Laccase-Mediated Fabrication of Food Packaging Films: A Critical Review of Functional Performance, Safety, and Industrial Viability.

Although natural biopolymers represent promising sustainable packaging alternatives, their weak mechanical and barrier properties limit industrial use. While previous reviews focus on descriptive aspects of enzymatic modification, this review fills a critical literature gap by systematically bridging molecular-level laccase-driven reactions with quantitative techno-economic and safety and regulatory frameworks. We evaluate the kinetic and topological differences between direct tyrosyl-coupled protein homopolymerisation and mediator-assisted 'graft-then-link' polysaccharide strategies. Crucially, we analyse how entrapment versus surface-immobilised architectures dictate mass-transfer regimes, establishing their specific functional fitness for active oxygen scavenging or intelligent time-temperature monitoring. Beyond physical performance, we critically assess the translational bottlenecks currently hindering industrial scaling. For the first time, we integrate a quantitative techno-economic analysis using the Technology Readiness Level (TRL) framework, demonstrating that active film fabrication costs (EUR 0.01-0.10/m2) are heavily offset by high-protein food waste savings (>EUR 2.00/kg). Finally, we navigate European and US regulatory landscapes for enzymatically active materials and evaluate safety risks via the Threshold of Toxicological Concern (TTC) model and deterministic migration modelling. This comprehensive analysis establishes a 'Safe-by-Design' paradigm, guiding the scalable development of intrinsically safe, high-performance biocatalytic packaging.