Nanoscale Buried Interface Control in Silicone Hydrogels Enables a Biointerface Engineering Platform

Engineering multifunctional biointerfaces requires quantitative understanding of how buried nanoscale coating architectures govern biological function, yet such relationships remain inaccessible because non-destructive characterization of soft, curved interfaces is lacking. Here, we establish an integrated engineering-characterization-function platform that quantitatively resolves buried nanocoatings and directly correlates their architecture with interfacial performance. Using silicone hydrogel contact lenses as a representative biomedical substrate, robust semi-interpenetrating polymer network (semi-IPN) nanocoatings are fabricated and characterized by gas cluster ion beam X-ray photoelectron spectroscopy (GCIB-XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and a newly developed atomic force microscopy (AFM) modulus-based algorithm. This multimodal framework non-destructively maps vertical chemical gradients, nanometer-scale layer thicknesses, and interfacial mechanical distributions with sub-100 nm precision, enabling quantitative visualization of conformal buried nanocoatings. The resulting structure-function relationships guide the rational engineering of poly(2-hydroxyethyl methacrylate) (poly(HEMA)) interfaces with homogeneous surface coverage (∼89%), enhanced wettability, markedly reduced protein adsorption and cellular fouling, while fully preserving oxygen permeability, optical transparency, UV protection, and mechanical integrity. The platform further enables incorporation of functional monomers for light-triggered therapeutic release without compromising device performance. Beyond contact lenses, this work provides a generalizable strategy for quantitatively engineering and predicting multifunctional nanocoatings across diverse biomedical interfaces.