NIR-responsive 4D-Printed smart microneedle patches for on-demand transdermal drug administration

Microneedles (MNs) have emerged as a superior alternative to traditional delivery systems, offering enhanced absorption, improved bioavailability, and the convenience of self-administration, thereby enhancing patient compliance. Despite these advantages, current designs often lack personalization and fail to provide the precise, controllable, extended-release profiles and, importantly, on-demand release required for many therapeutic applications. Here, we present a vat-based four-dimensional (4D)-printed MN patch engineered for light-triggered, on-demand, long-term drug release. We incorporated a photothermal agent, molybdenum diselenide nanosheets (ML-MoSe 2 ), synthesized via eco-friendly liquid-phase exfoliation (LPE) using lentil protein extract. Three formulations were evaluated: 15 % PEGDA (polyethylene glycol diacrylate) and 7 % SFMA (silk fibroin methacrylate) (PEGDA-SFMA); PEGDA-SFMA with 0.1 % ML-MoSe 2 (NP/PEGDA-SFMA); and a composite of PEGDA-SFMA with ML-MoSe 2 -loaded agarose microparticles (MP/PEGDA-SFMA). The resulting arrays exhibited optimal swelling for skin adhesion and robust mechanical integrity for effective penetration, as confirmed by force-per-needle measurements and ex vivo testing. Specifically, the agarose-embedded ML-MoSe 2 formulation enabled an on-demand drug release mechanism triggered by 808 nm near-infrared laser irradiation. In vitro assessments confirmed excellent cytocompatibility with fibroblasts, keratinocytes, and endothelial cells, while further promoting the migration of fibroblasts and keratinocytes. These findings suggest that this 4D-printed smart MN platform is a highly promising candidate for controllable, on-demand long-term transdermal therapy and other similar biomedical applications.