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    Mussel-Inspired and Bioclickable Peptide Engineered Surface to Combat Thrombosis and Infection

    Journal: Research, Volume 2022, APR 14

    Authors: Mou, Xiaohui; Zhang, Hongbo; Qiu, Hua; Zhang, Wentai; Wang, Ying; Xiong, Kaiqin; Huang, Nan; Santos, Helder A.; Yang, Zhilu

    Organizations: National Natural Science Foundation of China [82072072]; International Cooperation Project by Science and Technology Department of Sichuan Province [2021YFH0056, 2019YFH0103]; Fundamental Research Funds for the Central Universities [2682020ZT82, 2682020ZT76]

    Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices, leading to significant mortality in clinic. To address this issue, here, we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide, with bio-orthogonal click chemistry, to tailor the surface functionalities of tubing and catheters. Inspired by mussel adhesive foot protein, a bioclickable peptide mimic (DOPA)(4)-azide-based structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry. Then, the dibenzylcyclooctyne (DBCO) modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions and the DBCO-modified antimicrobial peptide (DBCO-AMP) are clicked onto the grafted surfaces via bio-orthogonal reaction. The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous s-nitrosothiols to resist adhesion/activation of platelets, thus preventing the formation of thrombosis. Overall, this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.
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