Swellable Gelatin Methacryloyl Microneedles for Extraction of Interstitial Skin Fluid toward Minimally Invasive Monitoring of Urea

Urea, the main nitrogenous waste product of protein metabolism, is eliminated almost exclusively by the kidney, and hence, displays considerable clinical significance in the assessment of kidney disorders. The aim of this study is to prepare and investigate the potential of swellable cross-linked gelatin methacryloyl (c-GelMA) microneedles (MNs) as a platform for minimally invasive extraction of interstitial skin fluid (ISF) toward straightforward point-of-care healthcare monitoring of renal complaints, by quantification of urea. c-GelMA MNs are successfully prepared by photo-cross-linking and micromolding, faithfully replicating the master molds (387 +/- 16 mu m height, 200 mu m base and 500 mu m tip-to-tip distance). These MN patches display good mechanical properties, withstanding more than 0.15 N per needle without breaking. Ex vivo skin insertion assays reveal that the MNs penetrate up to 237 mu m depth, reaching the dermis, where they should extract ISF considering a real application. In an in vitro application using an agarose skin model system, the c-GelMA MNs are able to efficiently recover urea (>98%). Additionally, these MNs exhibit noncytotoxic effects toward human keratinocytes. These findings suggest that c-GelMA MNs are promising devices for sampling ISF and offline analysis of urea, opening new avenues for simple point-of-care healthcare monitoring.