{"doi":"10.1002/smll.202506632","title":"Engineered Decellularized Matrix Hydrogels with Crypt–Villus Topography for Forming Functional Intestinal Epithelium","abstract":"Creating a functional intestine model remains challenging owing to the complex topography of the intestinal crypt/villus structure. Here, an inverse molding biofabrication technique is presented to address this challenge. A sacrificial hydrogel mold (SHM) with negative crypt/villus features is first fabricated using digital light processing (DLP) 3D printing of poly(ethylene glycol)-norbornene-tyramine (PEGNB-T) thiol-norbornene hydrogels. Next, decellularized small intestine submucosa-norbornene (dSIS-NB) solution is cast and photopolymerized over the SHM, also via efficient thiol-norbornene photoclick reaction using PEG-tetrathiol as the crosslinker. The hydrogel construct is placed in a buffer solution to induce autonomous and rapid dissolution of the SHM, creating dSIS-NB hydrogels with the positive crypt/villus structure. Intestinal epithelial cells seeded on the dSIS-NB crypt/villus matrices form a confluent monolayer within 3 days and display correct intestinal polarity. Through transepithelial electrical resistance (TEER) measurements and macromolecular transport studies, the new inverse-molded dSIS-NB crypt/villus model further demonstrates the selective and drug-responsive barrier functions. Finally, the unique biofabrication technique is leveraged to create an intestinal disease model carrying regions of both healthy crypts-villi structure and flattened epithelium with hindered macromolecular transport.","journal":"Small","year":2025,"id":522254,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"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":1033244,"name":"Van Thuy Duong","orcid":"0000-0002-7131-4272","position":1,"is_corresponding":false},{"id":1394246,"name":"Jonathan B. Bryan","orcid":null,"position":2,"is_corresponding":false},{"id":277451,"name":"Chien‐Chi Lin","orcid":"0000-0002-4175-8796","position":3,"is_corresponding":false},{"id":1213498,"name":"Ngoc Ha Luong","orcid":"0000-0001-8093-2999","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:49:54.058858Z","pmid":"41124055","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":[]}