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三维打印钛合金多孔支架联合反式肉桂醛修复犬股骨头坏死模型

Three-dimensional-printed titanium alloy porous scaffold combined with trans-cinnamaldehyde for repairing osteonecrosis of the femoral head in a dog model.

作者信息

Gao Runzi, Ji Wenhui, Xia Tianwei, Fan Yanxing, Wei Wei, Shi Le, Liu Jinzhu, Zhang Chao, Xue Lezhen, Shen Jirong

机构信息

Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, Jiangsu, China.

Jiangsu Center for Safety Evaluation of Drugs Nanjing 211816, Jiangsu, China.

出版信息

Am J Transl Res. 2020 Mar 15;12(3):1070-1079. eCollection 2020.

Abstract

Osteonecrosis of the femoral head (ONFH) is a common disorder that may be idiopathic, caused by trauma, or associated with alcohol or glucocorticoid use. The goals of early treatment include delaying or avoiding hip replacement, but there are no effective treatments for early-stage disease. The aim of the present study was to evaluate the effects of treatment with 3D-printed porous titanium alloy scaffold combined with daily intraperitoneal trans-cinnamaldehyde (TCA) in a dog model of ONFH. Four weeks after creation of the ONFH model, MRI examination of the femoral head showed the characteristic "double line sign" of ONFH, verifying the validity of our model. After another 12 weeks, femoral head specimens were harvested and examined by gross inspection; micro-computed tomography; histologic staining (hematoxylin and eosin; Masson); immunohistochemical analysis and quantitative real-time polymerase chain reaction analysis. Gross inspection of the femoral head in untreated ONFH animals at 16 weeks after model creation showed pale, exfoliating articular cartilage and disordered trabecular bone. Treatment with 3D-printed titanium alloy porous scaffold combined with TCA ameliorated the pathologic ONFH changes and significantly reduced inmature bone tissue as well as imature collagen in the femoral head, as shown by Masson staining. This treatment also increased VEGF, BMP2, β-catenin, b-FGF, and RUNX2 expression and decreased PPARγ expression, compared with untreated ONFH. In conclusion, 3D-printed titanium alloy porous scaffold combined with TCA can effectively improve ONFH, which may be related to local repair. This provides the theoretical basis for a new treatment strategy for ONFH.

摘要

股骨头坏死(ONFH)是一种常见疾病,可能是特发性的,由创伤引起,或与酒精使用或糖皮质激素使用有关。早期治疗的目标包括延迟或避免髋关节置换,但对于早期疾病尚无有效的治疗方法。本研究的目的是评估3D打印多孔钛合金支架联合每日腹腔注射反式肉桂醛(TCA)治疗在ONFH犬模型中的效果。在建立ONFH模型四周后,对股骨头进行MRI检查显示出ONFH的特征性“双线征”,验证了我们模型的有效性。再过12周后,采集股骨头标本并进行大体检查、显微计算机断层扫描、组织学染色(苏木精和伊红;Masson)、免疫组织化学分析和定量实时聚合酶链反应分析。在模型建立后16周,对未治疗的ONFH动物的股骨头进行大体检查,结果显示关节软骨苍白、剥脱,小梁骨紊乱。如Masson染色所示,3D打印钛合金多孔支架联合TCA治疗改善了ONFH的病理变化,并显著减少了股骨头中的未成熟骨组织以及未成熟胶原蛋白。与未治疗的ONFH相比,这种治疗还增加了VEGF、BMP2、β-连环蛋白、b-FGF和RUNX2的表达,并降低了PPARγ的表达。总之,3D打印钛合金多孔支架联合TCA可有效改善ONFH,这可能与局部修复有关。这为ONFH的新治疗策略提供了理论依据。

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