{"doi":"10.1002/adhm.202001941","title":"Oxidation‐Responsive, Tunable Growth Factor Delivery from Polyelectrolyte‐Coated Implants","abstract":"Polyelectrolyte multilayer (PEM) coatings, constructed on the surfaces of tissue engineering scaffolds using layer-by-layer assembly (LbL), promote sustained release of therapeutic molecules and have enabled regeneration of large-scale, pre-clinical bone defects. However, these systems primarily rely on non-specific hydrolysis of PEM components to foster drug release, and their pre-determined drug delivery schedules potentially limit future translation into innately heterogeneous patient populations. To trigger therapeutic delivery directly in response to local environmental stimuli, an LbL-compatible polycation solely degraded by cell-generated reactive oxygen species (ROS) was synthesized. These thioketal-based polymers were selectively cleaved by physiologic doses of ROS, stably incorporated into PEM films alongside growth factors, and facilitated tunable release of therapeutic bone morphogenetic protein-2 (BMP-2) upon oxidation. These coatings' sensitivity to oxidation was also dependent on the polyanions used in film construction, providing a simple method for enhancing ROS-mediated protein delivery in vitro. Correspondingly, when implanted in critically-sized rat calvarial defects, the most sensitive ROS-responsive coatings generated a 50% increase in bone regeneration compared with less sensitive formulations and demonstrated a nearly threefold extension in BMP-2 delivery half-life over conventional hydrolytically-sensitive coatings. These combined results highlight the potential of environmentally-responsive PEM coatings as tunable drug delivery systems for regenerative medicine.","journal":"Advanced Healthcare Materials","year":2021,"id":168451,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9427,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":698605,"name":"MayLin T. Howard","orcid":null,"position":1,"is_corresponding":false},{"id":698606,"name":"Sheryl Wang","orcid":null,"position":2,"is_corresponding":false},{"id":697815,"name":"Adam G. Berger","orcid":"0000-0002-3813-8684","position":3,"is_corresponding":false},{"id":263335,"name":"Paula T. Hammond","orcid":"0000-0002-9835-192X","position":4,"is_corresponding":false},{"id":294526,"name":"John R. Martin","orcid":"0000-0003-1681-3818","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-18T23:46:06.853307Z","pmid":"33738985","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":[]}