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不同等电点的含β-磷酸三钙和重组人成纤维细胞生长因子-2可降解明胶海绵用于牙槽嵴增高的比较:犬鞍状骨缺损的临床前研究。

Comparison between different isoelectric points of biodegradable gelatin sponges incorporating β-tricalcium phosphate and recombinant human fibroblast growth factor-2 for ridge augmentation: A preclinical study of saddle-type defects in dogs.

机构信息

Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Periodontics, Dental Hospital, Tokyo Medical and Dental University, Tokyo, Japan.

出版信息

J Periodontal Res. 2019 Jun;54(3):278-285. doi: 10.1111/jre.12628. Epub 2018 Nov 25.

Abstract

BACKGROUND AND OBJECTIVE

It is well known that recombinant human fibroblast growth factor-2 (rhFGF-2) signaling plays an important role in tissue repair and regeneration. rhFGF-2 strongly binds to acidic gelatin via ionic linkages and is gradually released upon gelatin decomposition. On the other hand, the linkage between rhFGF-2 and basic gelatin is so weak that most rhFGF-2 is rapidly released from basic gelatin by simple desorption. Gelatin/β-tricalcium phosphate (β-TCP) sponges, which comprise 50 wt% gelatin and 50 wt% β-TCP in a cross-linked structure, can release rhFGF-2 gradually owing to their electrical features. In a previous study, we reported that new bone height in the test group using rhFGF-2 with acidic gelatin/β-TCP sponges was significantly greater than that in the control group using acidic gelatin/β-TCP sponges alone in a ridge augmentation model in dogs. However, whether these results depend on controlled release by the gelatin/β-TCP sponges remains controversial. In this study, we evaluated the effects of controlled release by comparing acidic and basic gelatin/β-TCP sponges with different isoelectric points (IEP) on ridge augmentation in dogs.

MATERIALS AND METHODS

Twelve weeks after extraction of the maxillary second and third incisors of six dogs, critically sized saddle-type defects (8 mm length × 4 mm depth) were surgically created bilaterally 2 mm from the mesial side of the canine. Acidic gelatin/β-TCP sponges (IEP 5.0) soaked with 0.3% rhFGF-2 were applied to the defect in the acidic group, whereas basic gelatin/β-TCP sponges (IEP 9.0) soaked with 0.3% rhFGF-2 were applied to the defect in the basic group. Twelve weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography (micro-CT) and histological analyses.

RESULTS

New bone area detected by micro-CT analysis was significantly smaller in the basic group than in the acidic group. New bone height calculated by histologic sections was significantly lower in the basic group than in the acidic group. The total tissue height was lower in the basic group than in the acidic group. However, the differences between both sites were not significant.

CONCLUSIONS

These findings suggest that in ridge augmentation of saddle-type defects, controlled release of rhFGF-2 induces notably more alveolar bone formation than does short-term application of rhFGF-2.

摘要

背景与目的

众所周知,重组人成纤维细胞生长因子-2(rhFGF-2)信号在组织修复和再生中起着重要作用。rhFGF-2 与酸性明胶通过离子键紧密结合,并在明胶分解时逐渐释放。另一方面,rhFGF-2 与碱性明胶的结合非常弱,因此大多数 rhFGF-2 通过简单的解吸作用从碱性明胶中迅速释放。包含 50wt%明胶和 50wt%β-磷酸三钙(β-TCP)的交联结构的明胶/β-TCP 海绵由于其电特性可以逐渐释放 rhFGF-2。在之前的研究中,我们报告了在狗的牙槽嵴增高模型中,使用含有酸性明胶/β-TCP 海绵的 rhFGF-2 的实验组的新骨高度明显大于单独使用酸性明胶/β-TCP 海绵的对照组。然而,这些结果是否取决于明胶/β-TCP 海绵的控制释放仍存在争议。在这项研究中,我们通过比较具有不同等电点(IEP)的酸性和碱性明胶/β-TCP 海绵对狗牙槽嵴增高的影响来评估控制释放的效果。

材料与方法

在六只狗上颌第二和第三切牙拔除 12 周后,在犬齿近端 2mm 处双侧手术创建临界尺寸鞍形缺损(8mm 长×4mm 深)。将含有 0.3%rhFGF-2 的酸性明胶/β-TCP 海绵(IEP5.0)应用于酸性组的缺损处,而将含有 0.3%rhFGF-2 的碱性明胶/β-TCP 海绵(IEP9.0)应用于碱性组的缺损处。手术后 12 周,获取活检标本并进行微计算机断层扫描(micro-CT)和组织学分析。

结果

micro-CT 分析检测到的新骨面积在碱性组明显小于酸性组。通过组织学切片计算的新骨高度在碱性组明显低于酸性组。碱性组的总组织高度低于酸性组,但两组之间的差异无统计学意义。

结论

这些发现表明,在鞍形缺损的牙槽嵴增高中,rhFGF-2 的控制释放比 rhFGF-2 的短期应用明显诱导更多的牙槽骨形成。

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