{"doi":"10.1016/j.bioactmat.2025.03.017","title":"Synergistic effects of electrical and chemical cues with biodegradable scaffolds for large peripheral nerve defect regeneration","abstract":"Large-gap peripheral nerve injuries (PNI) are often treated with autografts, allografts, or synthetic grafts to facilitate nerve regeneration, but these options are often limited in their availability or functionality. To address these issues, we developed ionically conductive (IC) nerve guidance conduits (NGCs) of sufficient biodegradability, mechanical strength, and bioactivity to support large-gap nerve regeneration. These chitosan-based NGCs release 4-aminopyridine (4-AP) from embedded halloysite nanotubes, and the NGC's IC properties enable transcutaneous electrical stimulation (ES) without invasive electrodes. In vitro , we found scaffolds with ES+4-AP synergistically enhanced Schwann cell adhesion, proliferation, and neurotrophin secretion, significantly improving axonal growth and neurite extension. In vivo , these scaffolds in large-gap PNI boosted neurotrophin levels, myelination, nerve function, and muscle weight while promoting angiogenesis and reducing fibrosis. Upregulated Trk receptors and PI3K/Akt and MAPK pathway highlight the regenerative potential. This study advances understanding of ES-mediated regeneration and supports innovative strategies for nerve and musculoskeletal repair. • Developed ionically conductive chitosan-based nerve guidance conduits (NGCs) for large-gap PNI. • Sustained delivery of chemical agent 4-AP and electrical stimulation via NGCs to promote healing. • ES+4-AP treatment synergistically boosted Schwann cell activity & neurotrophin release in vitro . • Combined ES+4-AP treatment improved nerve healing & electrophysiology in 2 & 4 cm long nerve defects. • Upregulated Trk/PI3K/Akt and MAPK pathways underscore nerve regeneration potential.","journal":"Bioactive Materials","year":2025,"id":519286,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"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":545733,"name":"Sama Abdulmalik","orcid":"0000-0002-0834-8357","position":1,"is_corresponding":false},{"id":278275,"name":"Allen Zennifer","orcid":"0000-0002-0618-5507","position":2,"is_corresponding":false},{"id":1201232,"name":"Suranji Wijekoon","orcid":"0000-0002-7053-5268","position":3,"is_corresponding":false},{"id":1213087,"name":"Sai Sadhananth Srinivasan","orcid":"0009-0000-7888-6663","position":4,"is_corresponding":false},{"id":1387619,"name":"Ergin Coskun","orcid":"0000-0002-2108-4608","position":5,"is_corresponding":false},{"id":1388206,"name":"Yeshavanth Kumar Banasavadi Siddegowda","orcid":null,"position":6,"is_corresponding":false},{"id":480679,"name":"Xiaojun Yu","orcid":"0000-0002-3822-1760","position":7,"is_corresponding":false},{"id":250006,"name":"Sangamesh G. Kumbar","orcid":"0000-0001-7672-4783","position":8,"is_corresponding":false},{"id":463234,"name":"Rosalie Bordett","orcid":"0000-0001-9650-6062","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:18.751199Z","pmid":"40212780","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":[]}