Abstract：
OBJECTIVE: The aim of this study is to assess early wound healing expression of local angiogenic biomarkers following connective tissue graft (CTG) at dental implant sites.
METHODS: Twenty-eight subjects with single dental implants exhibiting a soft tissue dehiscence were included and randomly treated with CTG, either with coronally advanced flap (CAF) or with tunnel technique (TUN). Peri-implant crevicular fluid (PICF) was collected at the midfacial and midlingual aspect of the implant sites at baseline and at 3, 7, 14, 30, and 90 days after the surgical intervention. The expression of angiogenin (ANG), fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinases-2 (TIMP-2), and vascular endothelial growth factor (VEGF) was investigated over a period of 3 months. Patient-reported outcomes, clinical measurements, and ultrasonography scans at multiple time points were also evaluated.
RESULTS: The longitudinal regression revealed a significant difference in the expression of VEGF and TIMP-2 between CAF- and TUN-treated sites over 3 months (p = .033 and p = .004, respectively), whereas no significant differences were observed for ANG, FGF-2 and PDGF between the two groups. At 7 days, a direct correlation was observed between ANG levels and ultrasonographic color velocity in the CAF group (p < .001) and between ANG levels and ultrasonographic color power in the TUN group (p = .028). VEGF levels and ultrasonographic mean perfused area of the CTG were significantly correlated at the 7-day time point (p < .001 for both CAF and TUN). The expression of VEGF at 7 days was directly associated with mucosal thickness gain at 1 year (p < .001 for both groups). Early TIMP-2 expression showed an inverse correlation with time to recovery (p = .002). TIMP-2 levels at 3 months exhibited inverse correlations with mean dehiscence coverage (p = .004) and the rate of complete dehiscence coverage (p = .012).
CONCLUSIONS: PICF biomarkers can be used to monitor early wound healing events following soft tissue grafting at implant sites. VEGF and TIMP-2 showed correlations with the 1-year clinical and volumetric outcomes, as well as with post-operative patient-reported outcomes and Doppler Ultrasonographic tissue perfusion-related parameters.
METHODS: Twenty-eight subjects with single dental implants exhibiting a soft tissue dehiscence were included and randomly treated with CTG, either with coronally advanced flap (CAF) or with tunnel technique (TUN). Peri-implant crevicular fluid (PICF) was collected at the midfacial and midlingual aspect of the implant sites at baseline and at 3, 7, 14, 30, and 90 days after the surgical intervention. The expression of angiogenin (ANG), fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinases-2 (TIMP-2), and vascular endothelial growth factor (VEGF) was investigated over a period of 3 months. Patient-reported outcomes, clinical measurements, and ultrasonography scans at multiple time points were also evaluated.
RESULTS: The longitudinal regression revealed a significant difference in the expression of VEGF and TIMP-2 between CAF- and TUN-treated sites over 3 months (p = .033 and p = .004, respectively), whereas no significant differences were observed for ANG, FGF-2 and PDGF between the two groups. At 7 days, a direct correlation was observed between ANG levels and ultrasonographic color velocity in the CAF group (p < .001) and between ANG levels and ultrasonographic color power in the TUN group (p = .028). VEGF levels and ultrasonographic mean perfused area of the CTG were significantly correlated at the 7-day time point (p < .001 for both CAF and TUN). The expression of VEGF at 7 days was directly associated with mucosal thickness gain at 1 year (p < .001 for both groups). Early TIMP-2 expression showed an inverse correlation with time to recovery (p = .002). TIMP-2 levels at 3 months exhibited inverse correlations with mean dehiscence coverage (p = .004) and the rate of complete dehiscence coverage (p = .012).
CONCLUSIONS: PICF biomarkers can be used to monitor early wound healing events following soft tissue grafting at implant sites. VEGF and TIMP-2 showed correlations with the 1-year clinical and volumetric outcomes, as well as with post-operative patient-reported outcomes and Doppler Ultrasonographic tissue perfusion-related parameters.
摘要：
目的：本研究的目的是评估种植区结缔组织移植（CTG）后早期伤口愈合中局部血管生成生物标志物的表达。
方法：纳入了28名接受单种植牙表现出软组织裂开的受试者，并随机接受CTG治疗，无论是冠状推进皮瓣（CAF）或隧道技术（TUN）。在基线和手术干预后3、7、14、30和90天时，在植入部位的中面部和中舌侧收集植入物周围液（PICF）。血管生成素（ANG）的表达，成纤维细胞生长因子-2(FGF-2),血小板衍生生长因子(PDGF),金属蛋白酶-2的组织抑制剂（TIMP-2），和血管内皮生长因子（VEGF）在3个月的时间内进行了研究。患者报告的结果，临床测量，我们还评估了多个时间点的超声扫描.
结果：纵向回归显示，在3个月内，CAF和TUN处理部位之间VEGF和TIMP-2的表达存在显着差异（分别为p=.033和p=.004），而ANG没有观察到显著差异，FGF-2和PDGF介于两组之间。在7天,在CAF组(p<.001)和TUN组(p=.028)中,ANG水平与超声彩色功率之间存在直接相关性.在7天时间点，VEGF水平和CTG的超声平均灌注面积显着相关（CAF和TUN的p<.001）。7天时VEGF的表达与1年时的粘膜厚度增加直接相关（两组p<.001）。早期TIMP-2表达与恢复时间呈负相关(p=0.002)。3个月时的TIMP-2水平与平均开裂覆盖率（p=.004）和完全开裂覆盖率（p=.012）呈负相关。
结论：PICF生物标志物可用于监测植入部位软组织移植后的早期伤口愈合事件。VEGF和TIMP-2显示与1年临床和体积结果相关，以及术后患者报告的结局和多普勒超声检查组织灌注相关参数。
方法：纳入了28名接受单种植牙表现出软组织裂开的受试者，并随机接受CTG治疗，无论是冠状推进皮瓣（CAF）或隧道技术（TUN）。在基线和手术干预后3、7、14、30和90天时，在植入部位的中面部和中舌侧收集植入物周围液（PICF）。血管生成素（ANG）的表达，成纤维细胞生长因子-2(FGF-2),血小板衍生生长因子(PDGF),金属蛋白酶-2的组织抑制剂（TIMP-2），和血管内皮生长因子（VEGF）在3个月的时间内进行了研究。患者报告的结果，临床测量，我们还评估了多个时间点的超声扫描.
结果：纵向回归显示，在3个月内，CAF和TUN处理部位之间VEGF和TIMP-2的表达存在显着差异（分别为p=.033和p=.004），而ANG没有观察到显著差异，FGF-2和PDGF介于两组之间。在7天,在CAF组(p<.001)和TUN组(p=.028)中,ANG水平与超声彩色功率之间存在直接相关性.在7天时间点，VEGF水平和CTG的超声平均灌注面积显着相关（CAF和TUN的p<.001）。7天时VEGF的表达与1年时的粘膜厚度增加直接相关（两组p<.001）。早期TIMP-2表达与恢复时间呈负相关(p=0.002)。3个月时的TIMP-2水平与平均开裂覆盖率（p=.004）和完全开裂覆盖率（p=.012）呈负相关。
结论：PICF生物标志物可用于监测植入部位软组织移植后的早期伤口愈合事件。VEGF和TIMP-2显示与1年临床和体积结果相关，以及术后患者报告的结局和多普勒超声检查组织灌注相关参数。
