Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus
Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus
复制标题
精心策划的生物力学、结构和生化刺激，用于工程各向异性半月板
DOI：
10.1126/scitranslmed.aao0750
复制
发表时间：
2019
影响因子：
17.1
通讯作者：
Jiang Dong
中科院分区：
文献类型：
--
作者：
Zhang Zheng Zheng;Chen You Rong;Wang Shao Jie;Zhao Feng;Wang Xiao Gang;Yang Fei;Shi Jin Jun;Ge Zi Gang;Dingo Wen Yu;Yang Yu Chen;Zou Tong Qiang;Zhang Ji Ying;Yu Jia Kuo;Jiang Dong
利用生物力学、生物化学和结构线索设计的各向异性半月板在兔中显示了长期的膝关节软骨保护作用。工程各向异性半月板是关节内的纤维软骨结构，有助于减少关节运动期间的摩擦。膝关节半月板内的外部和内部区域在细胞类型、细胞外基质成分、组织和相应的机械性能（各向异性）方面有所不同。在这里，Zhang等人在间充质干细胞接种的聚合物支架的培养过程中使用生物力学刺激和生长因子处理，以产生模拟天然膝关节半月板的组织结构。当植入兔膝关节时，工程化半月板结构表现出长期的软骨保护作用。这项研究有助于指导组织工程的努力，以产生各向异性的结构。膝关节半月板的各向异性结构和适当功能的重建仍然是需要克服的重要挑战，因为半月板中带状组织组织的复杂性在承载和减震方面具有重要作用。目前用于半月板重建的组织工程解决方案未能在体内实现和维持适当的功能，因为它们产生了均匀的组织，导致长期的关节退化。为了应对这一挑战，我们将生物力学和生物化学刺激应用于接种到仿生支架中的间充质干细胞，以诱导纤维软骨细胞分化的空间调节，从而导致工程化半月板的生理各向异性。使用定制的动态拉伸-压缩加载系统结合两种生长因子，我们诱导了I型和II型胶原蛋白的区域性、层特异性表达，其结构和功能与天然半月板组织中存在的胶原蛋白相似。工程半月板在兔子模型中表现出对膝关节的长期软骨保护作用。本研究同时应用生物力学、生物化学和结构线索来实现半月板的各向异性重建，证明了各向异性工程化半月板在体内长期膝关节软骨保护中的实用性。
Anisotropic meniscus engineered using biomechanical, biochemical, and structural cues demonstrates long-term knee chondroprotection in rabbits. Engineering anisotropy The meniscus is a fibrocartilage structure within a joint that helps reduce friction during joint movement. The outer and inner regions within the knee meniscus differ in cell types, extracellular matrix components, organization, and corresponding mechanical properties (anisotropy). Here, Zhang et al. used biomechanical stimulation and growth factor treatment during culture of mesenchymal stem cell–seeded polymer scaffolds to generate tissue constructs that mimic the native knee meniscus. The engineered meniscus constructs demonstrated long-term chondroprotection when implanted into the knees of rabbits. This study helps guide tissue engineering efforts to generate anisotropic constructs. Reconstruction of the anisotropic structure and proper function of the knee meniscus remains an important challenge to overcome, because the complexity of the zonal tissue organization in the meniscus has important roles in load bearing and shock absorption. Current tissue engineering solutions for meniscus reconstruction have failed to achieve and maintain the proper function in vivo because they have generated homogeneous tissues, leading to long-term joint degeneration. To address this challenge, we applied biomechanical and biochemical stimuli to mesenchymal stem cells seeded into a biomimetic scaffold to induce spatial regulation of fibrochondrocyte differentiation, resulting in physiological anisotropy in the engineered meniscus. Using a customized dynamic tension-compression loading system in conjunction with two growth factors, we induced zonal, layer-specific expression of type I and type II collagens with similar structure and function to those present in the native meniscus tissue. Engineered meniscus demonstrated long-term chondroprotection of the knee joint in a rabbit model. This study simultaneously applied biomechanical, biochemical, and structural cues to achieve anisotropic reconstruction of the meniscus, demonstrating the utility of anisotropic engineered meniscus for long-term knee chondroprotection in vivo.