Optimizing snake fang-inspired microneedles for transdermal liquid drug delivery.

Transdermal microneedles (MNs) offer a minimally invasive and highly compliant approach for delivering macromolecular therapeutics. However, the clinical translation of conventional conical and pyramidal MNs is hindered by an intrinsic mechanical trade-off: minimizing tip diameter reduces insertion force but increases fracture susceptibility, whereas enlarging the base improves structural robustness at the cost of higher skin insertion resistance. Furthermore, closely spaced MN arrays frequently suffer from the "bed-of-nails" effect, which precludes adequate tissue penetration. Inspired by the open-groove fangs of opisthoglyphous snakes, which evolved for low-resistance tissue puncture, we designed and systematically optimized snake fang-inspired microneedles (SF-MNs). Using a three-layer hyperelastic Neo-Hookean skin model, we conducted finite element analyses on 27 distinct SF-MN configurations to evaluate their static strength and dynamic insertion mechanics. The optimal SF-MN structure (500 [Formula: see text] length, 30 [Formula: see text] groove depth, 10 [Formula: see text] tip diameter) demonstrated superior lateral structural stability (safety factor > 0.6) and achieved significantly lower insertion forces compared to size-matched conical MNs. Notably, SF-MN arrays mitigated the "bed-of-nails" effect, narrowing the critical inter-needle spacing triggering range to 396-402 [Formula: see text]-markedly lower than the 440-700 [Formula: see text] range of conventional arrays. By leveraging groove-induced tissue diversion and contact area reduction, these biomimetic arrays enable deeper skin penetration, offering a robust and highly efficient platform for transdermal drug delivery in chronic disease management.