HAMA/GelMA-based hydrogel microneedle patch via DLP 3D bioprinting for high-efficiency ISF extraction

Microneedle (MN) technology is a promising minimally invasive tool for interstitial skin fluid (ISF) extraction. Hydrogel MN patches enable efficient ISF extraction. However, the traditional polydimethylsiloxane (PDMS) photopolymerization method has limitations in morphology control, accuracy, and susceptibility to process parameter interference, affecting MN strength and functional consistency. To address these challenges, we propose a composite hydrogel MN patch based on Digital Light Processing (DLP) 3D bioprinting of hyaluronic acid methacryloyl (HAMA)/gelatin methacryloyl (GelMA) for high-efficiency ISF transdermal extraction. The structure and performance of the MNs were improved by optimizing the bio-ink ratio and printing parameters. Adjusting the ratio of GelMA and HAMA improved the cross-linking structure, optimizing the mechanical properties and swelling performance of the composite hydrogel. Optimizing the light intensity and exposure time ensured consistent MN morphology, resulting in well-defined and evenly distributed needle tips. Controlled UV exposure avoided defects such as uneven cross-linking or brittleness. The results showed that when the HAMA-to-GelMA ratio was 8:2, the light intensity was 9 mW/cm², and the exposure time was 6 s, the MN patches demonstrated excellent microstructures and mechanical properties, with each MN enduring over 1.28 N and achieving a swelling rate above 1200 %. In vitro experiments verified effective penetration and ISF extraction, obtaining 8.5 mg of PBS in 1 min and successfully quantifying glucose concentration. In summary, this study establishes a robust MN patch with superior swelling performance and enhanced ISF extraction efficiency and provides a promising platform for minimally invasive diagnosis and real-time health monitoring.