Bioactive‐Loaded Detachable Crosslinked Hyaluronic Acid Microneedles: Structural Validation and Clinical Anti‐Wrinkle Efficacy

Delivering a persistent biopolymer matrix to the superficial dermis remains a significant challenge for microneedle systems due to the inherent limitations of conventional dissolving platforms. Here, we present a detachable microneedle design that permits rapid needle separation during administration. To biologically compensate for the relatively short 350 μm needle geometry designed for at‐home safety, this system utilizes a crosslinked hyaluronic acid (cHA) matrix loaded with cosmetic peptides and functional excipients. The primary objective is to reliably deliver this composite biochemical cHA matrix into the skin to a depth of ~300 μm, which corresponds to the dermal–epidermal junction. Segmented mechanical compression analysis revealed that the non‐polymeric payload did not compromise the matrix; rather, it significantly improved the initial axial stiffness from 0.059 ± 0.004 to 0.081 ± 0.005 N/mm per needle. This structural enhancement minimized axial displacement under load, enabling the 350 μm needles to reliably reach an ex vivo penetration depth of 335 ± 22 μm. A 14‐day clinical evaluation ( n = 28) using three‐dimensional topography demonstrated excellent clinical tolerability with no adverse effects and significant reductions in surface roughness ( R a ) and maximum wrinkle height ( R t ) both immediately and at the conclusion of treatment.