Stem Cell-Recruiting Injectable Microgels for Repairing Osteoarthritis

Stem Cell-Recruiting Injectable Microgels for Repairing Osteoarthritis
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DOI:
10.1002/adfm.202105084
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发表时间:
2021-07-17
影响因子:
19
通讯作者:
Huang, Wei
Huang, Wei
中科院分区:
材料科学1区
文献类型:
--
作者:
Lei, Yiting;Wang, Yuping;Huang, Wei

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干细胞的分化潜力和活力在细胞分离和输送过程中常常受到损害。受到岛屿可以招募海鸟筑巢的现象的启发,利用微流体技术和光聚合工艺构建了“细胞岛”微凝胶(MG),即负载生长因子的甲基丙烯酸透明质酸和肝素混合MG,可以招募内源干细胞并促进软骨分化,然后采用非共价结合的血小板衍生生长因子-BB(PDGF-BB)和转化生长因子-β3 (TGF-β3)。 PDGF-BB和TGF-β3的负载效率分别为96%和91%。体外和体内实验发现,“细胞岛”MGs可以增强细胞的迁移能力,并通过释放PDGF-BB将细胞从其微环境中招募出来。同时,通过使用透明质酸,“细胞岛”MG为细胞附着和扩散提供了合适的微环境。此外,“细胞岛”MG 通过释放 TGF-β 3 诱导募集细胞的软骨分化,并对骨关节炎具有良好的治疗效果。总之,这种开发的“细胞岛”MG可能作为一个临时的“巢位”,允许内源干细胞迁移、粘附和分化,这可能是一个有希望的候选者,而不是传统的细胞接种支架,用于促进组织再生。
The differentiation potentials and viability of stem cells are often impaired during cell isolation and delivery. Inspired by the phenomenon where islands can recruit seabirds for nesting, "cell island" microgels (MGs), that is, growth factor-loaded methacrylated hyaluronic acid and heparin blend MGs, which can recruit endogenous stem cells and promote chondrogenic differentiation, are constructed using microfluidic technology and photopolymerization processes, followed by non-covalently binding platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta3 (TGF-beta 3). The loading efficiency of PDGF-BB and TGF-beta 3 are 96% and 91%, respectively. In vitro and in vivo experiments find that the "cell island" MGs can enhance the migratory capacity of cells and recruit them from their niche via releasing PDGF-BB. Meanwhile, by using hyaluronic acid, the "cell island" MGs provide a suitable microenvironment for cell attachment and spreading. Furthermore, the "cell island" MGs induce chondrogenic differentiation of the recruited cells via releasing TGF-beta 3 and present a promising therapeutic effect for osteoarthritis. In sum, this developed "cell island" MG might serve as a temporary "nest site" to allow the migration, adhesion, and differentiation of endogenous stem cells, which can be a promising candidate rather than the conventional cell-seeded scaffolds for promoting tissue regeneration.