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系统甲状旁腺激素 (1-34) 与局部递送中性自组装肽水凝胶联合治疗牙周缺损的实验体内研究。

Combined effects of systemic parathyroid hormone (1-34) and locally delivered neutral self-assembling peptide hydrogel in the treatment of periodontal defects: An experimental in vivo investigation.

机构信息

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Oral Health Science Center, Tokyo Dental College, Tokyo, Japan.

出版信息

J Clin Periodontol. 2019 Oct;46(10):1030-1040. doi: 10.1111/jcpe.13170.

Abstract

AIM

To evaluate in vivo combination therapy of systemic parathyroid hormone (PTH) and locally delivered neutral self-assembling peptide (SAP) hydrogel for periodontal treatment.

MATERIALS AND METHODS

Viability/proliferation of rat periodontal ligament cells in a neutral SAP nanofibre hydrogel (SPG-178) was evaluated using WST-1 assay. Periodontal defects were created mesially to the maxillary first molars in 40 Wistar rats. Defects were filled with 1.5% SPG-178 or left unfilled. Animals received PTH (1-34) or saline injections every 2 days. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing at 2 or 4 weeks postoperative.

RESULTS

At 72 hr, cells in 1.5% SPG-178 showed increased viability/proliferation compared to cells in 0.8% SPG-178 or untreated controls. In vivo, systemic PTH resulted in significantly greater bone volume in the Unfilled group at 2 weeks (p = .01) and 4 weeks (p < .0001) than in the saline control. At 4 weeks, a significantly greater bone volume was observed in the PTH/SPG-178 (p = .0003) and PTH/Unfilled (p = .004) groups than in Saline/SPG-178 group. Histologically, greater bone formation was observed in PTH/SPG-178 at 4 weeks than in other groups. In the PTH/SPG-178 group, increased proportions of PCNA-, VEGF-, and Osterix-positive cells were observed in the treated sites.

CONCLUSIONS

These findings suggest that intermittent systemic PTH and locally delivered neutral SAP hydrogel enhance periodontal healing.

摘要

目的

评估全身甲状旁腺激素(PTH)与局部递呈中性自组装肽(SAP)水凝胶联合治疗牙周病的体内疗效。

材料与方法

采用 WST-1 法评估大鼠牙周膜细胞在中性 SAP 纳米纤维水凝胶(SPG-178)中的活力/增殖情况。在 40 只 Wistar 大鼠上颌第一磨牙近中侧建立牙周缺损,分别用 1.5% SPG-178 或不填充治疗。动物每 2 天接受 PTH(1-34)或生理盐水注射。术后 2 或 4 周,采用 microCT、组织学和免疫组织化学方法评估愈合情况。

结果

在 72 小时,1.5% SPG-178 中的细胞活力/增殖明显高于 0.8% SPG-178 或未处理对照组。体内研究结果显示,与生理盐水对照组相比,2 周(p =.01)和 4 周(p <.0001)时,未填充组的全身 PTH 治疗导致骨量显著增加。4 周时,PTH/SPG-178(p =.0003)和 PTH/未填充组(p =.004)的骨量明显大于 Saline/SPG-178 组。组织学上,4 周时 PTH/SPG-178 组的骨形成明显多于其他组。在 PTH/SPG-178 组中,治疗部位的 PCNA、VEGF 和 Osterix 阳性细胞比例增加。

结论

这些结果表明,间歇性全身 PTH 和局部递呈中性 SAP 水凝胶可增强牙周愈合。

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