In reconstructive surgery, complications post-fibula free flap (FFF) reconstruction, notably periimplant hyperplasia, are significant yet understudied. This study analyzed peri-implant hyperplastic tissue surrounding FFF, alongside peri-implantitis and foreign body granulation (FBG) tissues from patients treated at the Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital. Using light microscopy, pseudoepitheliomatous hyperplasia, anucleate and pyknotic prickle cells, and excessive collagen deposition were observed in FFF hyperplastic tissue. Ultrastructural analyses revealed abnormal structures, including hemidesmosome dilation, bacterial invasion, and endoplasmic reticulum (ER) swelling. In immunohistochemical analysis, unfolded protein-response markers ATF6, PERK, XBP1, inflammatory marker NFκB, necroptosis marker MLKL, apoptosis marker GADD153, autophagy marker LC3, epithelial–mesenchymal transition, and angiogenesis markers were expressed variably in hyperplastic tissue surrounding FFF implants, peri-implantitis, and FBG tissues. NFκB expression was higher in peri-implantitis and FBG tissues compared to hyperplastic tissue surrounding FFF implants. PERK expression exceeded XBP1 significantly in FFF hyperplastic tissue, while expression levels of PERK, XBP1, and ATF6 were not significantly different in periimplantitis and FBG tissues. These findings provide valuable insights into the interconnected roles of ER stress, necroptosis, apoptosis, and angiogenesis in the pathogenesis of oral pathologies, offering a foundation for innovative strategies in dental implant rehabilitation management and prevention.
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