약물처리된 심장세포의 세포 수축력 측정을 위한 병렬 폴리머 캔틸레버 제작
Fabrication of a Parallel Polymer Cantilever to Measure the Contractile Force of Drug-treated Cardiac Cells
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Thus far, several in vivo biosensing platforms have been proposed to measure the mechanical contractility of cultured cardiomyocytes. However, the low sensitivity and screening rate of the developed sensors severely limit their practical applications. In addition, intensive research and development in cardiovascular disease demand a high-throughput drug-screeningplatform based on biomimetic engineering. To overcome the drawbacks of the current state-of-the-art methods, we propose ahigh-throughput drug-screening platform based on 16 functional high-sensitivity well plates. The proposed system simulates thephysiological accuracy of the heart function in an in vitro environment. We fabricated 64 cantilevers using highly flexible andoptically transparent silicone rubber and placed in 16 independent wells. Nanogrooves were imprinted on the surface of the cantileverto promote cell alignment and maturation. The adverse effects of the cardiovascular drugs on the cultured cardiomyocyteswere systematically investigated. The 64 cantilevers demonstrated a highly reliable and reproducible mechanicalcontractility of the drug-treated cardiomyocytes. Real-time high-throughput screening and simultaneous evaluation of the cardiomyocytemechanical contractility under multiple drugs verified that the proposed system could be used as an efficient drugtoxicitytest platform.
Abstract
Thus far, several in vivo biosensing platforms have been proposed to measure the mechanical contractility of cultured cardiomyocytes. However, the low sensitivity and screening rate of the developed sensors severely limit their practical applications. In addition, intensive research and development in cardiovascular disease demand a high-throughput drug-screeningplatform based on biomimetic engineering. To overcome the drawbacks of the current state-of-the-art methods, we propose ahigh-throughput drug-screening platform based on 16 functional high-sensitivity well plates. The proposed system simulates thephysiological accuracy of the heart function in an in vitro environment. We fabricated 64 cantilevers using highly flexible andoptically transparent silicone rubber and placed in 16 independent wells. Nanogrooves were imprinted on the surface of the cantileverto promote cell alignment and maturation. The adverse effects of the cardiovascular drugs on the cultured cardiomyocyteswere systematically investigated. The 64 cantilevers demonstrated a highly reliable and reproducible mechanicalcontractility of the drug-treated cardiomyocytes. Real-time high-throughput screening and simultaneous evaluation of the cardiomyocytemechanical contractility under multiple drugs verified that the proposed system could be used as an efficient drugtoxicitytest platform.
참고문헌 (9)
- J. G. Jacot, "Cardiac myocyte force development during differentiation and maturation", Ann. N. Y. Acad. Sci, 1188, pp.121~127 (2010)
- K. S. Bielawski, "Real-time force and frequency analysis of engineered human heart tissue derived from induced pluripotent stem cells using magnetic sensing", Tissue Eng., Part C, 22(10), pp.932~940 (2016)
- I. Mannhardt, "Piezo?bending actuators for isometric or auxotonic contraction analysis of engineered heart tissue", J. Tissue Eng. Regener. Med, 13(1), pp.3~11 (2019)
- J. L. Tan, "Cells lying on a bed of microneedles : An approach to isolate mechanical force", Proc. Natl. Acad. Sci, 100(4), pp.1484~1489 (2003)
- R. E. Taylor, "Sacrificial layer technique for axial force post assay of immature cardiomyocytes", Biomed. Microdevices, 15(1), pp.171~181 (2013)
- J. You, "Cardiomyocyte sensor responsive to changes in physical and chemical environments", J. Biomech, 47(2), pp.400~409 (2014)
- J. Y. Kim, "Surfacepatterned SU-8 cantilever arrays for preliminary screening of cardiac toxicity", Biosens. Bioelectron, 80, pp.456~462 (2016)
- D. -S. Kim, "Piezoresistive sensor-integrated PDMS cantilever : A new class of device for measuring the druginduced changes in the mechanical activity of cardiomyocytes", Sens. Actuators, B, 240, pp.566~572 (2017)
- T. Kim, "Polyimide encapsulation of spider-inspired crack-based sensors for durability improvement", Appl. Sci., 8(3), pp.367(1)~367(8) (2018)