Advancing intradermal vaccine delivery: Focus on hollow microneedles and skin models

Intradermal (ID) vaccine administration is a promising alternative to intramuscular injection yet remains underused, as the classically employed Mantoux technique is difficult to perform consistently. Hollow microneedles (HMNs) offer a more user-friendly approach for liquid vaccine delivery but face issues such as inconsistent skin piercing and inefficient liquid injection. To address these issues, in the preclinical phase, skin models are used that mimic the mechanical, structural, and immunological properties of human skin as well as the interaction between skin and needle. However, current models often fail to capture the entire biological complexity. This review discusses recent findings, challenges, and engineering solutions for reliable HMN skin piercing and liquid injection, alongside emerging trends in skin model technologies for vaccine delivery. Unique to this review paper is the final perspective, which highlights how advances in skin model technologies can be leveraged to accelerate and de-risk HMN development, streamlining the preclinical phase.