Bio-orthogonal functionalization of bacterial cellulose combining metabolic glycoengineering and click chemistry

Bacterial cellulose possesses excellent biocompatibility and mechanical strength but lacks the bioactivity needed for many biomedical and healthcare applications. To address this limitation, we develop a metabolic glycoengineering-click chemistry strategy that enables in situ incorporation of azide groups into bacterial cellulose, followed by mild and selective conjugation of alkyne-bearing functional molecules. This approach avoids harsh chemical treatments, preserves the native properties of bacterial cellulose, and supports stable attachment of diverse bioactive agents, including antibacterial porphyrins, arginine-glycine-aspartic acid peptides, and recombinant proteins with fluorescent or enzymatic functions. As a proof-of-concept, a cascade catalytic system comprising glucose oxidase and superoxide dismutase is immobilized onto azide-modified bacterial cellulose, yielding a multifunctional wound dressing designed to address hyperglycemia and oxidative stress-key barriers to chronic wound healing. In male diabetic mice, this glucose oxidase/superoxide dismutase-integrated bacterial cellulose dressing (low endotoxin <0.1 EU/mL) accelerates wound closure to 92.1% by day 14, significantly outperforming the controls. Our strategy highlights a scalable and bio-orthogonal route for enhancing bacterial cellulose with user-defined bioactivities, thereby expanding its utility in advanced biomaterials development.