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

• Published in: Insects (Basel, Switzerland) Switzerland), 2023-06, Vol.14 (6), p.514
• Main Authors: Seavey, Corey E, Doshi, Mona, Panarello, Andrew P, Felice, Michael A, Dickerson, Andrew K, Jewett, Mollie W, Willenberg, Bradley J
• Format: Article
• Language: English
• Subjects: Aedes aegypti; Alginates; Alginic acid; Arthropoda; Arthropods; Beds (process engineering); Biological research; Biology; Biology, Experimental; Biomaterials; Biomedical materials; Bites and stings; Biting; Blood; Blood meals; Blood vessels; blood-feeding; Capgel; Cell culture; Control; Culicidae; Dengue fever; Disease transmission; Endothelial cells; Females; Fibroblasts; Food; Genetic aspects; Health risks; Human tissues; Infectious diseases; Innovations; Insect bites; Microvasculature; Molecular biology; Mosquitoes; Pathogens; Penicillin; Saliva; Scaffolds; Skin; Three dimensional models; Tissue culture; Tissue engineering; Tropical diseases; Umbilical vein; Vector-borne diseases; Vectors; Zika virus
• ISSN: 2075-4450; 2075-4450
• DOI: 10.3390/insects14060514

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 ( .) 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.