{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:51:31Z","timestamp":1787028691550,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Point Robotics MedTech Inc.","award":["A-110-091"],"award-info":[{"award-number":["A-110-091"]}]},{"name":"National Science and Technology Council","award":["112-2622-E-038-002"],"award-info":[{"award-number":["112-2622-E-038-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Background: Articular cartilage has limited self-repair capacity. While thermoresponsive poly N-isopropyl acrylamide (pNIPAAm)-based Cell Sheet Engineering (CSE) is a promising scaffold-free strategy, its inherent material properties pose limitations. This study developed and validated a novel, non-thermoresponsive CSE platform for functional cartilage regeneration. Methods: A culture platform was fabricated by grafting the biocompatible polymer poly gamma-glutamic acid (\u03b3-PGA) and a disulfide-containing amino acid onto porous PET membranes. This design enables intact cell sheet detachment with its native extracellular matrix (ECM) via specific cleavage of the disulfide bonds by a mild reducing agent. Results: The hydrated substrate exhibited a biomimetic stiffness (~16.2 MPa) that closely mimics native cartilage. The platform showed superior biocompatibility and supported the cultivation of multi-layered rabbit chondrocyte sheets rich in Collagen II and Glycosaminoglycans. Critically, in a rabbit full-thickness defect model, transplanted autologous cell sheets successfully regenerated integrated, hyaline-like cartilage at 12 weeks, as confirmed by MRI, CT, and histological analyses. Conclusions: This novel CSE platform, featuring highly biomimetic stiffness and a gentle, chemically specific detachment mechanism, represents a highly promising clinical strategy for repairing articular cartilage defects.<\/jats:p>","DOI":"10.3390\/jfb16120437","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T16:31:54Z","timestamp":1764088314000},"page":"437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A New Way to Engineer Cell Sheets for Articular Cartilage Regeneration"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8540-8907","authenticated-orcid":false,"given":"Ta-Lun","family":"Tan","sequence":"first","affiliation":[{"name":"Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-259X","authenticated-orcid":false,"given":"Yuan","family":"Tseng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Biomedical Engineering, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Tse","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4998-7566","authenticated-orcid":false,"given":"Hsuan-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Her-I","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2039-7669","authenticated-orcid":false,"given":"Jun-Jen","family":"Liu","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"},{"name":"School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-8436","authenticated-orcid":false,"given":"Yi-Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"},{"name":"School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"How","family":"Tseng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Reproductive Medicine Center, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Coaccioli, S., Sarzi-Puttini, P., Zis, P., Rinonapoli, G., and Varrassi, G. 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