Challenges of aortic valve tissue culture – maintenance of viability and extracellular matrix in the pulsatile dynamic microphysiological system

Journal of Biological Engineering

Research

Klaus Matschke¹  Maximilian Winkelkotte¹  Anna Scheer¹  Emmely Voigt¹  Anett Jannasch¹  Claudia Dittfeld¹  Sems-Malte Tugtekin¹  Florian Schmieder²  Stephan Behrens²  Frank Sonntag² 

[1] Department of Cardiac Surgery, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Heart Centre Dresden, Fetscherstr. 76, 01307, Dresden, Germany;Fraunhofer Institute for Material and Beam Technology IWS, Dresden, Germany;

关键词: Calcific aortic valve disease;    Tissue culture;    Microphysiological system;    Viability;    ECM remodelling;   

DOI  :  10.1186/s13036-023-00377-1

 received in 2023-05-15, accepted in 2023-09-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCalcific aortic valve disease (CAVD) causes an increasing health burden in the 21st century due to aging population. The complex pathophysiology remains to be understood to develop novel prevention and treatment strategies. Microphysiological systems (MPSs), also known as organ-on-chip or lab-on-a-chip systems, proved promising in bridging in vitro and in vivo approaches by applying integer AV tissue and modelling biomechanical microenvironment. This study introduces a novel MPS comprising different micropumps in conjunction with a tissue-incubation-chamber (TIC) for long-term porcine and human AV incubation (pAV, hAV).ResultsTissue cultures in two different MPS setups were compared and validated by a bimodal viability analysis and extracellular matrix transformation assessment. The MPS-TIC conjunction proved applicable for incubation periods of 14–26 days. An increased metabolic rate was detected for pulsatile dynamic MPS culture compared to static condition indicated by increased LDH intensity. ECM changes such as an increase of collagen fibre content in line with tissue contraction and mass reduction, also observed in early CAVD, were detected in MPS-TIC culture, as well as an increase of collagen fibre content. Glycosaminoglycans remained stable, no significant alterations of α-SMA or CD31 epitopes and no accumulation of calciumhydroxyapatite were observed after 14 days of incubation.ConclusionsThe presented ex vivo MPS allows long-term AV tissue incubation and will be adopted for future investigation of CAVD pathophysiology, also implementing human tissues. The bimodal viability assessment and ECM analyses approve reliability of ex vivo CAVD investigation and comparability of parallel tissue segments with different treatment strategies regarding the AV (patho)physiology.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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