ArticleBiomaterials2015
Physiologic force-frequency response in engineered heart muscle by electromechanical stimulation.
Article in Biomaterials, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 3 syntheses or guidelines pooled it, 154 citations in OpenAlex.
- Guidelines for assessing maternal cardiovascular physiology during pregnancy and postpartum.American journal of physiology. Heart and circulatory physiology · 2024Guideline
- Towards chamber specific heart-on-a-chip for drug testing applications.Advanced drug delivery reviews · 2020Pooled it
- ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure.Cardiovascular research · 2019Guideline
- High and intermittent hydrostatic pressure promotes maturation of engineered cardiac tissues derived from human pluripotent stem cells.Stem cell reports · 2026Article
- The roles of the microtubule cytoskeletal network in cardiac mechanobiology.Journal of cell science · 2026Review
- In vitro approaches to mimic cardiac mechanical load dynamics for enhancing maturation and disease modelling.Cardiovascular research · 2025Review
- Novel Electroactive Therapeutic Platforms for Cardiac Arrhythmia Management.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Cardiomyocytes in Hypoxia: Cellular Responses and Implications for Cell-Based Cardiac Regenerative Therapies.Bioengineering (Basel, Switzerland) · 2025Review
- From function to structure: how myofibrillogenesis influences the transverse-axial tubular system development and its peculiarities.Frontiers in physiology · 2025Review
- The development, use, and challenges of electromechanical tissue stimulation systems.Artificial organs · 2024Review
- Analysis of the role of perfusion, mechanical, and electrical stimulation in bioreactors for cardiac tissue engineering.Bioprocess and biosystems engineering · 2024Review
- Engineered heart tissue: Design considerations and the state of the art.Biophysics reviews · 2024Review
- Advances in cardiac tissue engineering and heart-on-a-chip.Journal of biomedical materials research. Part A · 2024Review
- Geometry and length control of 3D engineered heart tissues using direct laser writing.Lab on a chip · 2024Article
- Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment.iScience · 2024Article
- FRESH™ 3D bioprinted cardiac tissue, a bioengineered platform forAPL bioengineering · 2023Article
- Induced pluripotent stem cell-derived cardiomyocytes-more show than substance?Biophysical reviews · 2023Review
- Continuous contractile force and electrical signal recordings of 3D cardiac tissue utilizing conductive hydrogel pillars on a chip.Materials today. Bio · 2023Article
- Membrane Remodeling of Human-Engineered Cardiac Tissue by Chronic Electric Stimulation.ACS biomaterials science & engineering · 2023Article
- Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering.Circulation research · 2023Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
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 6 Hz for 5 days, while strained on flexible poles to facilitate auxotonic contractions. EHM stimulated at 2 and 4 Hz displayed a similarly enhanced inotropic reserve, but a clearly diverging FFR. The positive FFR in 4 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.