Structure-Regulated Silk Fibroin Microneedle Patches for Minimally Invasive Glucose-Responsive Colorimetric Sensing.

Minimally invasive microneedle devices have emerged as highly promising platforms for localized interstitial fluid (ISF) sensing and biomarker detection. In this study, we present a bilayer silk fibroin microneedle system that leverages material structure regulation to achieve optimal mechanical strength, controlled swelling, and limited dissolution. Our dual-layer architecture spatially separates skin penetration and local interstitial-fluid access from the sensing region, improving reagent retention and enabling clear, localized colorimetric readouts. Furthermore, the incorporation of 2-hydroxypropyl-β-cyclodextrin stabilizes chromogenic substrates within the hydrophilic silk matrix, delivering robust responses both in vitro and in vivo. The optimized microneedles exhibit uniform morphology and sufficient compressive strength for reliable transdermal insertion, successfully producing visually distinguishable outputs in animal models. Ultimately, this material-guided, device-integrated platform highlights the tremendous potential of combining biomaterial engineering with microscale design for next-generation minimally invasive biosensors.