Artificial feeding of ticks: a 3Rs-based approach for studying tick biology, pathogen transmission and drug discovery.

Abstract Ticks are globally significant ectoparasites and vectors of pathogens that cause substantial human and animal health and economic burdens, including diseases such as Lyme borreliosis, babesiosis, and anaplasmosis. Research on tick biology and pathogen transmission has traditionally relied on live animal models, such as sheep, rabbits, and rodents. While effective, these in vivo approaches raise ethical, logistical, and biological concerns, particularly considering the 3Rs principles (Replacement, Reduction, and Refinement) in biomedical research. Artificial tick feeding systems (ATFS) have recently emerged as a promising alternative, aligning with the 3Rs by enabling controlled feeding of both soft and hard ticks under defined conditions while reducing reliance on live animals. This review critically appraises ATFS research published between 1912 and 2024 ( n = 206 studies), classifying systems into capillary feeding, membrane feeding, and semi-automated platforms. Although membrane feeding dominates the field, limitations include prolonged feeding periods in hard ticks, microbial contamination, high mortality, perturbation of the tick microbiome, challenges with species-specific optimisation, and long-term laboratory colony maintenance of hard ticks. We highlight key advances, persisting challenges, and future directions to refine ATFS and its application to improve our understanding of tick–pathogen interactions, accelerate development of novel vaccines, therapeutics, and integrated control strategies.