Cold-sintered hybrid nanostructures for biomedical drug delivery: A nanomanufacturing pathway toward clinical translation

• Cold sintering integrates drugs, polymers, and ceramics in a single low-temp step • Hybrid nanostructures enable sustained release while preserving biomolecule activity • Material combinations include bioceramic–polymer, graphene, and magnetic composites • Potential applications span bone repair, cancer therapy, and wound healing • Aligns with sustainability, additive manufacturing, and personalized medicine Hybrid nanostructures have emerged as highly versatile platforms for biomedical drug delivery due to their ability to integrate inorganic and organic phases into multifunctional architectures. These systems offer advantages such as tunable drug release profiles, structural stability, and the potential for targeted therapeutic action. Despite these benefits, conventional fabrication methods often rely on high-temperature processes that limit scalability, energy efficiency, and compatibility with delicate bioactive agents. The Cold Sintering Process (CSP), a novel low-temperature densification technique, has recently gained attention as a sustainable alternative capable of addressing these limitations. By operating at ultralow temperatures under modest pressure, CSP preserves organic functionality, enhances structural integrity, and enables the production of hybrid nanostructures with retained biological activity. This review consolidates recent advances in hybrid nanostructures for drug delivery, emphasizing bone-related and load-bearing systems as key examples, while maintaining relevance to broader biomedical drug-delivery contexts. The discussion highlights structure-property relationships, processing-function correlations, and the role of CSP in designing next-generation biomaterials with enhanced biocompatibility, tunability, and clinical relevance. While bone and load-bearing systems are used as representative platforms, the CSP approach introduced here provides a generalizable framework for fabricating multifunctional drug-delivery devices across diverse biomedical environments. Challenges related to reproducibility, scale-up, and regulatory translation are critically assessed. Finally, future research directions are proposed to integrate CSP into nanomanufacturing pipelines for biomedical applications. By bridging nanomanufacturing, biomaterials, and drug delivery, this work positions CSP as a transformative processing strategy for enabling multifunctional hybrid systems in healthcare.