Engineering Detachable Hyaluronic Acid Microneedles for Controlled Intradermal Delivery of Particulate and Molecular Colorants: Influence of Matrix Cross-Linking and Particle Size

Controlled intradermal placement of colorants remains a challenge in materials research due to the competing effects of molecular solubility, particle size, and matrix interactions on retention and diffusion, with implications for medical reconstructive marking and aesthetic applications. In this study, we evaluate a detachable hyaluronic acid (HA) microneedle platform as a delivery system for depositing a diverse set of colorants spanning multiple chemical classes. Microneedle patches were fabricated from HA and loaded with fifteen colorants, including conventional synthetic pigments, Food, Drug, and Cosmetic (FD&C) dyes, natural pigments, and natural dyes. All formulations demonstrated sufficient mechanical strength (withstanding up to 70 N) to enable reliable insertion into ex vivo porcine skin and reproducible transfer of colorant-loaded needles. Comparative assessment revealed that conventional synthetic pigments produced the most vivid and spatially stable intradermal patterns, whereas molecular dyes exhibited broader diffusion and reduced pattern persistence. Pigment particle size emerged as a key determinant of local retention: intermediate-sized particles (3–5 µm) yielded sharper and more persistent patterns than smaller particulates. Furthermore, increasing the cross-linking density of the HA matrix effectively restricted the diffusion of hydrophobic dyes, providing a materials-based strategy for tuning the spatial precision of intradermal deposits. These findings establish a rational design framework for tailoring intradermal delivery systems to meet specific requirements for precision, duration, and visual outcome in dermatological and reconstructive procedures.