Overcoming Challenges in Engineering Large, Scaffold-Free Neocartilage with Functional Properties
Overcoming Challenges in Engineering Large, Scaffold-Free Neocartilage with Functional Properties
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DOI：
10.1089/ten.tea.2017.0495
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发表时间：
2018-11-01
影响因子：
4.1
通讯作者：
Athanasiou, Kyriacos A.
中科院分区：
文献类型：
--
作者：
Huang, Brian J.;Brown, Wendy E.;Athanasiou, Kyriacos A.
尽管已经描述了许多软骨工程方法，但很少有报道产生大于4cm的构建体（2），这是基于细胞的治疗所考虑的典型病变大小。此外，目前基于细胞的疗法仅针对局灶性病变，而大的非孤立性病变的治疗仍然是一个需求很大的领域。本研究的目的是将自组装新软骨的制造从0.2cm（2）的标准尺寸扩大到大于8cm（2）。传代的绵羊关节软骨细胞自组装成5或25 mm直径的无支架新软骨结构。直径为25 mm的结构长至9.3 cm（2）（面积比例放大23），具有与直径为5 mm的结构相似的特性;不幸的是，这些大型结构变形，无法用作潜在的植入物。一种新的新软骨制造策略，采用机械限制，一分钟的自重，和化学刺激（细胞松弛素D，TGF-1，软骨素-ABC和赖氨酰氧化酶样2蛋白）被发现成功地产生大（25毫米直径）的结构与平面，均匀的形态。化学刺激增加胶原蛋白含量和拉伸杨氏模量140%和240%的25毫米直径的结构和30%和70%的5毫米直径的结构，分别。这项研究不仅证明了机械和化学刺激的适当组合可以产生非常大的自组装新软骨，而且还保持甚至增强了其特性。
Although numerous cartilage engineering methods have been described, few report generation of constructs greater than 4cm(2), which is the typical lesion size considered for cell-based therapies. Furthermore, current cell-based therapies only target focal lesions, while treatment of large nonisolated lesions remains an area of great demand. The objective of this study was to scale up fabrication of self-assembled neocartilage from standard sizes of 0.2cm(2) to greater than 8cm(2). Passaged sheep articular chondrocytes were self-assembled into 5 or 25-mm-diameter scaffoldless neocartilage constructs. The 25-mm-diameter constructs grew up to 9.3cm(2) (areal scale-up of 23) and possessed properties similar to those of the 5-mm-diameter constructs; unfortunately, these large constructs were deformed and are unusable as a potential implant. A novel neocartilage fabrication strategyemploying mechanical confinement, a minute deadweight, and chemical stimulation (cytochalasin D, TGF-1, chondroitinase-ABC, and lysyl oxidase-like 2 protein)was found to successfully generate large (25-mm diameter) constructs with flat, homogeneous morphologies. Chemical stimulation increased collagen content and tensile Young's modulus 140% and 240% in the 25-mm-diameter constructs and 30% and 70% in the 5-mm-diameter constructs, respectively. This study not only demonstrated that exceedingly large self-assembled neocartilage can be generated with the appropriate combination of mechanical and chemical stimuli but also that its properties were maintained or even enhanced.