From surface to bulk modification: Plasma polymerization of amine-bearing coating by synergic strategy of biomolecule grafting and nitric oxide loading

Integration of two or more biomolecules with synergetic and complementary effects on a material surface can help to obtain multi-functions for various biomedical applications.However,the amounts of biomolecules integrated and their physiological functions are compromised due to the limited surface anchoring sites.Herein,we propose a novel concept of film engineering strategy“from surface to bulk synergetic modification”.This new concept is realized by employing the surface amine groups of plasma polymerized allylamine(PPAm)film for grafting a molecule e.g.,thrombin inhibitor,bivalirudin(BVLD),meanwhile its bulk amine groups is used as a universal depot for storing and releasing therapeutic nitric oxide(NO)gas as supplement to the functions of BVLD.It is demonstrated that such a“from surface to bulk synergetic modification”film engineering can impart the modified-substrates with anti-platelet and anti-coagulant dual functions,giving rise to a highly endotheliummimetic thromboresistant property.We believe that our research provides a very promising strategy to deliver multifunctional surface versatilely that require NO release in combination with other properties,which will find broad biomedical applications in blood-contacting devices,and et al.Moreover,it also provides a brand-new film engineering strategy for tailoring surface multi-functionalities of a wide range of materials.

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

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.