SOLID FREEFORM-FABRICATED SCAFFOLDS DESIGNED TO CARRY MULTICELLULAR MESENCHYMAL STEM CELL SPHEROIDS FOR CARTILAGE REGENERATION
SOLID FREEFORM-FABRICATED SCAFFOLDS DESIGNED TO CARRY MULTICELLULAR MESENCHYMAL STEM CELL SPHEROIDS FOR CARTILAGE REGENERATION
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DOI：
10.22203/ecm.v026a13
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发表时间：
2013-07-01
影响因子：
3.1
通讯作者：
Hsu, S. -h.
中科院分区：
文献类型：
--
作者：
Huang, G. -S.;Tseng, C. -S.;Hsu, S. -h.
三维（3D）细胞球体最近出现了一个新的趋势，以取代悬浮的单细胞在现代细胞为基础的治疗，因为他们更大的体外再生能力。在微环境变化期间，它们可能会失去3D结构，这对它们在体内的翻译带来了挑战。此外，传统的微孔支架可能难以容纳这些相对较大的球体。在这里，我们揭示了一种新颖的微环境设计，用于提供和维持3D球体。采用固体自由成型法（SFF），以聚（D，L-丙交酯-共-乙交酯）溶液为原料，制备了可容纳间充质干细胞（MSC）球体的大孔生物可降解支架。在空气等离子体处理后，用壳聚糖对它们的内表面进行改性，以保持球状体的形态。结果表明，与相同支架中的单细胞相比，加载在SFF支架中的人MSC球状体在体外和NOD/SCID小鼠中产生显著更大量的软骨相关细胞外基质。将MSC球形负载支架植入兔膝关节软骨缺损中显示出上级的软骨再生。本研究建立了新的观点，在体内应用的组织工程支架内的球体维持微环境的设计。
Three-dimensional (3D) cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC) spheroids were made by solid freeform fabrication (SFF) from the solution of poly(D,L-lactide-co-glycolide). Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.