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Growth factor-mimicking 3,4-dihydroxyphenylalanine-encoded bioartificial extracellular matrix like protein promotes wound closure and angiogenesis
Biomaterials Science ( IF 6.6 ) Pub Date : 2020-10-20 , DOI: 10.1039/d0bm01379j
Meganathan Ilamaran 1, 2, 3, 4 , Ashokraj Sundarapandian 1, 2, 3, 4 , Mayilvahanan Aarthy 1, 2, 3, 4 , Ganesh Shanmugam 2, 3, 4, 5 , Ganesan Ponesakki 1, 2, 3, 4 , Kamini Numbi Ramudu 1, 2, 3, 4 , Ayyadurai Niraikulam 1, 2, 3, 4
Affiliation  

The present work reports a new route to prepare a “smart biomaterial” by mimicking long-acting cellular growth factor showing enhanced cell–material interactions by promoting cell proliferation and angiogenesis. For that, reactive non-proteogenic amino acid 3,4-dihydroxyphenylalanine (DOPA) was genetically introduced into an intrinsic triple-helical hierarchical structure forming protein to initiate hierarchical self-assembly to form a macromolecular structure. The self-assembled scaffold displayed vascular endothelial growth factor mimicking the pro-angiogenic reactive group for repairing and remodeling of damaged tissue cells. We customized the recombinant collagen-like protein (CLP) with DOPA to promote rapid wound healing and cell migrations. Selective incorporation of catechol in variable and C-terminal region of CLP enhanced interaction between inter- and intra-triple-helical collagen molecules that resulted in a structure resembling higher-order native collagen fibril. Turbidity analysis indicated that the triple-helical CLP self-assembled at neutral pH via a catechol intra-crosslinking mechanism. After self-assembly, only DOPA-encoded CLP formed branched filamentous structures suggesting that catechol mediated network coordination. The catechol-encoded CLP also acted as a “smart material” by mimicking long-acting cellular growth factor showing enhanced cell–material interactions by promoting cell proliferation and angiogenesis. It eliminates release rate, stability, and shelf-life of hybrid growth factor conjugated biomaterials. The newly synthesized CLP has the potential to promote accelerated cell migration, pro-angiogenesis, and biocompatibility and could be used in the field of implantable medical devices and tissue engineering.

中文翻译:

模仿3,4-二羟基苯丙氨酸的生长因子编码的生物人工细胞外基质(如蛋白质)促进伤口闭合和血管生成

The present work reports a new route to prepare a “smart biomaterial” by mimicking long-acting cellular growth factor showing enhanced cell–material interactions by promoting cell proliferation and angiogenesis. For that, reactive non-proteogenic amino acid 3,4-dihydroxyphenylalanine (DOPA) was genetically introduced into an intrinsic triple-helical hierarchical structure forming protein to initiate hierarchical self-assembly to form a macromolecular structure. The self-assembled scaffold displayed vascular endothelial growth factor mimicking the pro-angiogenic reactive group for repairing and remodeling of damaged tissue cells. We customized the recombinant collagen-like protein (CLP) with DOPA to promote rapid wound healing and cell migrations. Selective incorporation of catechol in variable and C-terminal region of CLP enhanced interaction between inter- and intra-triple-helical collagen molecules that resulted in a structure resembling higher-order native collagen fibril. Turbidity analysis indicated that the triple-helical CLP self-assembled at neutral pH 通过儿茶酚内部交联机制。自组装后,仅DOPA编码的CLP形成分支的丝状结构,表明儿茶酚介导了网络协调。邻苯二酚编码的CLP还通过模仿长效细胞生长因子来充当“智能材料”,该生长因子通过促进细胞增殖和血管生成而增强了细胞与材料的相互作用。它消除了杂化生长因子偶联生物材料的释放速率,稳定性和保质期。新合成的CLP具有促进加速细胞迁移,促血管生成和生物相容性的潜力,可用于可植入医疗设备和组织工程领域。
更新日期:2020-11-03
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