Single-Step Fabrication of Computationally Designed Microneedles by Continuous Liquid Interface Production

TLDR

Microneedles are painlessly puncturing arrays that enable transdermal delivery of hard‑to‑administer drugs, yet design parameters such as size, shape, spacing, and composition are difficult to modify with conventional microfabrication. The study introduces Continuous Liquid Interface Production (CLIP) to rapidly prototype sharp microneedles with tunable geometries. CLIP enables mold‑independent, one‑step fabrication of microneedle arrays in under 10 minutes, demonstrated with square‑pyramidal needles made from trimethylolpropane triacrylate, polyacrylic acid, and photopolymerizable PEG and PCL derivatives. The fabricated CLIP microneedles successfully pierced ex vivo murine skin and released a fluorescent drug surrogate.

Abstract

Microneedles, arrays of micron-sized needles that painlessly puncture the skin, enable transdermal delivery of medications that are difficult to deliver using more traditional routes. Many important design parameters, such as microneedle size, shape, spacing, and composition, are known to influence efficacy, but are notoriously difficult to alter due to the complex nature of microfabrication techniques. Herein, we utilize a novel additive manufacturing ("3D printing") technique called Continuous Liquid Interface Production (CLIP) to rapidly prototype sharp microneedles with tuneable geometries (size, shape, aspect ratio, spacing). This technology allows for mold-independent, one-step manufacturing of microneedle arrays of virtually any design in less than 10 minutes per patch. Square pyramidal CLIP microneedles composed of trimethylolpropane triacrylate, polyacrylic acid and photopolymerizable derivatives of polyethylene glycol and polycaprolactone were fabricated to demonstrate the range of materials that can be utilized within this platform for encapsulating and controlling the release of therapeutics. These CLIP microneedles effectively pierced murine skin ex vivo and released the fluorescent drug surrogate rhodamine.