(Nanowerk Spotlight) Each year, millions of people miss crucial vaccine booster shots, undermining the effectiveness of immunization programs worldwide. The challenge stems from a fundamental limitation: most vaccines require multiple doses spread over months to generate lasting immunity, yet healthcare systems struggle to ensure patients return for each shot. Previous attempts to create single-dose vaccines that automatically release boosters have produced inconsistent results, largely due to manufacturing constraints that restrict vaccine-containing structures to basic shapes with imprecise release timing.
A team of researchers from Imperial College London and the University of Oxford has developed a solution that brings unprecedented precision to vaccine delivery. Their technique uses specialized 3D printing at the nanoscale to create tiny, hollow particles that can hold and release vaccines according to carefully controlled specifications. These particles, smaller than the width of a human hair, can be engineered to release their contents at specific times and rates—potentially eliminating the need for return visits to complete a vaccine series.
The researchers detail their innovation in Advanced Materials (“Nanoscale Biodegradable Printing for Designed Tuneability of Vaccine Delivery Kinetics”), describing a new class of printing materials they named Spatiotemporal Controlled Release Inks of Biocompatible polyEsters (SCRIBE). These materials work with a printing process called two-photon polymerization, where focused laser light triggers chemical reactions that transform liquid resin into solid structures with features as small as 500 nanometers—about 200 times thinner than a human hair.
Hollow microparticle design and microfabrication. a) Anatomy of an optimized hollow microparticle with porthole-controlled release with SEM micrographs of (i) XZ- and (ii) XY-plane cutaways. b) A handheld 49-particle batch for perspective. c) Microfabrication process overview. d) Brightfield image of a single particle after CF647-OVA loading and washing and e) after sealing. f) SEM of sealed particles ready for detachment and injection. All scale bars = 100 μm. (Image: Reprinted from DOI:10.1002/adma.202417290, CC BY)
The foundation of SCRIBE is a modified version of poly(lactic-co-glycolic acid), or PLGA, a biodegradable material already approved for medical use. The team engineered this material to work with high-precision 3D printing while maintaining control over how quickly it breaks down in the body. By adjusting both the chemical composition and physical structure of the printed particles, they can fine-tune exactly when and how quickly vaccines are released.
The printed particles resemble microscopic hollow spheres with walls ranging from one to twenty-five micrometers thick, depending on the desired release rate. Each sphere contains a carefully designed chamber for holding vaccines, sealed with a precisely engineered porthole that regulates the rate at which the vaccine escapes as the surrounding material gradually dissolves.
Testing their system with a model protein called ovalbumin, the researchers demonstrated three distinct release patterns. Fast-releasing particles delivered their entire contents within two weeks. Medium-speed particles released their cargo steadily over eight weeks. Slow-releasing versions maintained controlled delivery for up to ten weeks.
These varying release rates proved crucial for tailoring immune responses. Fast-releasing particles triggered strong initial immunity but required boosters to maintain protection. Slow-releasing particles produced more gradual but longer-lasting immune responses. When the researchers combined quick-release and sustained-release particles in a single injection, they achieved immunity levels matching traditional multi-shot vaccination schedules.
The precision of this approach extends beyond timing. Unlike previous methods limited to simple shapes, SCRIBE enables the creation of complex geometric features that further control how vaccines interact with the body. The researchers can adjust particle size, wall thickness, and internal architecture to optimize delivery for different vaccines and desired immune responses.
The system’s versatility stems from its dual controls over both physical structure and chemical composition. By mixing different chemical components into the printing material, the team can accelerate or slow down how quickly the particles degrade. This chemical tuning works in concert with the physical design to achieve precise release profiles impossible with existing technologies.
Laboratory tests confirmed that vaccines remained stable inside the particles for extended periods, addressing a critical concern for delayed-release systems. The particles also showed no signs of causing inflammation during the study period when tested in animals, suggesting good biological compatibility.
The research establishes a new technical foundation for single-dose vaccines, though significant work remains before clinical use becomes possible. The team must verify the approach works with actual vaccines rather than just model proteins. Manufacturing processes need refinement to produce particles in quantities suitable for widespread use.
This printing technique may also find applications beyond vaccines. The ability to create microscopic containers with precisely controlled release properties could benefit other medical treatments requiring careful dosing over time. The researchers are exploring potential uses in cancer therapy, hormone treatments, and other areas where timing and dosage precision are crucial.
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