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Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions.

ABSTRACT: Application of extracorporeal circuits and indwelling medical devices has saved many lives. However, it is accompanied with two major complications: thrombosis and infection. To address this issue, we apply therapeutic nitric oxide gas (NO) and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions. Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions (Cu-DOTA) and dibenzylcyclooctyne- (DBCO-) modified antimicrobial peptide based on carbodiimide and click chemistry respectively. The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth, but also catalytically generate NO from endogenous s-nitrosothiols (RSNO) to reduce adhesion and activation of platelets, preventing the formation of thrombus. We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices, with reduced clinical complications associated with thrombosis and infection.

SUBMITTER: Yu H

PROVIDER: S-EPMC7695912 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions.

Yu Han H Yu Shaoxing S Qiu Hua H Gao Peng P Chen Yingzhong Y Zhao Xin X Tu Qiufen Q Zhou Minggang M Cai Lin L Huang Nan N Xiong Kaiqin K Yang Zhilu Z

Bioactive materials 20201123 6

Application of extracorporeal circuits and indwelling medical devices has saved many lives. However, it is accompanied with two major complications: thrombosis and infection. To address this issue, we apply therapeutic nitric oxide gas (NO) and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions. Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10 ...[more]

PMID: 33294738

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Project description:Upon the osteoporotic condition, sluggish osteogenesis, excessive bone resorption, and chronic inflammation make the osseointegration of bioinert titanium (Ti) implants with surrounding bone tissues difficult, often lead to prosthesis loosening, bone collapse, and implant failure. In this study, we firstly designed clickable mussel-inspired peptides (DOPA-N3) and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions. Then, two dibenzylcyclooctyne (DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain (BMP-2) were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction. We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1. In vitro, the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells (MSCs), and conspicuous immunopolarization-regulation to shift macrophages to alternative (M2) phenotypes and inhibit inflammation, as well as enhancement of osseointegration and mechanical stability in osteoporotic rats. In summary, our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants, which was conducive to the long-term success of Ti implants, especially in the osteoporotic or inflammatory conditions. Graphical abstract Mussel-inspired adhesion and bio-orthogonal reactions are combined for surface modification of Ti-based implants with RGD peptide and BMP-2 peptide. Dual-functionalized Ti-based implants can enhance osteogenesis and osseointegration through promoting BMSCs adhesion and osteodifferentiation, as well as modulate macrophage polarization in the osteoporotic rats.Image 1 Highlight • A clickable mussel-inspired peptide and two DBCO-capped bioactive peptides for facile decoration of Ti prostheses via robust catechol/TiO2 coordinative interactions and click chemical reaction.• Dual functionalized Ti-based surface can improve cell anchoring and osteogenicitity by rationally adjusting the grafting ratio of BMP-2 and RGD peptides.• Dual functionalized Ti-based surface synergistically achieve M2 shifting and efficient inflammation inhibition for osseointegration.

Dataset Information

Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions.

Publications

Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions.

Similar Datasets

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