한빛사논문
- 조회361
Jungbin Yoon1, Narendra K. Singh2,3, Jinah Jang1,4,5,a), and Dong-Woo Cho1,5,a)
1Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea
2Division of Biomaterials and Biomechanics, School of Dentistry Oregon Health and Science University (OHSU), Portland, OR 97201, USA
3Cancer Early Detection Advanced Research Center (CEDAR), OHSU-Knight Cancer Institute, Portland, OR 97201, USA
4Department of Convergence IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea
5Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea
a)Authors to whom correspondence should be addressed: Jinah Jang, Dong-Woo Cho
Abstract
Secondary hyperoxaluria (SH) is a multifactorial disorder that extends from inflamed intestinal epithelium with oxalate malabsorption to kidney stone disease; its prevalence is increasing annually. Studying complex SH has been a considerable challenge because of the lack of an in vitro multiorgan model that describes dynamic pathophysiological interactions between the native intestinal epithelium and proximal tubule (PT). An in vitro multiorgan model is developed using a multi-biofabrication technique to address this challenge; this developed microfluidic in vitro multiorgan model demonstrates the enhanced functional interconnection between the intestinal epithelium and a vascularized PT by printing compartmentalized two organs close together. This spatially organized multiorgan model with enhanced fluidic connectivity provides a tool for recapitulating the critical pathophysiological features of SH, which includes intestinal barrier disruption, calcium oxalate (CaOx) crystallization, and crystal-induced PT injuries. The biophysical properties (e.g., glucose reabsorption and tubular fluid flow behavior-dependent CaOx crystal formation) of an in vitro SH model are thoroughly analyzed by comparison with the pathophysiology of human PT. Further, the efficiency of the in vitro 3D model as a drug testing platform is validated by assessing CaOx crystal dissolution on perfusing the device with trisodium citrate and grape seed extract. With no U.S. Food and Drug Administration (FDA)-approved SH therapeutics, this optimized in vitro SH model can be actively utilized as a promising platform for discovering integrative therapeutics to reverse intestinal epithelial inflammation and recurrent kidney stone disease in a single assay.
논문정보
- Research article
- 2022년 11월 (BRIC 등록일 2023-03-06)
- 국내 연구진
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