Safeguarding Osteointegration in Diabetic Patients: A Potent 'Chain Armor' Coating for Scavenging ROS and Macrophage Reprogramming in a Microenvironment-Responsive Manner

摘要

Risk of implant failure increases profoundly in patients with pre-existing conditions (e.g., diabetes). Current therapies adopt a one-sided focus on the direct antibacterial properties of biomaterials and osteogenesis stimulation. However, in this study it is demonstrated that a "chain armor" structure (Ce-TA) that mainly targets the regulation of the local pathological microenvironment, provides a novel solution to scavenge reactive oxygen species (ROS) by simulating superoxide dismutase and catalase and significantly improving osteointegration under diabetic conditions. Ce-TA based on a metal phenolic network biological functional interface is successfully constructed. Ce-TA, an ultrathin armor structure, is biocompatible and facile. Through in vitro assays it is demonstrated that Ce-TA reshapes the diabetic microenvironment into a regenerative one in a microenvironment-responsive manner, where Ce-TA regulates hypoxia-inducible factor 1 alpha (HIF-1 alpha) activity by reducing the level of mitochondrial ROS, and effectively alleviates mitochondrial dysfunction and reprogrammes macrophages to a pro-healing state. Furthermore, it is confirmed that Ce-TA shows excellent therapeutic effects on the reducing postoperative infection and enhances osteointegration of intra-osseous implants in diabetic rat models. The proposed strategy opens up a promising opportunity for repurposing metals with intrinsic enzyme-like activity for the goal of enhancing the osteointegration of devices with orthopedic and dental applications among diabetic patients.