{"doi":"10.1002/adhm.202502475","title":"Synthetic Hydrogels Incorporating Hydrolytic/Nonhydrolytic Macromer Ratios Exhibit Improved Tunability of In Vivo Degradation and Immune Responses","abstract":"Proteolytically degradable hydrogels are widely used as delivery carriers in regenerative medicine. However, the in vivo degradation rate of these materials is difficult to control because of site-specific enzymatic activity, implant design, and disease state, impairing tissue regeneration. Hydrogels with crosslinks that degrade hydrolytically offer an alternate route to tune in vivo degradation profile. In this study, a synthetic 4-arm maleimide-terminated poly(ethylene glycol) (PEG-4MAL) hydrogel system that combines hydrolytic ester-linked PEG-4MAL (PEG-4eMAL) macromer with nondegradable amide-linked PEG-4MAL (PEG-4aMAL) macromer in various stoichiometric ratios to tune the degradability rate is engineered. The macromers are crosslinked with dithiothreitol (DTT) via thiol-maleimide click reaction. Rheological analysis shows that a family of PEG-4eMAL/PEG-4aMAL hydrogels has equivalent mechanical properties, but increasing the PEG-4eMAL content increases the rate of degradation in vitro and in vivo. PEG-4eMAL/PEG-4aMAL hydrogels support high viability of encapsulated human cells. Notably, the ratio of PEG-4eMAL/PEG-4aMAL modulates local immune cell recruitment when implanted in the subcutaneous space. These results establish the use of PEG-4eMAL/PEG-4aMAL hydrogels as a hydrolytically degradable platform to tune in vivo degradation and immune responses.","journal":"Advanced Healthcare Materials","year":2025,"id":520160,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"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":885105,"name":"Sophia Kioulaphides","orcid":null,"position":1,"is_corresponding":false},{"id":245029,"name":"Karen E. Martin","orcid":"0000-0003-0261-6709","position":2,"is_corresponding":false},{"id":865648,"name":"Angelica L. Torres","orcid":"0000-0003-2417-0138","position":3,"is_corresponding":false},{"id":296587,"name":"Graham F. Barber","orcid":null,"position":4,"is_corresponding":false},{"id":910473,"name":"Stephen W. Linderman","orcid":"0000-0002-1797-5870","position":5,"is_corresponding":false},{"id":495493,"name":"Rebecca Schneider","orcid":"0000-0001-7346-6723","position":6,"is_corresponding":false},{"id":245036,"name":"Andrés J. Garcı́a","orcid":"0000-0001-6602-2518","position":7,"is_corresponding":false},{"id":294499,"name":"Michael D. Hunckler","orcid":"0000-0002-4385-7667","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:49:23.618703Z","pmid":"41030219","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":[]}