{"doi":"10.1088/1758-5090/ae235a","title":"Heterogeneous polymerization via two-step crosslinking for tunable microribbon hydrogels","abstract":"Abstract Hydrogels are widely used in tissue engineering, but conventional homogeneous polymerization often creates dense matrices that hinder cell migration and restrict extracellular matrix production. The motivation of this project was to overcome these limitations by developing a heterogeneously crosslinkable hydrogel platform that enables both cell migration and matrix deposition. We present a two-step heterogeneous polymerization approach that introduces spatial variations in matrix density, producing tunable, cell-sized pores that promote migration, proliferation, and matrix synthesis. As an implementation, gelatin was pre-assembled into microribbon-like building blocks using a dynamic molding process, methacrylated to introduce crosslinkable groups, chemically modified, washed, and freeze-dried. Upon rehydration, the ribbons formed a moldable paste that could be mixed with cells and photo-crosslinked into scaffolds with in situ –formed, cell-sized pores. The main novelty of this method is the introduction of chemical modifications with methacrylic anhydride (MAA), acetic anhydride (AceA), and succinic anhydride (SucA), which enable a controlled two-step heterogeneous polymerization and allow independent tuning of scaffold microstructure, mechanics, and degradation. AceA reduced crosslink density and accelerated degradation, whereas SucA promoted swelling, enhanced mechanical strength, and slowed degradation. Cell studies revealed that SucA-modified scaffolds supported superior adhesion and proliferation compared to AceA-modified and unmodified controls. Such work may significantly impact the design of next-generation scaffolds by providing a versatile platform that integrates structural, mechanical, and biochemical control for regenerative medicine applications.","journal":"Biofabrication","year":2025,"id":582971,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"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":1290962,"name":"Fereshteh Ahadi","orcid":null,"position":1,"is_corresponding":false},{"id":1494889,"name":"Niloofar Esmati","orcid":"0000-0002-8744-635X","position":2,"is_corresponding":false},{"id":1143029,"name":"Mingyue Fan","orcid":"0000-0002-8365-7571","position":3,"is_corresponding":false},{"id":284004,"name":"Lin Han","orcid":"0000-0003-4180-1288","position":4,"is_corresponding":false},{"id":1494890,"name":"Christopher Y. Li","orcid":"0000-0003-2431-7099","position":5,"is_corresponding":false},{"id":1290439,"name":"Li‐Hsin Han","orcid":"0000-0002-0135-2863","position":6,"is_corresponding":false},{"id":1290437,"name":"Mahsa Karimi","orcid":"0000-0002-9833-9699","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:58:59.653747Z","pmid":"41285045","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":[]}