ArticleOsteoarthritis and cartilage2014
A high-throughput model of post-traumatic osteoarthritis using engineered cartilage tissue analogs.
Article in Osteoarthritis and cartilage, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Identifying small molecules for protecting chondrocyte function and matrix integrity after controlled compressive injury.Osteoarthritis and cartilage open · 2022Article
- Concentration Threshold for Membrane Protection by PEO-PPO Block Copolymers with Variable Molecular Architectures.ACS applied polymer materials · 2022Article
- Two-Dimensional and Three-Dimensional Cartilage Model Platforms for Drug Evaluation and High-Throughput Screening Assays.Tissue engineering. Part B, Reviews · 2022Review
- A High-Throughput Mechanical Activator for Cartilage Engineering Enables Rapid Screening of in vitro Response of Tissue Models to Physiological and Supra-Physiological Loads.Cells, tissues, organs · 2022Article
- General Caspase Inhibition in Primary Chondrogenic Cultures Impacts Their Transcription Profile Including Osteoarthritis-Related Factors.Cartilage · 2021Article
- Mechanobiological model for simulation of injured cartilage degradation via pro-inflammatory cytokines and mechanical stimulus.PLoS computational biology · 2020Article
- Scaffoldless tissue-engineered cartilage for studying transforming growth factor beta-mediated cartilage formation.Biotechnology progress · 2020Article
- Obesity alters the in vivo mechanical response and biochemical properties of cartilage as measured by MRI.Arthritis research & therapy · 2018Article
- PEO-PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture.Biomacromolecules · 2017Article
- Three-Dimensional Biomechanical Analysis of Rearfoot and Forefoot Running.Orthopaedic journal of sports medicine · 2017Article
- Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis.Scientific reports · 2016Article
- Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation.RMD open · 2016Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveA number of in vitro models of post-traumatic osteoarthritis (PTOA) have been developed to study the effect of mechanical overload on the processes that regulate cartilage degeneration. While such frameworks are critical for the identification therapeutic targets, existing technologies are limited in their throughput capacity. Here, we validate a test platform for high-throughput mechanical injury incorporating engineered cartilage.
methodWe utilized a high-throughput mechanical testing platform to apply injurious compression to engineered cartilage and determined their strain and strain rate dependent responses to injury. Next, we validated this response by applying the same injury conditions to cartilage explants. Finally, we conducted a pilot screen of putative PTOA therapeutic compounds.
resultsEngineered cartilage response to injury was strain dependent, with a 2-fold increase in glycosaminoglycan (GAG) loss at 75% compared to 50% strain. Extensive cell death was observed adjacent to fissures, with membrane rupture corroborated by marked increases in lactate dehydrogenase (LDH) release. Testing of established PTOA therapeutics showed that pan-caspase inhibitor [Z-VAD-FMK (ZVF)] was effective at reducing cell death, while the amphiphilic polymer [Poloxamer 188 (P188)] and the free-radical scavenger [N-Acetyl-L-cysteine (NAC)] reduced GAG loss as compared to injury alone.
conclusionsThe injury response in this engineered cartilage model replicated key features of the response of cartilage explants, validating this system for application of physiologically relevant injurious compression. This study establishes a novel tool for the discovery of mechanisms governing cartilage injury, as well as a screening platform for the identification of new molecules for the treatment of PTOA.
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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.