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两种可吸收非交联胶原膜引导骨再生的组织动力学和再生效果:体内临床前分子和组织学研究。

Tissue dynamics and regenerative outcome in two resorbable non-cross-linked collagen membranes for guided bone regeneration: A preclinical molecular and histological study in vivo.

机构信息

Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.

出版信息

Clin Oral Implants Res. 2018 Jan;29(1):7-19. doi: 10.1111/clr.13032. Epub 2017 Jul 13.

DOI:10.1111/clr.13032
PMID:28703398
Abstract

OBJECTIVES

To investigate the molecular and structural patterns of bone healing during guided bone regeneration (GBR), comparing two resorbable non-cross-linked collagen membranes.

MATERIALS AND METHODS

Trabecular bone defects in rat femurs were filled with deproteinized bovine bone (DBB) and covered with either a membrane comprising collagen and elastin (CXP) or collagen (BG). Samples were harvested after 3 and 21 days for histology/histomorphometry and gene expression analysis. Gene expression analysis was performed on the membrane (at 3 days) and the underlying defect compartment (at 3 and 21 days).

RESULTS

At the total defect level, no differences in bone area percentage were found between the CXP and BG. When evaluating the central area of the defect, a higher percentage of de novo bone formation was seen for the CXP membrane (34.9%) compared to BG (15.5%) at 21 days (p = .01). Gene expression analysis revealed higher expression of bone morphogenetic protein-2 (Bmp2) in the membrane compartment at 3 days in the BG group. By contrast, higher Bmp2 expression was found in the defect compartment treated with the CXP membrane, both at 3 and 21 days. A significant temporal increase (from 3 to 21 days) in the remodeling activity, cathepsin K (Catk) and calcitonin receptor (Calcr), was found in the CXP group. Molecular analysis demonstrated expression of several growth factors and cytokines in the membrane compartment irrespective of the membrane type. Bmp2 expression in the membrane correlated positively with Bmp2 expression in the defect, whereas fibroblast growth factor-2 (Fgf2) expression in the membrane correlated positively with inflammatory cytokines, tumor necrosis factor-alpha (Tnfa) and interleukin-6 (Il6) in the defect.

CONCLUSIONS

The results provide histological and molecular evidence that different resorbable collagen membranes contribute differently to the GBR healing process. In the BG group, bone formation was primarily localized to the peripheral part of the defect. By contrast, the CXP group demonstrated significantly higher de novo bone formation in the central portion of the defect. This increase in bone formation was reflected by triggered expression of potent osteogenic growth factor, Bmp2, in the defect. These findings suggest that the CXP membrane may have a more active role in regulating the bone healing dynamics.

摘要

目的

通过比较两种可吸收非交联胶原膜,研究引导骨再生(GBR)过程中骨愈合的分子和结构模式。

材料和方法

在大鼠股骨的小梁骨缺损中填充脱蛋白牛骨(DBB),并用包含胶原蛋白和弹性蛋白的膜(CXP)或胶原蛋白(BG)覆盖。在第 3 天和第 21 天采集样本进行组织学/组织形态计量学和基因表达分析。在第 3 天对膜(在第 3 天)和下方的缺陷区(在第 3 天和第 21 天)进行基因表达分析。

结果

在总缺陷水平上,CXP 和 BG 之间的骨面积百分比无差异。在评估缺陷中央区域时,CXP 膜的新骨形成比例更高(34.9%),而 BG 为 15.5%(p=0.01)。在第 21 天,基因表达分析显示 BG 组在膜区 Bmp2 的表达更高。相比之下,CXP 膜处理的缺陷区在第 3 天和第 21 天 Bmp2 的表达更高。在 CXP 组中,在第 3 天和第 21 天,组织改建活性、组织蛋白酶 K(Catk)和降钙素受体(Calcr)均呈显著的时间增加。分子分析显示,无论膜类型如何,膜区均表达几种生长因子和细胞因子。膜区的 Bmp2 表达与缺陷区的 Bmp2 表达呈正相关,而膜区的成纤维细胞生长因子-2(Fgf2)表达与缺陷区的炎症细胞因子、肿瘤坏死因子-α(Tnfa)和白细胞介素-6(Il6)呈正相关。

结论

这些结果提供了组织学和分子证据,表明不同的可吸收胶原膜对 GBR 愈合过程的贡献不同。在 BG 组中,骨形成主要局限于缺陷的外周部分。相比之下,CXP 组在缺陷的中央部分显示出明显更高的新骨形成。这种骨形成的增加反映在缺陷中触发表达的强力成骨生长因子 Bmp2。这些发现表明 CXP 膜在调节骨愈合动力学方面可能具有更积极的作用。

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