{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T18:35:35Z","timestamp":1787337335870,"version":"build-2736575974"},"reference-count":68,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"34","funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CMMI 1548571"],"award-info":[{"award-number":["CMMI 1548571"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01 AR07787"],"award-info":[{"award-number":["K01 AR07787"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 R077700"],"award-info":[{"award-number":["R21 R077700"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AR069619"],"award-info":[{"award-number":["P30 AR069619"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL163168"],"award-info":[{"award-number":["R01 HL163168"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 R077700"],"award-info":[{"award-number":["R21 R077700"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 R077700"],"award-info":[{"award-number":["R21 R077700"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 AR080581"],"award-info":[{"award-number":["P50 AR080581"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 AR080581"],"award-info":[{"award-number":["P50 AR080581"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL163168"],"award-info":[{"award-number":["R01 HL163168"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Pennsylvania Health-Tech Accelerator Award"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 AR080581"],"award-info":[{"award-number":["P50 AR080581"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Penn Health-Tech Accelerator Award","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AR069619"],"award-info":[{"award-number":["P30 AR069619"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL163168"],"award-info":[{"award-number":["R01 HL163168"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Pennsylvania Health-Tech Accelerator Award"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:p>The rotator cuff plays a vital role in shoulder movement and joint stability. Unfortunately, tears at the rotator cuff enthesis are common and frequently lead to retears after surgical intervention, particularly at the suture location and its anchor sites. These failures are typically due to the inability of current surgical treatments to mimic the native tissue complexity and provide the necessary metabolic, bioactive, and biophysical cues for effective enthesis regeneration. In this study, we engineered a biomimetic multiphasic scaffold system (BMS) to integrate with conventional suture anchor systems and deliver spatially organized structural and biological cues to enhance enthesis regeneration. The BMS consists of three distinct phases: Phase 1 features an aligned, nanofibrous decellularized tendon extracellular matrix (dECM) combined with \u201cstiff\u201d methacrylated hyaluronic acid (MeHA); phase 2 incorporates nonaligned, nanofibrous dECM with \u201csoft\u201d MeHA; and phase 3 uses a porous, bioenergetic, citrate-based composite scaffold for bone integration. In vitro, the BMS notably enhanced tenogenic, fibrochondrogenic, and chondrogenic differentiation, facilitating zone-specific rotator cuff enthesis regeneration. Further, in vivo, the BMS promoted successful integrative healing, forming distinct tendon, fibrocartilage, and bone regions at the repair site. This advanced multiphasic scaffold closely replicates native tissue properties, offering a promising strategy to improve rotator cuff repair. Its integration with conventional suture anchors provides an innovative design that enhances mechanical fixation and guides enthesis healing to reduce retear rates. Broadly, this platform offers a versatile solution for biointegrative repair strategies across complex soft-to-hard tissue interfaces.<\/jats:p>","DOI":"10.1126\/sciadv.aea3128","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:58:41Z","timestamp":1787335121000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Engineering a biomimetic multiphasic suture anchor system for enhanced rotator cuff enthesis regeneration"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4038-3319","authenticated-orcid":true,"given":"Zizhao","family":"Li","sequence":"first","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-2436","authenticated-orcid":true,"given":"Se-Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0102-4984","authenticated-orcid":true,"given":"Lin","family":"Xu","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqiang","family":"Lu","sequence":"additional","affiliation":[{"name":"Acuitive Technologies Inc., Allendale, NJ 07401, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5089-6796","authenticated-orcid":true,"given":"Ellen Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-3055","authenticated-orcid":true,"given":"Dong Hwa","family":"Kim","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bat-Ider","family":"Tumenbayar","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-2315","authenticated-orcid":true,"given":"Tyler E.","family":"Blanch","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeun","family":"Jung","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4658-8065","authenticated-orcid":true,"given":"Jayden","family":"Shin","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-1652","authenticated-orcid":true,"given":"Yongho","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Pathology and Anatomical Sciences and Department of Biomedical Engineering, University at Buffalo, Buffalo, NY 14203, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T.","family":"Tran","sequence":"additional","affiliation":[{"name":"Acuitive Technologies Inc., Allendale, NJ 07401, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-8212","authenticated-orcid":true,"given":"Thomas","family":"Schaer","sequence":"additional","affiliation":[{"name":"Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2771-5076","authenticated-orcid":true,"given":"Su Chin","family":"Heo","sequence":"additional","affiliation":[{"name":"McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Translational Musculoskeletal Research Center, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.32098\/mltj.03.2014.12"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1998.19340481.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2018.01.006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.9050"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.5312\/wjo.v6.i11.902"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4055\/cios.2018.10.2.119"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4329\/wjr.v9.i3.126"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arthro.2013.06.015"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200402000-00002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4055\/cios20317"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40634-023-00608-w"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/BTO.0000000000000168"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2018.0019"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jse.2011.11.016"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.08.035"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jse.2024.05.002"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00167-023-07383-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2024.10.015"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2025.1629816"},{"key":"e_1_3_2_21_2","first-page":"35","article-title":"The development and morphogenesis of the tendon-to-bone insertion - what development can teach us about healing","volume":"10","author":"Thomopoulos S.","year":"2010","unstructured":"S. Thomopoulos, G. M. Genin, L. M. Galatz, The development and morphogenesis of the tendon-to-bone insertion - what development can teach us about healing. J. Musculoskelet. Neuronal Interact. 10, 35\u201345 (2010).","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.03.004"},{"key":"e_1_3_2_23_2","first-page":"510","article-title":"Biomimetic multizonal scaffolds for the reconstruction of zonal articular cartilage in chondral and osteochondral defects","volume":"43","author":"Lin X.","year":"2025","unstructured":"X. Lin, Y. Zhang, J. Li, B. G. Oliver, B. Wang, H. Li, K. T. Yong, J. J. Li, Biomimetic multizonal scaffolds for the reconstruction of zonal articular cartilage in chondral and osteochondral defects. Bioact. Mater. 43, 510\u2013549 (2025).","journal-title":"Bioact. Mater."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.09.017"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10110"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2011.0705"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2013.12.012"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.03.074"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.04.004"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.8b01276"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/bm049508a"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-matsci-070214-020815"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1039\/c001605e"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.4018\/ijbre.2011010102"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2005.05.106"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.04.017"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.34272"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/term.2017"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.01.061"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/nano13162287"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1343030"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actamat.2007.01.029"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2017.07.014"},{"key":"e_1_3_2_44_2","unstructured":"I. O. f. Standardization (International Organization for Standardization (ISO) 2014) vol. ISO 23317:2014 pp. 13."},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","unstructured":"C. Rey C. Combes C. Drouet D. Grossin G. Bertrand J. Souli\u00e9 in Comprehensive Biomaterials II P. Ducheyne Ed. (Elsevier 2017) vol. 1 pp. 244\u2013290.","DOI":"10.1016\/B978-0-12-803581-8.10171-7"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.801829"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arthro.2007.01.023"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-021-00579-4"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3904"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1369\/0022155412456380"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23869"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2024.0272"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.5c01283"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00064-021-00754-3"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12178-020-09658-4"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13175066"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.2174\/1874325001610010315"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.02.013"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/bm200415g"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz849"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S123236"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099588"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2017.01.074"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.7b01583"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1063\/5.0157549"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10570-017-1612-3"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.257709"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1063\/5.0239035"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2014.10.030"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aea3128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:59:27Z","timestamp":1787335167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aea3128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":68,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2026,8,21]]}},"alternative-id":["10.1126\/sciadv.aea3128"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aea3128","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"assertion":[{"value":"2025-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaea3128"}}