Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York.
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York.
J Biomed Mater Res B Appl Biomater. 2019 Aug;107(6):2019-2029. doi: 10.1002/jbm.b.34293. Epub 2018 Dec 13.
Synovium-derived mesenchymal stem cells (SMSCs) are an emerging cell source for regenerative medicine applications, including osteochondral defect (OCD) repair. However, in contrast to bone marrow MSCs, scaffold compositions which promote SMSC chondrogenesis/osteogenesis are still being identified. In the present manuscript, we examine poly(ethylene) glycol (PEG)-based scaffolds containing zonally-specific biochemical cues to guide SMSC osteochondral differentiation. Specifically, SMSCs were encapsulated in PEG-based scaffolds incorporating glycosaminoglycans (hyaluronan or chondroitin-6-sulfate [CSC]), low-dose of chondrogenic and osteogenic growth factors (TGFβ1 and BMP2, respectively), or osteoinductive poly(dimethylsiloxane) (PDMS). Initial studies suggested that PEG-CSC-TGFβ1 scaffolds promoted enhanced SMSC chondrogenic differentiation, as assessed by significant increases in Sox9 and aggrecan. Conversely, PEG-PDMS-BMP2 scaffolds stimulated increased levels of osteoblastic markers with significant mineral deposition. A "Transition" zone formulation was then developed containing a graded mixture of the chondrogenic and osteogenic signals present in the PEG-CSC-TGFβ1 and PEG-PDMS-BMP2 constructs. SMSCs within the "Transition" formulation displayed a phenotypic profile similar to hypertrophic chondrocytes, with the highest expression of collagen X, intermediate levels of osteopontin, and mineralization levels equivalent to "bone" formulations. Overall, these results suggest that a graded transition from PEG-CSC-TGFβ1 to PEG-PDMS-BMP2 scaffolds elicits a gradual SMSC phenotypic shift from chondrocyte to hypertrophic chondrocyte to osteoblast-like. As such, further development of these scaffold formulations for use in SMSC-based OCD repair is warranted. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2019-2029, 2019.
滑膜衍生间充质干细胞（SMSCs）是再生医学应用中新兴的细胞来源，包括骨软骨缺损（OCD）修复。然而，与骨髓间充质干细胞不同，促进 SMSC 软骨生成/成骨的支架成分仍在确定中。在本手稿中，我们研究了含有区域特异性生化线索的聚乙二醇（PEG）基支架，以指导 SMSC 骨软骨分化。具体来说，将 SMSC 包封在包含糖胺聚糖（透明质酸或软骨素-6-硫酸盐[CSC]）的 PEG 基支架中，低剂量的软骨和成骨生长因子（TGFβ1 和 BMP2），或成骨诱导性聚二甲基硅氧烷（PDMS）。初步研究表明，PEG-CSC-TGFβ1 支架通过 Sox9 和聚集蛋白聚糖的显著增加促进了 SMSC 软骨分化的增强。相反，PEG-PDMS-BMP2 支架刺激了成骨标志物水平的增加，并伴有明显的矿化沉积。然后开发了一个“过渡”区配方，其中包含存在于 PEG-CSC-TGFβ1 和 PEG-PDMS-BMP2 构建体中的软骨和成骨信号的分级混合物。“过渡”配方中的 SMSC 显示出与肥大软骨细胞相似的表型特征，胶原 X 的表达最高，骨桥蛋白的表达中等，矿化水平与“骨”配方相当。总体而言，这些结果表明，从 PEG-CSC-TGFβ1 到 PEG-PDMS-BMP2 支架的分级转变引发了 SMSC 表型从软骨细胞向肥大软骨细胞向成骨样细胞的逐渐转变。因此，进一步开发这些支架配方用于基于 SMSC 的 OCD 修复是有必要的。©2018 Wiley Periodicals，Inc. J Biomed Mater Res Part B：Appl Biomater 107B：2019-2029，2019。
