{"doi":"10.1016/j.bioadv.2025.214424","title":"Injection of vocal fold lamina propria-derived hydrogels modulates fibrosis in injured vocal folds","abstract":"Vocal fold (VF) fibrosis, often resulting from phonosurgery, radiation, or trauma, causes irreversible voice dysfunction due to excessive ECM deposition and increased tissue stiffness. No FDA-approved treatments for VF fibrosis exist, highlighting the need for novel antifibrotic therapies. TGF-β1 contributes to fibroblast-to-myofibroblast activation, leading to increased ACTA2 expression and collagen production via SMAD3, YAP1, and integrin signaling pathways. Leveraging the principle that local cells respond to tissue-specific signals, our ECM hydrogel, derived from decellularized vocal fold lamina propria (VFLP-ECM), reduced ACTA2 expression in TGF-β1-stimulated VF fibroblasts, showcasing antifibrotic potential. This study evaluates the therapeutic potential of VFLP-ECM hydrogel in a rabbit VF injury model. VFLP-ECM hydrogel or bovine type I collagen injections were administered 7 days post-injury and evaluated on day 28. We compared two VFLP-ECM formulations: a manual process (VFLP (man)) and an accelerated automated method (VFLP (au)). VFLP (man) modulated fibrosis-associated gene expressions more effectively than controls. Proteomics identified 229 proteins uniquely preserved in VFLP (man), including vitronectin, crucial in TGF-β1 signaling and ECM remodeling. Transcriptomic analysis suggests downregulation of fibrotic markers and inhibition of SMAD3, YAP1, and MRTFA, alongside upregulation of SMAD7, an inhibitor of TGF-β signaling. Notably, VFLP (man) treatment recovered stiffness comparable to uninjured controls (1.84 vs. 1.94 mN), whereas collagen-treated tissues remained stiff (2.7 mN), similar to the injury group (2.6 mN), indicating incomplete mechanical recovery. These in vivo data show that manually decellularized VFLP-ECM hydrogel attenuates fibrosis by disrupting key biochemical and mechanical cues driving myofibroblast activation. • Tissue-specific VFLP-ECM hydrogel restores vocal fold mechanics in vivo 28 days after injury. • VFLP-ECM hydrogel shows improved vocal fold repair compared to type I collagen. • Proteomic analysis indicates that matrisome proteins like vitronectin may drive the in vivo response. • Transcriptomic data reveal that ECM hydrogel inhibits fibrosis through non-canonical mechanisms.","journal":"Biomaterials Advances","year":2025,"id":517580,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":804103,"name":"Ethan Smith","orcid":"0000-0001-8897-2143","position":1,"is_corresponding":false},{"id":1383892,"name":"Ziyu Wang","orcid":"0000-0002-1452-5903","position":2,"is_corresponding":false},{"id":1384576,"name":"Maria Del C Ramos-Alamo","orcid":null,"position":3,"is_corresponding":false},{"id":395054,"name":"Leonard B. Collins","orcid":"0000-0002-7734-9708","position":4,"is_corresponding":false},{"id":1384577,"name":"Nour Awad","orcid":null,"position":5,"is_corresponding":false},{"id":1384578,"name":"Denzel Ryan D. Cruz","orcid":null,"position":6,"is_corresponding":false},{"id":821478,"name":"Tammy Tollison","orcid":"0000-0002-7193-8456","position":7,"is_corresponding":false},{"id":784150,"name":"Ian Huntress","orcid":null,"position":8,"is_corresponding":false},{"id":894169,"name":"Gary J. Gartling","orcid":"0000-0002-5362-0866","position":9,"is_corresponding":false},{"id":367687,"name":"Ryosuke Nakamura","orcid":"0000-0003-0061-2114","position":10,"is_corresponding":false},{"id":968703,"name":"Gregory R. Dion","orcid":"0000-0003-4389-3104","position":11,"is_corresponding":false},{"id":228260,"name":"Xinxia Peng","orcid":"0000-0002-0117-3582","position":12,"is_corresponding":false},{"id":367690,"name":"Ryan C. Branski","orcid":"0000-0003-1190-9036","position":13,"is_corresponding":false},{"id":245145,"name":"Donald O. Freytes","orcid":"0000-0003-4636-5809","position":14,"is_corresponding":false},{"id":363782,"name":"Camilo Mora‐Navarro","orcid":"0000-0001-6863-8068","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:59.410472Z","pmid":"40763684","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":[]}