Objectives: Angiogenesis is an important feature in inflammation and healing. Indeed, vessel density and vascular related growth factors play a bivalent role i.e. either sustaining the healing processes or participating in the inflammation-related tissue damage. So far no studies have described the vascular changes occurring over time within peri-implant tissues by an analysis of sequential histological biopsies. Recent advances in the understating of the physiological function of tissue transglutaminase 2 (TG2), a multi functional protein cross-linking enzyme that stabilizes tissues, have demonstrated that TG2 plays a central role in the control of fibroblast activity and matrix engineering through different functions. We hypothesized that the number of the small size (probably immature) vessel structures, along with the distribution of TG2 in peri-implant tissue, might play a key role in the development of an abnormal wound healing in the peri-implant soft tissue possibly leading to gingival overgrowth. The aim of this study was to determine if there was any correlation between neo-angiogenesis and peri-implant soft tissues maturation processes. Methods: Edentulous patients undergoing mandibular implant retained rehabilitation were included in the study. Biopsies of the peri-implant mucosa were performed at the first surgical stage and at 4, 8, 12 months after prosthetic load. An evaluation of the vessels density was carried out by digital virtual microscopy and by an immunohistochemistry approach (antibodies antiCD31, antiTG2). A multiple regression model has been performed for statistical analysis. Results: In one third of the patients an increased blood vessel density, gingival overgrowth and an augmented TG2 expression within the extracellular matrix (ECM) were observed. The multiple regression model presents a significant positive association between probing depth at baseline and TG2 at visit 3 (beta= 32.2, p=0.01). Conclusions: Number and type of neo-vessels as well as distribution of TG2 in peri-implant tissue may vary. The association of an increased TG2 expression in the ECM with a small size (probably immature) vessel structures, might have a significant impact in the development of gingival overgrowth around loaded implant.
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