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镓增强了磷酸钙骨生物材料的修复性能。

Gallium enhances reconstructive properties of a calcium phosphate bone biomaterial.

机构信息

Université Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice, France.

GRAFTYS SA, Aix en Provence, France.

出版信息

J Tissue Eng Regen Med. 2018 Feb;12(2):e854-e866. doi: 10.1002/term.2396. Epub 2017 May 23.

DOI:10.1002/term.2396
PMID:28079305
Abstract

Calcium phosphate (CaP)-based biomaterials are commonly used in bone reconstructive surgery to replace the damaged tissue, and can also serve as vectors for local drug delivery. Due to its inhibitory action on osteoclasts, the semi-metallic element gallium (Ga) is used for the systemic treatment of disorders associated with accelerated bone resorption. As it was demonstrated that Ga could be incorporated in the structure of CaP biomaterials, we investigated the biological properties of Ga-loaded CaP biomaterials. Culturing bone cells on Ga-CaP, we observed a decrease in osteoclast number and a downregulation of late osteoclastic markers expression, while Ga-CaP upregulated the expression of osteoblastic marker genes involved in the maturation of bone matrix. We next investigated in vivo bone reconstructive properties of different Ga-loaded biomaterials using a murine bone defect healing model. All implanted biomaterials showed a good osseointegration into the surrounding host tissue, accompanied by a successful bone ingrowth and bone marrow reconstruction, as evidenced by histological analysis. Moreover, quantitative micro-computed tomography analysis of implants revealed that Ga enhanced total defect filling. Lastly, we took advantage for the first time of a particular mode of non-linear microscopy (second harmonic generation) to quantify in vivo bone tissue reconstruction within a CaP bone substitute. By doing so, we showed that Ga exerted a positive impact on mature organized collagen synthesis. As a whole, our data support the hypothesis that Ga represents an attractive additive to CaP biomaterials for bone reconstructive surgery. Copyright © 2017 John Wiley & Sons, Ltd.

摘要

钙磷酸盐(CaP)基生物材料常用于骨修复手术中,以替代受损组织,也可用作局部药物递送的载体。由于半金属元素镓(Ga)对破骨细胞具有抑制作用,因此被用于治疗与加速骨吸收相关的疾病的全身治疗。由于已经证明 Ga 可以掺入 CaP 生物材料的结构中,因此我们研究了负载 Ga 的 CaP 生物材料的生物学特性。在 Ga-CaP 上培养骨细胞时,我们观察到破骨细胞数量减少,晚期破骨细胞标志物表达下调,而 Ga-CaP 则上调了参与骨基质成熟的成骨细胞标记基因的表达。接下来,我们使用小鼠骨缺损愈合模型研究了不同负载 Ga 的生物材料的体内骨重建特性。所有植入的生物材料均与周围宿主组织良好地整合,组织学分析表明,成功地进行了骨内生长和骨髓重建。此外,对植入物的定量微计算机断层扫描分析表明,Ga 增强了总缺陷填充。最后,我们首次利用非线性显微镜(二次谐波产生)的特殊模式来定量体内 CaP 骨替代物内的骨组织重建。通过这样做,我们表明 Ga 对成熟的有组织的胶原合成具有积极影响。总体而言,我们的数据支持 Ga 代表用于骨修复手术的 CaP 生物材料的有吸引力的添加剂的假设。版权所有©2017 年 John Wiley & Sons,Ltd.

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