Bioactive prosthetic interface constructed with cascading multi-nanozyme hydrogel to induce M2 macrophage polarization and heal diabetic bone defects.

Abstract

Chronic oxidative stress and inflammation in diabetic microenvironments impede the healing of bone defects. Inflammation is prolonged by the decreased phenotypic transformation of M1 to M2 anti-inflammatory macrophages. To achieve catalytic cascading and immunomodulation, black phosphorus quantum dots (BPQDs) with photothermal properties and glucose oxidase activity were combined with copper metal-organic frameworks (Cu-MOFs) with superoxide dismutase-like and catalase-like activities that scavenge reactive oxygen species (ROS) to construct a hybrid nanozyme (BPQD@MOF). The system can quickly clear glucose while scavenging ROS and producing O₂, thereby alleviating local oxidative stress and inflammation, and can also exert bactericidal activity under photothermal stimulation. BPQD@MOF was added to an immunomodulatory hydrogel for the modification of a Ti-6Al-4V porous scaffold that not only mimicked the porosity and hardness of bone, but also used a soft hydrogel matrix with nanozymes to improve biological activity. This achieved self-cascading glucose consumption and ROS clearance, regulated metabolic reprogramming, and induced M2 macrophage polarization, which promoted osteogenic differentiation and accelerated bone healing in an in vivo model. This bioactive prosthetic interface design provides a potential treatment for diabetic bone defects.