Artificial Neutrophils Against Vascular Graft Infection.

Abstract

Efficient neutrophil migration to infection sites plays a vital role in the body's defense against bacterial infections and natural immune responses. Neutrophils have a short lifespan and cannot be mass-cultured in vitro. Therefore, developing more stable artificial neutrophils (AN) in a controllable manner has become a research focus. However, existing AN lack chemotaxis, which is the ability to migrate toward high-signal-concentration positions in a dynamic blood- flow environment. Supplying AN with chemotaxis is key to designing AN that are more similar to natural neutrophils in terms of morphology and function. In this study, micrometer-sized, spherical, biocompatible AN are developed. These AN consist of zeolitic imidazolate framework-8 nanoparticles encapsulating two enzymes, coacervate droplet frameworks, and outer phospholipid bilayers carrying enzymes. The AN exhibit responsiveness to elevated hydrogen peroxide levels at inflammation sites, actively chemotaxing toward these sites along concentration gradients. They also demonstrate effective combat against Staphylococcus aureus infections. The capabilities of the AN are further validated through in vitro experiments and in vivo evaluations using vascular graft infection models. This study replicates natural neutrophils in terms of chemical composition, functionality, and physiological impact. It introduces new ideas for advancing the development of advanced artificial cells.