Development of an automated biomaterial platform to study mosquito feeding behavior

Abstract

Mosquitoes carry a number of deadly pathogens that are transmitted while feeding on blood through the skin, and studying mosquito feeding behavior could elucidate countermeasures to mitigate biting. Although this type of research has existed for decades, there has yet to be a compelling example of a controlled environment to test the impact of multiple variables on mosquito feeding behavior. In this study, we leveraged uniformly bioprinted vascularized skin mimics to create a mosquito feeding platform with independently tunable feeding sites. Our platform allows us to observe mosquito feeding behavior and collect video data for 30–45 min. We maximized throughput by developing a highly accurate computer vision model (mean average precision: 92.5%) that automatically processes videos and increases measurement objectivity. This model enables assessment of critical factors such as feeding and activity around feeding sites, and we used it to evaluate the repellent effect of DEET and oil of lemon eucalyptus-based repellents. We validated that both repellents effectively repel mosquitoes in laboratory settings (0% feeding in experimental groups, 13.8% feeding in control group, p < 0.0001), suggesting our platform’s use as a repellent screening assay in the future. The platform is scalable, compact, and reduces dependence on vertebrate hosts in mosquito research.

Artificial Feeding Systems for Vector-Borne Disease Studies

“…Engineered Biocompatible Constructs: These are artificial materials carefully designed to replicate the structure and properties of the mammalian skin [ 18 , 155 , 156 ]. The constructs consist of crosslinked polymer networks with the ability to absorb and retain substantial amounts of water, imparting a soft, flexible, and gel-like structure that is similar to host skin [ 155 , 157 , 158 , 159 , 160 , 161 ].…”

“…These characteristics render them a viable alternative for delivering blood meals in vector-borne pathogen studies, closely mirroring the natural feeding conditions experienced by vectors in the wild [ 156 ]. The integration of engineered human tissue into these biocompatible constructs has facilitated investigations into the mechanical characteristics of the skin and the activities of vectors, notably mosquitoes, during feeding processes [ 18 , 155 ].…”

“…Recent advancements in mosquito feeding behavior studies have seen the emergence of two innovative systems utilizing engineered biocompatible constructs. One system employs bio-printed vascularized skin mimics designed to replicate natural feeding conditions, establishing a controlled environment for in-depth investigations into mosquito feeding behavior [ 18 ]. This platform demonstrated its capabilities through the successful evaluation of repellent effects, positioning it as a promising tool for future repellent screening assays.…”

“…Similar to other artificial feeding systems, the use of engineered biocompatible constructs provides an ethical alternative to methods relying on live animals or human volunteers [ Table 1 ]. The benefits include the capacity to emulate the native feeding environment of vectors within an adjustable framework [ 18 ]. In contrast to other artificial feeding systems, engineered biocompatible constructs replicate the mechanical and physical attributes of human skin, offering a more precise simulation of the innate feeding mechanism [ 162 ].…”

“…While vertebrate animals offers several advantages, such as providing a natural physiological environment for the arthropods and offering insights into host–pathogen interactions [ 13 , 14 ], ethical and practical concerns exist [ 8 , 14 , 15 , 16 , 17 ]. Alternative methods including artificial feeders have emerged to address some of these limitations and provide a more controlled approach [ 18 , 19 , 20 , 21 , 22 ]. Artificial feeding systems incorporate advanced tailored membranes, capillary feeding mechanisms, and engineered biocompatible constructs to enhance experimental accuracy and support arthropod colonies in laboratory settings [ 23 ].…”