Monitoring biomarkers and pharmacokinetics is crucial for the precise diagnosis and treatment of chronic skin diseases. Dermal interstitial fluid (ISF) presents an attractive alternative source of biomarkers and drugs to blood; however, a simple, efficient, and comfortable extraction method is lacking. Here, we combine high-precision 3D printing and micromolding to develop an ultrasonic-powered, replaceable hexagram-shaped hydrogel microneedle (HMN) patch. Hexagram-shaped HMNs exhibit superior mechanical strength and faster ISF extraction rates compared to cone, pyramid, and octagram shapes. The patch, attached to a holder and integrated with a commercial ultrasonic device via a customized connector, allows easy replacement after use. With ultrasound assistance, the patch extracts over 15 mu L, 6 mu L, and 4 mu L of ISF from porcine skin ex vivo, healthy mouse skin, and psoriatic mouse skin in vivo, respectively, within 1 min. The recovered ISF, obtained via centrifugation from HMNs, is used to monitor the dermal pharmacokinetics of drugs (e.g., methotrexate) and psoriasis-related biomarkers (e.g., interleukin-17 and -22) in mouse models, showing trends comparable to those detected via skin biopsy and blood draw. This ultrasonic-powered, replaceable hexagram-shaped HMN patch holds great promise for advancing the diagnosis, treatment, and research of skin diseases.
