Location: Research Programs
Project Number: 3022-32000-018-012-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 1, 2022
End Date: Sep 1, 2025
The hydrogel skin system mimics (HSS) a vascularized skin model and could be used to investigate host-virus-vector interactions. This in vitro system could expedite research in the areas of entomology and immunology towards evaluation of therapeutic options (vaccines and drugs), new preventive alternatives (repellents) and control strategies (transmission blocking vaccines). The objective of this study is to measure the utility of the hydrogel-based skin system in arbovirus studies including Japanese Encephalitis Virus (JEV) and West Nile Virus, both as an in vitro system and as a replacement for traditional animal studies. Objective 1: Validate the ability of the HSS to replicate the effect of viral infection in animal blood meal acquisition from skin-like environment. Objective 2: Validate the ability of the HSS to replicate in vivo virus-saliva interactions in a defined, cellularized in vitro system.
The biocompatibility of the hydrogels allows for culturing of living cells on and/or within the gel matrix. The hydrogel skin system (HSS) allows for the embedding and culture of living cells and is highly flexible and adaptable to different cell types. These studies will utilize this flexibility by embedding human and animal keratinocytes within the gel body and culturing endothelial cells within the 3D printed vasculature. Virus-infected laboratory reared mosquitoes will be allowed to feed on the cellularized HSS. The ability of the hydrogel skin system to replicate in vivo virus-vector-host interactions (e.g., virus-saliva interactions) in a defined, cellularized in vitro system will be evaluated against published data using traditional in vivo models. Taken together, these data will demonstrate the potential of the HSS to replace animal models in arboviral infection experiments.