{"doi":"10.1126/sciadv.aaz5913","title":"Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell–based cartilage tissue engineering","abstract":"Despite great progress in biomaterial design strategies for replacing damaged articular cartilage, prevention of stem cell-derived chondrocyte hypertrophy and resulting inferior tissue formation is still a critical challenge. Here, by using engineered biomaterials and a high-throughput system for screening of combinatorial cues in cartilage microenvironments, we demonstrate that biomaterial cross-linking density that regulates matrix degradation and stiffness-together with defined presentation of growth factors, mechanical stimulation, and arginine-glycine-aspartic acid (RGD) peptides-can guide human mesenchymal stem cell (hMSC) differentiation into articular or hypertrophic cartilage phenotypes. Faster-degrading, soft matrices promoted articular cartilage tissue formation of hMSCs by inducing their proliferation and maturation, while slower-degrading, stiff matrices promoted cells to differentiate into hypertrophic chondrocytes through Yes-associated protein (YAP)-dependent mechanotransduction. in vitro and in vivo chondrogenesis studies also suggest that down-regulation of the Wingless and INT-1 (WNT) signaling pathway is required for better quality articular cartilage-like tissue production.","journal":"Science Advances","year":2020,"id":59990,"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":64,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316471,"name":"Oju Jeon","orcid":"0000-0003-3972-9272","position":1,"is_corresponding":false},{"id":203248,"name":"Ming Kong","orcid":null,"position":2,"is_corresponding":false},{"id":278758,"name":"Amr A. Abdeen","orcid":"0000-0003-4071-6620","position":3,"is_corresponding":false},{"id":244207,"name":"Jung‐Youn Shin","orcid":null,"position":4,"is_corresponding":false},{"id":316472,"name":"Ha Neul Lee","orcid":"0000-0002-2284-4947","position":5,"is_corresponding":false},{"id":316473,"name":"Yu Bin Lee","orcid":"0000-0002-1470-6499","position":6,"is_corresponding":false},{"id":241784,"name":"Wujin Sun","orcid":"0000-0002-3167-111X","position":7,"is_corresponding":false},{"id":316474,"name":"Praveen Bandaru","orcid":"0000-0002-8522-7778","position":8,"is_corresponding":false},{"id":316475,"name":"Daniel S. Alt","orcid":"0000-0002-8058-0644","position":9,"is_corresponding":false},{"id":241783,"name":"KangJu Lee","orcid":"0000-0003-2166-0916","position":10,"is_corresponding":false},{"id":241785,"name":"Han‐Jun Kim","orcid":"0000-0001-9238-7238","position":11,"is_corresponding":false},{"id":316476,"name":"Sang Jin Lee","orcid":"0000-0002-8007-8785","position":12,"is_corresponding":false},{"id":316477,"name":"Somali Chaterji","orcid":"0000-0002-3651-6362","position":13,"is_corresponding":false},{"id":241430,"name":"Su Ryon Shin","orcid":"0000-0003-0864-6482","position":14,"is_corresponding":false},{"id":243151,"name":"Eben Alsberg","orcid":"0000-0002-3487-4625","position":15,"is_corresponding":false},{"id":230339,"name":"Ali Khademhosseini","orcid":"0000-0002-2692-1524","position":16,"is_corresponding":false},{"id":241786,"name":"Junmin Lee","orcid":"0000-0002-4414-7130","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T21:08:47.852401Z","pmid":"32494742","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":[]}