While vaccines have traditionally been administered as injections into the muscle, administration by the intradermal route, that is, between the surface layers of the skin, has several notable advantages. Human skin is rich in immune cells, which means that a much lower dose can stimulate an equal immune response, lowering overall costs and improving access to vaccines in places where supply is limited.

Today, researchers at Stanford University, United States, and the University of North Carolina at Chapel Hill, United States, used a fast, light-based 3D printing process to create an intradermal micro-needle vaccine patch (PNAS, doi: 10.1073 / pnas.2102595118). When tested in mice, the patch resulted in more potent immune responses compared to traditional vaccination routes.

Faster 3D printing with light

Previously, Joseph M. DeSimone and his colleagues invented a new approach to 3D printing called continuous liquid interface production (CLIP) that offers fast manufacturing speeds and high resolution of features. In 2016, they used CLIP to successfully print micro needle patches with adjustable geometries within minutes.

CLIP works by projecting a continuous sequence of sectional UV images – generated by a 385nm light-emitting diode (LED) and digital light-processing imaging unit – through an oxygen-permeable and transparent window. UV. The window is located at the bottom of a bath of liquid resin, so that the cross-sectional images are able to harden the resin and build the object on a support plate that rises steadily.

“We can grow these objects continuously, without sticking to the window. The renewal of the resin occurs in the space between the part of the building and the window created by the oxygen passing through it, ”said DeSimone, study author and professor of translational medicine and chemical engineering at Stanford University. ” We call that [permanently liquid] rule out the “dead zone”. So this is a breakthrough in the way 3D printing is done.

A boost in the immune response

Researchers had to significantly fine-tune their CLIP printer to achieve the appropriate length scale for vaccine delivery via a microneedle patch, which consists of an array of solid needle projections the size of a micrometer. But the principles behind CLIP have remained the same, and the dead zone has allowed for the creation of much smaller and more delicate structures. A traditional layer-by-layer stereolithography approach, on the other hand, would require breaking window structures every time.

DeSimone and his colleagues printed a 10 × 10 array of faceted microneedles with ridges to increase vaccine area and cargo compared to a square pyramid shape. When coated with vaccine components for in vivo In experiments, the intradermal patch generated an antibody immune response that was 10 times greater than injection into muscle and 50 times greater than injection under the skin in mice.

“It’s a whole new day for microneedle manufacturing because you can now reduce pixel size. In the paper we used a printer with 20 micron pixels. Here at Stanford, we’ve built a new printer with 1.5 micron pixels, ”he said. “So we’re making incredible new generations of microneedles where you can now create all kinds of architectural structures and really open up a wide range of performance. “