Wang Yung-Li, Lin Shih-Pei, Nelli Srinivasa Rao, Zhan Fu-Kai, Cheng Hsun, Lai Tsung-Sheng, Yeh Mei-Yu, Lin Hsin-Chieh, Hung Shih-Chieh
Institute of Clinical Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu, 300, Taiwan.
Macromol Biosci. 2017 Apr;17(4). doi: 10.1002/mabi.201600192. Epub 2016 Oct 28.
Fluorenyl-9-methoxycarbonyl (Fmoc)-diphenylalanine (Fmoc-FF) and Fmoc-arginine-glycine--aspartate (Fmoc-RGD) peptides self-assemble to form a 3D network of supramolecular hydrogel (Fmoc-FF/Fmoc-RGD), which provides a nanofibrous network that uniquely presents bioactive ligands at the fiber surface for cell attachment. In the present study, mesenchymal stem cells (MSCs) in Fmoc-FF/Fmoc-RGD hydrogel increase in proliferation and survival compared to those in Fmoc-FF/Fmoc-RGE hydrogel. Moreover, MSCs encapsulated in Fmoc-FF/Fmoc-RGD hydrogel and induced in each defined induction medium undergo in vitro osteogenic, adipogenic, and chondrogenic differentiation. For in vivo differentiation, MSCs encapsulated in hydrogel are induced in each defined medium for one week, followed by injection into gelatin sponges and transplantation into immunodeficient mice for four weeks. MSCs in Fmoc-FF/Fmoc-RGD hydrogel increase in differentiation into osteogenic, adipogenic, and chondrogenic differentiation, compared to those in Fmoc-FF/Fmoc-RGE hydrogel. This study concludes that nanofibers formed by the self-assembly of Fmoc-FF and Fmoc-RGD are suitable for the attachment, proliferation, and multi-differentiation of MSCs, and can be applied in musculoskeletal tissue engineering.
芴甲氧羰基（Fmoc）-二苯基丙氨酸（Fmoc-FF）和芴甲氧羰基-精氨酸-甘氨酸-天冬氨酸（Fmoc-RGD）肽自组装形成超分子水凝胶的三维网络（Fmoc-FF/Fmoc-RGD），该网络提供了一个纳米纤维网络，能在纤维表面独特地呈现生物活性配体以促进细胞附着。在本研究中，与在芴甲氧羰基-二苯基丙氨酸/芴甲氧羰基-精氨酸-甘氨酸-谷氨酸（Fmoc-FF/Fmoc-RGE）水凝胶中的间充质干细胞（MSC）相比，芴甲氧羰基-二苯基丙氨酸/芴甲氧羰基-精氨酸-甘氨酸-天冬氨酸水凝胶中的MSC增殖和存活率增加。此外，封装在芴甲氧羰基-二苯基丙氨酸/芴甲氧羰基-精氨酸-甘氨酸-天冬氨酸水凝胶中的MSC在每种特定诱导培养基中诱导后会发生体外成骨、成脂和成软骨分化。对于体内分化，将封装在水凝胶中的MSC在每种特定培养基中诱导一周，然后注射到明胶海绵中并移植到免疫缺陷小鼠体内四周。与芴甲氧羰基-二苯基丙氨酸/芴甲氧羰基-精氨酸-甘氨酸-谷氨酸水凝胶中的MSC相比，芴甲氧羰基-二苯基丙氨酸/芴甲氧羰基-精氨酸-甘氨酸-天冬氨酸水凝胶中的MSC向成骨、成脂和成软骨分化的能力增强。本研究得出结论，芴甲氧羰基-二苯基丙氨酸和芴甲氧羰基-精氨酸-甘氨酸-天冬氨酸自组装形成的纳米纤维适用于MSC的附着、增殖和多向分化，并可应用于肌肉骨骼组织工程。
