Development of a Human Respiratory Mucosa-on-a-chip using Decellularized Extracellular Matrix
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Original Article
Development of a Human Respiratory Mucosa-on-a-chip using Decellularized Extracellular Matrix Mi Hyun Lim1,2,†, Min Jae Lim1,2,†, Won-Soo Yun3,4, Songwan Jin3,4, Donghyun Lee3,4, Do Hyun Kim 1,* & Sung Won Kim 1,* Received: 26 April, 2020 / Accepted: 9 Jun, 2020 / Published online: 27 August, 2020 ⒸThe Korean BioChip Society and Springer 2020
Abstract The airway mucosa is the first point of exposure to all inhalant materials. It is possible to produce microenvironments functionally similar to airway by using different types of extracellular matrices around mucosal cells, such as an extracellular matrix decellularized from trachea. In this study, we introduced a novel human respiratory mucosa-on-achip model that uses decellularized tracheal extracellular matrix to assess functional similarities. We also evaluated the effects of respiratory toxicant based on changes in cell viability, tight junction function, oxidative stress, expression of cell adhesion proteins in the vascular network, mucous secretion, and inflammatory cytokine secretion after treatment. This novel human respiratory mucosa-on-a-chip model is expected to be useful for assessing respiratory mucosa reactions to external bacteria or viruses and inhaled drugs. Keywords: Extracellular matrix, Respiratory system, Humans 1 Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea 2 Institute of Clinical Medicine Research, College of Medicine, The Catholic University of Korea, 222, Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea 3 T&R Biofab. Co. Ltd. 242 Pangyo-ro, Seongnam-si, Gyeonggi-do 13487, Republic of Korea 4 Department of Mechanical Engineering Korea Polytechnic University 237 Sangidaehak-ro, Siheung-si, Gyeonggi-do 15073 Republic of Korea † These authors contributed equally. *Correspondence and requests for materials should be addressed to D.H. Kim ( [email protected]) and S.W. Kim ( [email protected])
Introduction The respiratory mucosa is the first point of exposure to all inhalant materials (e.g., allergens, inhalant microorganisms, viruses, and air pollutants); thus, it serves to protect lower airways1. Furthermore, it functions as a physical and immune barrier against dangerous environmental factors2. Research regarding the airway epithelium is useful to reveal the pathologies of many respiratory diseases, including various infectious, genetic, and inflammatory diseases. Damaged nasal epithelial and sub-epithelial systems are involved in the induction of nasal diseases, such as nasal polyps, sinusitis, or cystic fibrosis3-5. Furthermore, mucociliary clearance is an intrinsic defense mechanism by which the airway protects against external stimulants. Several customized microfluidic airway-on-a-chip approaches have been developed to provide air– liquid interface (ALI) culture conditions6-9. To the best of our knowledge, there remain few models that systematically assess functio
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