Click functionalized, tissue-specific hydrogels for osteochondral tissue engineering.

Click functionalized, tissue-specific hydrogels for osteochondral tissue engineering.
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DOI:
10.1002/jbm.a.36848
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发表时间:
2020-03
期刊:
Journal of biomedical materials research. Part A
影响因子:
--
通讯作者:
Mikos AG
Mikos AG
中科院分区:
其他
文献类型:
--
作者:
Guo JL;Li A;Kim YS;Xie VY;Smith BT;Watson E;Bao G;Mikos AG

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骨软骨修复需要同时诱导关节软骨和软骨下骨的发育,这就需要为这些高度不同的组织呈现多种组织特异性线索。为了提供一种独特的水凝胶系统来修复任何一种组织类型,我们开发了生物功能化的间充质干细胞水凝胶,它可以通过简单的点击修饰交联剂聚乙醇酸-聚乙二醇-聚乙醇酸-二(BUT-2-yne-1,4-dithiol)(PdBT),为软骨形成或成骨提供原位生化信号。在用软骨特异性生物分子(N-钙粘素多肽、硫酸软骨素)或骨特异性生物分子(骨髓归巢肽1、甘氨酸-组氨酸-赖氨酸肽)修饰PdBT后,生物功能化的PdBT-交联水凝胶可以选择性地促进所需的骨或软骨样基质合成和组织特异性基因表达,其效果取决于生物分子的选择和浓度。我们的发现建立了这种点击功能化水凝胶系统的多功能性,以及它在体外促进骨软骨组织表型发展的能力。
Osteochondral repair requires the induction of both articular cartilage and subchondral bone development, necessitating the presentation of multiple tissue-specific cues for these highly distinct tissues. To provide a singular hydrogel system for the repair of either tissue type, we have developed biofunctionalized, mesenchymal stem cell-laden hydrogels that can present in situ biochemical cues for either chondrogenesis or osteogenesis by simple click modification of a crosslinker, poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT). After modifying PdBT with either cartilage-specific biomolecules (N-cadherin peptide, chondroitin sulfate) or bone-specific biomolecules (bone marrow homing peptide 1, glycine-histidine-lysine peptide), the biofunctionalized, PdBT-crosslinked hydrogels can selectively promote the desired bone- or cartilage-like matrix synthesis and tissue-specific gene expression, with effects dependent on both biomolecule selection and concentration. Our findings establish the versatility of this click functionalized hydrogel system as well as its ability to promote in vitro development of osteochondral tissue phenotypes.
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