Defect-Engineered Tetragonal ZrO2 Nanoparticles for Biomaterial Interfaces: Green Synthesis, Biointerfacial Interactions, and SERS Biosensing.

Zirconia (ZrO2) is a widely used biomaterial in dental and orthopedic applications due to its excellent biocompatibility, chemical stability, and mechanical properties. However, the role of defect structure and phase composition in governing biomolecule-surface interactions at the biointerface remains insufficiently understood. In this work, we demonstrate a synthesis-driven strategy for engineering defect-rich tetragonal ZrO2 nanoparticles via conventional wet-chemical and plant-extract-mediated green routes using Laurus nobilis, Salvia rosmarinus, and Ficus benghalensis. Plant-mediated synthesis using rosemary extract promotes the formation of phase-pure tetragonal ZrO2 with increased surface heterogeneity and a higher density of oxygen vacancy-related defect states. To probe biomolecule-surface interactions, surface-enhanced Raman spectroscopy (SERS) measurements were performed using L-phenylalanine as a model system. This approach provides a simplified model of amino acid adsorption relevant to early-stage protein-surface interactions. Defect-rich tetragonal ZrO2 exhibits enhanced SERS response driven by charge-transfer interactions associated with oxygen vacancies and surface states. This represents one of the first demonstrations of amino-acid-based probing of zirconia SERS substrates in a biomaterial-relevant context, extending beyond conventional symmetric aromatic probe systems. In addition, the materials exhibit photocatalytic activity, interpreted as defect-driven surface reactivity and the ability to generate reactive oxygen species relevant for antibacterial functionality and prevention of biofilm formation at biomaterial interfaces in clinical environments. Overall, this work establishes a structure-property-function framework linking synthesis strategy with defect structure and interfacial performance, providing a framework for the rational design of zirconia-based biomaterials with controlled biointerface functionality.