{"doi":"10.3390/jcdd7040053","title":"A Bioengineered Neuregulin-Hydrogel Therapy Reduces Scar Size and Enhances Post-Infarct Ventricular Contractility in an Ovine Large Animal Model","abstract":"The clinical efficacy of neuregulin (NRG) in the treatment of heart failure is hindered by off-target exposure due to systemic delivery. We previously encapsulated neuregulin in a hydrogel (HG) for targeted and sustained myocardial delivery, demonstrating significant induction of cardiomyocyte proliferation and preservation of post-infarct cardiac function in a murine myocardial infarction (MI) model. Here, we performed a focused evaluation of our hydrogel-encapsulated neuregulin (NRG-HG) therapy’s potential to enhance cardiac function in an ovine large animal MI model. Adult male Dorset sheep (n = 21) underwent surgical induction of MI by coronary artery ligation. The sheep were randomized to receive an intramyocardial injection of saline, HG only, NRG only, or NRG-HG circumferentially around the infarct borderzone. Eight weeks after MI, closed-chest intracardiac pressure–volume hemodynamics were assessed, followed by heart explant for infarct size analysis. Compared to each of the control groups, NRG-HG significantly augmented left ventricular ejection fraction (p = 0.006) and contractility based on the slope of the end-systolic pressure–volume relationship (p = 0.006). NRG-HG also significantly reduced infarct scar size (p = 0.002). Overall, using a bioengineered hydrogel delivery system, a one-time dose of NRG delivered intramyocardially to the infarct borderzone at the time of MI in adult sheep significantly reduces scar size and enhances ventricular contractility at 8 weeks after MI.","journal":"Journal of Cardiovascular Development and Disease","year":2020,"id":83123,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271803,"name":"Andrew B. Goldstone","orcid":"0000-0002-2875-1290","position":1,"is_corresponding":false},{"id":351363,"name":"Hanjay Wang","orcid":"0000-0002-2367-5591","position":2,"is_corresponding":false},{"id":429247,"name":"Brendan P. Purcell","orcid":null,"position":3,"is_corresponding":false},{"id":428146,"name":"Yasuhiro Shudo","orcid":"0000-0002-4545-1273","position":4,"is_corresponding":false},{"id":428147,"name":"John W. MacArthur","orcid":"0000-0003-3385-4216","position":5,"is_corresponding":false},{"id":351372,"name":"Amanda N. Steele","orcid":"0000-0002-9872-5442","position":6,"is_corresponding":false},{"id":351364,"name":"Michael J. Paulsen","orcid":"0000-0003-1730-0678","position":7,"is_corresponding":false},{"id":429248,"name":"Bryan B. Edwards","orcid":null,"position":8,"is_corresponding":false},{"id":429249,"name":"Chiaka N Aribeana","orcid":null,"position":9,"is_corresponding":false},{"id":428148,"name":"Nicholas C. Cheung","orcid":"0000-0003-2711-019X","position":10,"is_corresponding":false},{"id":235269,"name":"Jason A. Burdick","orcid":"0000-0002-2006-332X","position":11,"is_corresponding":false},{"id":271806,"name":"Y. Joseph Woo","orcid":"0000-0002-2506-492X","position":12,"is_corresponding":false},{"id":428145,"name":"Jeffrey Е. Cohen","orcid":"0000-0002-3002-018X","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T21:54:09.383533Z","pmid":"33212844","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}