Surface Engineering of Central Venous Catheters via Combination of Antibacterial Endothelium‐Mimicking Function and Fibrinolytic Activity for Combating Blood Stream Infection and Thrombosis

Abstract

Long‐term blood‐contacting devices (e.g., central venous catheters, CVCs) still face the highest incidence of blood stream infection and thrombosis in clinical application. To effectively address these complications, this work reports a dual‐functional surface engineering strategy for CVCs by organic integration of endothelium‐mimicking and fibrinolytic functions. In this proposal, a lysine (Lys)/Cu2+‐incorporated zwitterionic polymer coating (defined as PDA/Lys/Cu‐SB) is designed and robustly fabricated onto commercial CVCs using a facile two‐step process. Initially, adhesive ene‐functionalized dopamine is covalently reacted with Lys and simultaneously coordinated with bactericidal Cu2+ ions, leading to the deposition of a PDA/Lys/Cu coating on CVCs through mussel foot protein inspired surface chemistry. Next, zwitterionic poly(sulfobetaine methacrylate) (pSB) brushes are grafted onto the PDA/Lys/Cu coating to endow lubricant and antifouling properties. In the final PDA/Lys/Cu‐SB coating, endothelium‐mimicking function is achieved by combining the catalytic generation of nitric oxide from the chelated Cu2+ with antifouling pSB brushes, which led to significant prevention of thrombosis, and bacterial infection in vivo. Furthermore, the immobilized Lys with fibrinolytic activity show remarkably enhanced long‐term anti‐thrombogenic properties as evidenced in vivo by demonstrating the capability to lyse nascent clots. Therefore, this developed strategy provides a promising solution for long‐term blood‐contacting devices to combat thrombosis and infection.

A robust mixed-charge zwitterionic polyurethane coating integrated with antibacterial and anticoagulant functions for interventional blood-contacting devices

“…36 Importantly, it was observed that the CMPU coating did not contribute to an additional foreign-body inflammatory response owing to its biocompatible zwitterionic interface. 11,41 This indicates that the CMPU coating not only possesses antibacterial properties but also exhibits favorable biocompatibility, making it a promising candidate for applications where minimizing bacterial infection and inflammatory response are crucial.…”

“…5–9 Though systemic administration of antibiotics and anticoagulants has been a routine clinical protocol to mitigate infection and thrombosis, associated risks of post-operative bleeding, antibiotic resistance, and liver burden remain significant clinical concerns. 10–12 To replace the administration of antibiotics and anticoagulants, surface modification of blood-contacting devices with antifouling properties to effectively resist proteins, bacteria, and platelets has become a promising strategy to prevent infection and thrombosis. 13…”

Generalized Multifunctional Coating Strategies Based on Polyphenol-Amine-Inspired Chemistry and Layer-by-Layer Deposition for Blood Contact Catheters

“…Central venous catheters (CVCs), among other blood-contacting catheters, hold significant importance in the management of cardiovascular disease and cancer. − Typically, materials such as silicone rubber (SR), thermoplastic polyurethane, and polyurethane are employed in the construction of CVCs. ,− These materials are preferred due to their exceptional biocompatibility, resistance to high temperatures, and corrosion resistance. ,− Nevertheless, protein, bacterial, and platelet adhesion in the bloodstream can lead to thrombosis and bacterial infections. ,, These issues mainly arise from the catheter’s inappropriate wettability and the lack of antimicrobial properties. , These challenges can significantly burden patients, potentially leading to treatment failure or even mortality. ,, A common clinical strategy for the treatment of infection and thrombosis is to give antibiotics and intravenous heparin (Hep) immediately before or after catheter implantation, which often faces problems such as the development of resistant organisms and thrombocytopenia due to excess Hep . Consequently, the development of antibacterial and anticoagulant catheters remains a formidable undertaking.…”

Piezoelectrically-activated antibacterial catheter for prevention of urinary tract infections in an on-demand manner

“…However, silver ion hydrophilic coating catheters cannot be adjusted according to infection conditions [ 14 ], and clinically, their antimicrobial effectiveness does not appear significant [ 15 ]. Antibiotic-eluting catheters have shown some improvement, but there are problems of antibiotic resistance and rapid depletion [ [16] , [17] , [18] ]. Some promising antimicrobial methods have not yet been widely used in the clinic, such as antimicrobial peptide (AMP) coated catheters.…”