Three-dimensional osteogenic and chondrogenic systems to model osteochondral physiology and degenerative joint diseases.
Three-dimensional osteogenic and chondrogenic systems to model osteochondral physiology and degenerative joint diseases.
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DOI：
10.1177/1535370214539232
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Tuan RS
中科院分区：
文献类型：
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作者：
Alexander PG;Gottardi R;Lin H;Lozito TP;Tuan RS
组织工程构建体有潜力作为正常组织功能和疾病发病机制的体外临床前模型，用于药物筛选和毒性评估。有效的高通量检测需要具有明确定义的性能参数的最小系统。这些系统必须准确地模拟人体器官的结构和功能及其对不同刺激的生理反应。肌肉骨骼组织在这方面提出了独特的挑战，因为它们是承重的、富含基质的组织，其功能与细胞外基质及其组织密切相关。临床上特别重要的是骨软骨连接处，它是退行性关节疾病（例如骨关节炎（OA））中受影响的目标组织，它由与软骨下骨密切相互作用的透明关节软骨组成。在这篇综述中，我们概述了当前可用的模拟天然生理学的骨和软骨组织工程体外三维系统，以及这些系统的实用性和局限性。具体来说，我们解决了将骨、软骨和其他组织结合起来形成交互式微生理系统（MPS）的需求，以充分捕捉关节骨软骨连接处的生物复杂性和机械功能。强调了三维 MPS 在肌肉骨骼生物学和医学中的潜在应用。
Tissue engineered constructs have the potential to function as in vitro pre-clinical models of normal tissue function and disease pathogenesis for drug screening and toxicity assessment. Effective high throughput assays demand minimal systems with clearly defined performance parameters. These systems must accurately model the structure and function of the human organs and their physiological response to different stimuli. Musculoskeletal tissues present unique challenges in this respect, as they are load-bearing, matrix-rich tissues whose functionality is intimately connected to the extracellular matrix and its organization. Of particular clinical importance is the osteochondral junction, the target tissue affected in degenerative joint diseases, such as osteoarthritis (OA), which consists of hyaline articular cartilage in close interaction with subchondral bone. In this review, we present an overview of currently available in vitro three-dimensional systems for bone and cartilage tissue engineering that mimic native physiology, and the utility and limitations of these systems. Specifically, we address the need to combine bone, cartilage and other tissues to form an interactive microphysiological system (MPS) to fully capture the biological complexity and mechanical functions of the osteochondral junction of the articular joint. The potential applications of three-dimensional MPSs for musculoskeletal biology and medicine are highlighted.