Kinetoplastid infections, caused by Leishmania and Trypanosoma species, pose significant global health challenges, disproportionally affecting vulnerable populations in tropical regions. Despite the skin’s pivotal role as both an entry point and a reservoir for these parasites, the mechanistic understanding of host–parasite interactions at this interface remains limited.

Recent advancements in bioengineered skin models, such as full thickness skin equivalents and skin organoids, provide a promising complement to in vivo and ex vivo models. These in vitro systems address key challenges related to accessibility, reproducibility, and anatomical relevance, while potentially incorporating key tissue components, including immune cells and vascular structures. By replicating the complex structure of human skin at customizable levels of complexity, they offer powerful platforms for high-resolution studies of parasite–host interactions. Furthermore, by supporting natural vector transmission and enabling the simulation of diverse biological conditions, these systems open new avenues for investigating parasite development, tissue invasion, dissemination and immune dynamics.