Department of Orthopaedics (Division of Sports Medicine), University of Miami, Miller School of Medicine, Miami, FL, 33136, USA; Diabetes Research Institute & Cell Transplant Center, University of Miami, Miller School of Medicine, Miami, FL, 33136, USA.
Department of Orthopaedics, Orthopaedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, OH, 44195, USA; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Semin Cell Dev Biol. 2017 Feb;62:67-77. doi: 10.1016/j.semcdb.2016.07.013. Epub 2016 Jul 13.
Articular cartilage is a highly specialized tissue whose remarkable properties of deformability, resistance to mechanical loading, and low-friction gliding are essential to joint function. Due to its role as a cushion in bone articulation, articular cartilage is subject to many types of damaging insults, including decades of wear and tear, and acute joint injuries. However, this built-for-life tissue has a very poor intrinsic ability in adulthood to durably heal defects created by damaging insults. Consequently, articular cartilage progressively deteriorates and is eventually eroded, exposing the subchondral bone to the joint space, triggering inflammation and osteophyte development, and generating severe pain and joint incapacitation. The disease is called osteoarthritis (OA) and is today the leading cause of pain and disability in the human population. Researchers and clinicians have worked for decades to develop strategies to treat OA and restore joint function, but they are still far from being able to offer patients effective preventive or restorative treatments. Novel ideas, knowledge and technologies that nurture hope for major new breakthroughs are therefore sought. In this review, we first outline the composition, structure, and functional properties of normal human adult articular cartilage, as a reference for tissue conservation and regenerative strategies. We then describe current options that have been used clinically and in pre-clinical trials to treat osteoarthritic patients, and we discuss the benefits and inadequacies of these treatment options. Next, we review research efforts that are currently ongoing to try and achieve durable repair of functional cartilage tissue. Methods include engineering of tissue implants and we discuss the needs and options for tissue scaffolds, cell sources, and growth and differentiation factors to generate de novo or repair bona fide articular cartilage.
关节软骨是一种高度特化的组织,其显著的可变形性、抗机械载荷能力和低摩擦滑动特性对于关节功能至关重要。由于它在骨关节中的缓冲作用,关节软骨容易受到多种类型的损伤,包括数十年的磨损和急性关节损伤。然而,这种为生命而设计的组织在成年后具有非常差的内在能力,可以持久地修复损伤引起的缺陷。因此,关节软骨逐渐恶化,最终被侵蚀,使软骨下骨暴露于关节间隙,引发炎症和骨赘形成,并产生严重的疼痛和关节功能丧失。这种疾病称为骨关节炎(OA),是当今人类疼痛和残疾的主要原因。研究人员和临床医生几十年来一直致力于开发治疗 OA 和恢复关节功能的策略,但仍远不能为患者提供有效的预防或恢复性治疗。因此,人们正在寻找新的想法、知识和技术,以期取得重大突破。在这篇综述中,我们首先概述了正常人类成年关节软骨的组成、结构和功能特性,作为组织保存和再生策略的参考。然后,我们描述了目前临床上和临床前试验中用于治疗骨关节炎患者的选择方案,并讨论了这些治疗选择的优缺点。接下来,我们回顾了目前正在努力实现功能性软骨组织持久修复的研究工作。方法包括组织植入物的工程化,我们讨论了组织支架、细胞来源以及生长和分化因子的需求和选择,以生成真正的关节软骨。