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While scaffold\u2010free Periodontal ligament stem cells (PDLSCs)\u2010derived cell pellets (CP) and sheets (CS) aid regeneration, the molecular mechanisms and efficacy of PDLSC\u2010CP remain unclear, especially in large animals. This study investigates PDLSC\u2010CP's regenerative potential for Class II defects through in vitro and in vivo analyses. PDLSC\u2010CP demonstrated superior cell viability, improved the extracellular matrix (ECM) quality, enhanced biomechanical properties, and a greater potential for periodontal tissue regeneration compared to PDLSC\u2010CS in both in vitro and in vivo scenarios. Importantly, autocrine transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) in PDLSC\u2010CP upregulated odonto\/osteogenesis\u2010related factors by activating the TGF\u2010\u03b21\/Smad pathway. However, LY2109761, an inhibitor of TGF\u2010\u03b2 receptor I and II, suppressed periodontal tissue regeneration in immunodeficient mice. In the beagle dog with Class II furcation defects, PDLSC\u2010CP regenerated and repaired periodontal bone defects, which is more effective than the control group, the bone substitutes group, and the mixed group (PDLSC\u2010CP and bone substitutes). These findings highlight PDLSC\u2010CP as a promising strategy for periodontal bone defect treatment, where autocrine TGF\u2010\u03b21 stimulates the TGF\u2010\u03b21\/Smad pathway to drive periodontal tissue regeneration.<\/jats:p>","DOI":"10.1002\/adhm.202502553","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:45:36Z","timestamp":1758548736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Autocrine TGF\u2010\u03b21 in Periodontal Ligament\u2010Derived Stem Cell Pellets Enhances Periodontal Regeneration in Class II Furcation Defects of Canine Models"],"prefix":"10.1002","volume":"15","author":[{"given":"Fangfang","family":"Xu","sequence":"first","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"},{"name":"Department of Oral and Maxillofacial Surgery College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"},{"name":"Department of Oral and Maxillofacial Surgery College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siya","family":"Fang","sequence":"additional","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"},{"name":"Department of Oral and Maxillofacial Surgery College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Bai","sequence":"additional","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"},{"name":"Department of Oral and Maxillofacial Surgery College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Gong","sequence":"additional","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"},{"name":"Department of Oral and Maxillofacial Surgery College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Liang","sequence":"additional","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"},{"name":"Department of Oral and Maxillofacial Surgery College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yu","sequence":"additional","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"},{"name":"Department of Oral and Maxillofacial Surgery College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"},{"name":"Department of Oral and Maxillofacial Surgery College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi 710004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6906-8279","authenticated-orcid":false,"given":"Sadam Ahmed","family":"Elayah","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; 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