Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6485636 | Biomaterials | 2015 | 10 Pages |
Abstract
A hallmark of mature mammalian ventricular myocardium is a positive force-frequency relationship (FFR). Despite evidence of organotypic structural and molecular maturation, a positive FFR has not been observed in mammalian tissue engineered heart muscle. We hypothesized that concurrent mechanical and electrical stimulation at frequencies matching physiological heart rate will result in functional maturation. We investigated the role of biomimetic mechanical and electrical stimulation in functional maturation in engineered heart muscle (EHM). Following tissue consolidation, EHM were subjected to electrical field stimulation at 0, 2, 4, or 6Â Hz for 5 days, while strained on flexible poles to facilitate auxotonic contractions. EHM stimulated at 2 and 4Â Hz displayed a similarly enhanced inotropic reserve, but a clearly diverging FFR. The positive FFR in 4Â Hz stimulated EHM was associated with reduced calcium sensitivity, frequency-dependent acceleration of relaxation, and enhanced post-rest potentiation. This was paralleled on the cellular level with improved calcium storage and release capacity of the sarcoplasmic reticulum and enhanced T-tubulation. We conclude that electro-mechanical stimulation at a physiological frequency supports functional maturation in mammalian EHM. The observed positive FFR in EHM has important implications for the applicability of EHM in cardiovascular research.
Keywords
Post-rest potentiationSERCA2aLTCCWGAEHMPBSPrPAAVFFRDMSSarco/endoplasmic reticulumRyR2Ca2+FOCATPaseMaturationBiophysical propertiesCalcium handlingforce-frequency relationshipSarcoplasmic reticulumHeartphosphate buffered solutionTissue engineeringMyocardiumForce of contractioncalsequestrin 2L-type calcium channelWheat germ agglutininRyanodine receptor 2
Related Topics
Physical Sciences and Engineering
Chemical Engineering
Bioengineering
Authors
Amandine F.G. Godier-Furnémont, Malte Tiburcy, Eva Wagner, Matthias Dewenter, Simon Lämmle, Ali El-Armouche, Stephan E. Lehnart, Gordana Vunjak-Novakovic, Wolfram-Hubertus Zimmermann,