The application of Green Chemistry principles to design novel eco-friendly materials for high-level radioactive waste (HLW) encapsulation offers a transformative approach to nuclear waste management. By aligning material development with sustainability goals, researchers can create geopolymers, metal-organic frameworks (MOFs), and bio-inspired ceramics that outperform conventional glass or cement matrices while minimizing environmental harm. Green Chemistry’s foundational principle of waste prevention (Principle #1) drives the use of industrial byproducts like fly ash in geopolymer synthesis, reducing reliance on virgin materials and cutting CO₂ emissions from traditional cement production. Atom economy (Principle #2) guides the design of MOFs with high actinide-uptake efficiency, ensuring maximal incorporation of radionuclides into their porous structures without excess reagents. The imperative to avoid hazardous synthesis (Principle #3) favors aqueous sol-gel routes for bio-ceramics like hydroxyapatite over toxic precursors, while safer solvent systems (Principle #5) replace conventional organic solvents in MOF fabrication with ionic liquids or supercritical CO₂. Energy efficiency (Principle #6) is inherent to geopolymers, which cure at ambient temperatures a stark contrast to the 1000°C+ vitrification processes used for borosilicate glass. Radiation-resistant material designs (Principle #4) incorporate nanocrystalline phases (e.g., spinel in geopolymers) to mitigate amorphization under prolonged α/γ radiation, addressing a critical limitation of current waste forms. Renewable feedstocks (Principle #7) such as chitosan-modified ceramics enhance durability through natural polymer networks, and catalytic additives (Principle #9) like TiO₂ nanoparticles accelerate geopolymer setting kinetics. Long-term stability (Principle #10) is achieved through crystalline ceramic matrices (e.g., pyrochlores) that resist aqueous corrosion over geological timescales, while embedded sensor-MOF hybrids (Principle #11) enable real-time monitoring of radionuclide leaching. Crucially, inherently safer chemistry (Principle #12) is realized through self-healing geopolymers with microencapsulated alkali-silicate solutions to autonomously repair radiation-induced cracks. Despite these advances, challenges persist: MOFs require defect engineering to withstand radiation, bio-inspired materials need scalable production methods, and all systems demand accelerated aging tests to project performance over millennia. By rigorously applying Green Chemistry’s framework, next-generation encapsulation materials can simultaneously achieve technical superiority and environmental sustainability transforming HLW disposal from an ecological liability into a model of circular economy innovation.

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