Sci Transl Med:组织工程半月板的研究成果

2019-04-13 不详 北大医学部

近日,北京大学第三医院运动医学研究所江东和余家阔教授在Science Translational Medicine上发表了题为“Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus”的研究成果。

近日,北京大学第三医院运动医学研究所江东和余家阔教授在Science Translational Medicine上发表了题为“Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus”的研究成果。

半月板是膝关节内的纤维软骨结构,具有重要的缓冲和保护软骨作用。半月板撕裂后难以自愈,无论是撕裂本身,还是磨损碎裂或手术部分切除和全切除,都会导致胫骨和股骨之间的接触应力增大,明显增加膝关节骨关节炎发生的风险。

应用半月板假体(包括胶原半月板CMI)治疗半月板部分切除和全切除后的功能和结构的重建,经证明无法达到预期效果。同种异体半月板移植物的来源有限,远期效果不确切。因此,为解决半月板缺失后的功能和结构重建,人们对组织工程半月板(TEM)寄予了厚望。

然而,基于半月板所处的股骨和胫骨之间的运动环境和牵拉挤压力学环境的特殊性,体外培育的TEM存在强度不足、结构不仿生等劣势,导致其植入后转归较差。构建具有足够力学强度和天然半月板异质性结构的TEM是半月板研究领域亟待解决的难题。

本研究以聚己内酯(PCL)作为基质材料,使用3D打印技术制备了TEM支架(提供结构调控),与骨髓间充质干细胞(MSCs)复合后构建MSCs-PCL支架复合体;采用自主研发的可控动态应力加压装置模拟体内半月板受力情况,协同和增强细胞因子CTGF/TGF-β3对细胞-支架复合体上间充质干细胞的增殖分化作用(提供力学和化学调控),经三种因素联合调控培养4周后初步实现了干细胞的体外区域性诱导分化。植入动物体内24周后,再生半月板接近正常半月板的异质性结构和力学强度,有效预防了半月板切除后的关节软骨退变。

本研究提出一种新颖的异质性组织构建模式,利用支架结构、力学和生长因子微环境的协同作用,调控干细胞在支架不同部位的差异性分化,从而实现异质性组织工程半月板的构建和对关节软骨的保护,为其临床转化奠定了基础。

原始出处:

Zhang ZZ,et al.Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus.Sci Transl Med. 2019 Apr 10;11(487). pii: eaao0750.

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