为这被视为使用细胞聚集体或微组织工程功能性移植物的关键组成部分。在工程化适合组织工程和再生医学应用的解剖学上准确的、具有一定规模的组织的背景下，将回顾新型生物打印模式及其在控制细胞聚集体或微组织融合和自组织过程中的应用。在整篇论文中，我们将重点介绍该新兴领域面临的一些关键挑战。
意义声明：近年来，生物打印领域发展迅速，但尽管引起了轰动和兴奋，与更传统的组织工程方法相比，具有更好再生潜力的生物打印策略产生的植入物相对较少。本文提供了对新兴生物制造和生物打印策略的最新综述，这些策略使用细胞聚集体和微组织作为更大的骨骼肌组织和/或器官前体的“构建块”——这一研究领域有可能实现受损和患病组织的功能性再生。将回顾使用细胞聚集体和微组织作为构建块来开发更大的骨骼肌组织和/或器官前体的新兴生物制造和生物打印策略，包括从血管化骨到区域组织化关节软骨的工程化。在工程化具有精确解剖结构的组织的背景下，解决了新型生物打印模式及其在控制细胞聚集体或微组织自组织过程中的应用，以及该新兴领域面临的关键挑战。
