Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations

Vector-borne diseases transmitted through the bites of hematophagous arthropods, such as mosquitoes, continue to be a significant threat to human health globally. Transmission of disease by biting arthropod vectors includes interactions between (1) saliva expectorated by a vector during blood meal a...

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Main Authors: Corey E. Seavey, Mona Doshi, Andrew P. Panarello, Michael A. Felice, Andrew K. Dickerson, Mollie W. Jewett, Bradley J. Willenberg
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Insects
Subjects:
Online Access:https://www.mdpi.com/2075-4450/14/6/514
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author Corey E. Seavey
Mona Doshi
Andrew P. Panarello
Michael A. Felice
Andrew K. Dickerson
Mollie W. Jewett
Bradley J. Willenberg
author_facet Corey E. Seavey
Mona Doshi
Andrew P. Panarello
Michael A. Felice
Andrew K. Dickerson
Mollie W. Jewett
Bradley J. Willenberg
author_sort Corey E. Seavey
collection DOAJ
description Vector-borne diseases transmitted through the bites of hematophagous arthropods, such as mosquitoes, continue to be a significant threat to human health globally. Transmission of disease by biting arthropod vectors includes interactions between (1) saliva expectorated by a vector during blood meal acquisition from a human host, (2) the transmitted vector-borne pathogens, and (3) host cells present at the skin bite site. Currently, the investigation of bite-site biology is challenged by the lack of model 3D human skin tissues for in vitro analyses. To help fill this gap, we have used a tissue engineering approach to develop new stylized human dermal microvascular bed tissue approximates—complete with warm blood—built with 3D capillary alginate gel (Capgel) biomaterial scaffolds. These engineered tissues, termed a Biologic Interfacial Tissue-Engineered System (BITES), were cellularized with either human dermal fibroblasts (HDFs) or human umbilical vein endothelial cells (HUVECs). Both cell types formed tubular microvessel-like tissue structures of oriented cells (82% and 54% for HDFs and HUVECs, respectively) lining the unique Capgel parallel capillary microstructures. Female <i>Aedes</i> (<i>Ae</i>.) <i>aegypti</i> mosquitoes, a prototypic hematophagous biting vector arthropod, swarmed, bit, and probed blood-loaded HDF BITES microvessel bed tissues that were warmed (34–37 °C), acquiring blood meals in 151 ± 46 s on average, with some ingesting ≳4 µL or more of blood. Further, these tissue-engineered constructs could be cultured for at least three (3) days following blood meal acquisitions. Altogether, these studies serve as a powerful proof-of-concept demonstration of the innovative BITES platform and indicate its potential for the future investigation of arthropod bite-site cellular and molecular biology.
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spelling doaj.art-0e240fab74aa4943b123688a59e0dd252023-11-18T10:55:52ZengMDPI AGInsects2075-44502023-06-0114651410.3390/insects14060514Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology InvestigationsCorey E. Seavey0Mona Doshi1Andrew P. Panarello2Michael A. Felice3Andrew K. Dickerson4Mollie W. Jewett5Bradley J. Willenberg6Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USADepartment of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USADepartment of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USADepartment of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USADepartment of Mechanical, Aerospace, and Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USADivision of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL 32827, USADepartment of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USAVector-borne diseases transmitted through the bites of hematophagous arthropods, such as mosquitoes, continue to be a significant threat to human health globally. Transmission of disease by biting arthropod vectors includes interactions between (1) saliva expectorated by a vector during blood meal acquisition from a human host, (2) the transmitted vector-borne pathogens, and (3) host cells present at the skin bite site. Currently, the investigation of bite-site biology is challenged by the lack of model 3D human skin tissues for in vitro analyses. To help fill this gap, we have used a tissue engineering approach to develop new stylized human dermal microvascular bed tissue approximates—complete with warm blood—built with 3D capillary alginate gel (Capgel) biomaterial scaffolds. These engineered tissues, termed a Biologic Interfacial Tissue-Engineered System (BITES), were cellularized with either human dermal fibroblasts (HDFs) or human umbilical vein endothelial cells (HUVECs). Both cell types formed tubular microvessel-like tissue structures of oriented cells (82% and 54% for HDFs and HUVECs, respectively) lining the unique Capgel parallel capillary microstructures. Female <i>Aedes</i> (<i>Ae</i>.) <i>aegypti</i> mosquitoes, a prototypic hematophagous biting vector arthropod, swarmed, bit, and probed blood-loaded HDF BITES microvessel bed tissues that were warmed (34–37 °C), acquiring blood meals in 151 ± 46 s on average, with some ingesting ≳4 µL or more of blood. Further, these tissue-engineered constructs could be cultured for at least three (3) days following blood meal acquisitions. Altogether, these studies serve as a powerful proof-of-concept demonstration of the innovative BITES platform and indicate its potential for the future investigation of arthropod bite-site cellular and molecular biology.https://www.mdpi.com/2075-4450/14/6/514Capgelmosquitoes<i>Aedes aegypti</i>arthropodsblood-feeding
spellingShingle Corey E. Seavey
Mona Doshi
Andrew P. Panarello
Michael A. Felice
Andrew K. Dickerson
Mollie W. Jewett
Bradley J. Willenberg
Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations
Insects
Capgel
mosquitoes
<i>Aedes aegypti</i>
arthropods
blood-feeding
title Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations
title_full Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations
title_fullStr Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations
title_full_unstemmed Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations
title_short Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations
title_sort engineered human tissue as a new platform for mosquito bite site biology investigations
topic Capgel
mosquitoes
<i>Aedes aegypti</i>
arthropods
blood-feeding
url https://www.mdpi.com/2075-4450/14/6/514
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