Amyloid-Templated Ceria Nanozyme Reinforced Microneedle for Diabetic Wound Treatments

Abstract

Amyloid fibrils have emerged as excellent templates and building blocks for the development of ordered functional materials with considerable potential in biomedical applications. Here, lysozyme amyloid fibrils (Lys-AFs) are employed as templates for the in situ synthesis of ceria nanozymes (Lys-AFs-Ceria) with ultrafine dimensions, an optimized Ce³⁺/Ce⁴⁺ ratio, and uniform distribution on the fibril surface, addressing the challenges of low catalytic efficiency and high susceptibility to aggregation typical of traditional methods. As a proof of concept, it is further applied Lys-AFs-Ceria to develop hydrogel/microneedle for treating bacteria-infected diabetic wounds via non-covalent interactions between polyphenols and amyloid fibrils incorporating glucose oxidase (GOX). The hydrogel/microneedle facilitates superoxide dismutase and catalase cascade catalysis by Lys-AFs-Ceria, and integrates GOX-mediated glucose consumption, synergistically achieving glucose reduction, reactive oxygen species elimination, and hypoxia alleviation in the diabetic wound infection microenvironment. In addition to antibacterial properties and tissue regeneration promotion of Lys-AFs scaffold, Lys-AFs-Ceria regulates macrophages polarization toward an anti-inflammatory M2 state. Collectively, these attributes contribute to the enhanced efficacy of diabetic wound healing, with in vivo studies demonstrating increased healing efficiency following a single application, and more in general an effective strategy toward high-catalytic and stable nanozymes.

Keywords: amyloid fibrils; ceria nanozymes; diabetic wound; microenvironment regulation; microneedle.