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Abstract 10751: Pericardial Injection of Micronized Matrix Biomaterial Improves Post-Infarct Cardiac Function and Modulates Fibroblast Activity to Enhance Repair

2021· article· en· W3216391023 on OpenAlexaff
Vishnu Vasanthan, Darrell D. Belke, Guoqi Teng, Ali Fatehi Hassanabad, Jameson A. Dundas, Jeannine Turnbull, Justin Deniset, Paul W.M. Fedak

Bibliographic record

VenueCirculation · 2021
Typearticle
Languageen
FieldMedicine
TopicTissue Engineering and Regenerative Medicine
Canadian institutionsFoothills Medical CentreLibin Cardiovascular Institute of Alberta
Fundersnot available
KeywordsMedicineExtracellular matrixCardiac fibrosisFibroblastFibrosisContractilityPathologyInternal medicineCell biologyIn vitroChemistry

Abstract

fetched live from OpenAlex

Introduction: Injection of micronized biomaterials into the pericardial space leverages bioinductive properties to enhance post-infarct cardiac repair. This less invasive, potentially bedside, approach enables early intervention. Micronized porcine small intestinal submucosal extracellular matrix (SIS-ECM) contains fibroblast growth factor 2 (FGF2) which reduce fibrosis and increase vasculogenesis. Hypothesis: Pericardial delivery of micronized SIS-ECM improves post-infarct cardiac function. It promotes a proangiogenic and antifibrotic fibroblast phenotype. Methods: Mice received coronary ligation (infarct) through an undisrupted pericardium followed by pericardial delivery of micronized SIS-ECM or saline control. Pressure-volume loops were at 28 days. Myocardial isolectin stain assessed small vessel density on confocal microscopy. Mouse 3T3 cell line fibroblasts in 3D collagen matrices were exposed to biomaterial-conditioned media or media control. Multiplex analyzed paracrine activity. Collagen gel contraction and MMP2 production assessed profibrotic phenotype. FGF2 inhibitor elucidated mechanism. Results: Mice receiving micronized SIS-ECM had lower ventricular stiffness (0.23±0.03 vs 0.39±0.05 mmHg/uL; p=0.01), higher ejection fraction (34.7±2.5 vs 26.9±2.8%; p<0.05) and higher stroke work (1510±138 vs 1066±152 μL/mmHg; p=0.04). The SIS-ECM group had higher normalized border zone isolectin mean fluorescence (0.82±0.04 vs 0.58±0.06; p=0.01). Micronized SIS-ECM attenuated collagen gel contraction (26±6 vs 56±5%; p=0.01) and MMP2 release (66±2 vs 83±3 ng/mL; p<0.01). Micronized SIS-ECM increased fibroblast VEGF production (904±79 vs 628±25; pg/mL). FGF2 inhibitor negated biomaterial effects, increasing gel contraction (27.3±5.3 vs 11.0±0.5%; p=0.04; inhibitor vs no inhibitor) and MMP-2 release (141±8 vs 100±6 ng/mL; p=0.02). Conclusions: Pericardial injection of micronized SIS-ECM attenuates profibrotic fibroblast activity, increases release of angiogenic VEGF protein, increases vasculogenesis on isolectin staining, and preserves post-infarct cardiac function. This less invasive strategy facilitates early intervention to attenuate maladaptive post-infarct structural remodeling.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.643
Threshold uncertainty score0.497

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.257
Teacher spread0.251 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations2
Published2021
Admission routes1
Has abstractyes

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