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通过合理设计磷酸镁水泥加速骨再生。

Accelerated bone regeneration through rational design of magnesium phosphate cements.

机构信息

Department for Functional Materials in Medicine and Dentistry, University Hospital Würzburg, Pleicherwall 2, D-97070 Würzburg, Germany.

Institute for Orthopaedic Research and Biomechanics, Ulm University Medical Center, Helmholtzstraße 14, D-89081 Ulm, Germany.

出版信息

Acta Biomater. 2022 Jun;145:358-371. doi: 10.1016/j.actbio.2022.04.019. Epub 2022 Apr 17.

DOI:10.1016/j.actbio.2022.04.019
PMID:35443213
Abstract

Results of several studies during past years suggested that magnesium phosphate cements (MPCs) not only show excellent biocompatibility and osteoconductivity, but they also provide improved regeneration capacity due to higher solubility compared to calcium phosphates. These findings also highlighted that chemical similarity of bone substitutes to the natural bone tissue is not a determinant factor in the success of regenerative strategies. The aim of this study was to further improve the degradation speed of MPCs for a fast bone ingrowth within a few months. We confirmed our hypothesis, that decreasing the powder-liquid ratio (PLR) of cement results in an increased content of highly soluble phases such as struvite (MgNHPO⋅6HO) as well as K-struvite (MgKPO⋅6HO). Promising compositions with a low PLR of 1 g ml were implanted in partially-loaded tibia defects in sheep. Both cements were partially degraded and replaced by bone tissue after 4 months. The degradation speed of the K-struvite cement was significantly higher compared to the struvite cement, initially resulting in the formation of a cell-rich resorption zone at the surface of some implants, as determined by histology. Overall, both MPCs investigated in this study seem to be promising as an alternative to the clinically well-established, but slowly degrading calcium phosphate cements, depending on defect size and desired degradation rate. Whereas the K-struvite cement might require further modification towards a slower resorption and reduced inflammatory response in vivo, the struvite cement appears promising for the treatment of bone defects due to its continuous degradation with simultaneous new bone formation. STATEMENT OF SIGNIFICANCE: Cold setting bone cements are used for the treatment of bone defects that exceed a critical size and cannot heal on their own. They are applied pasty into the bone defect and harden afterwards so that the shape adapts to the individual defect. Magnesium phosphates such as magnesium ammonium phosphate hexahydrate (struvite) belong to a new class of these cold setting bone cements. They degrade much faster than the clinically established calcium phosphates. In this study, a magnesium phosphate that has hardly been investigated so far was implanted into partially-loaded defects in sheeps: Potassium magnesium phosphate hexahydrate. This showed even faster resorption compared to the struvite cement: after 4 months, 63% of the cement was already degraded.

摘要

过去几年的几项研究结果表明,磷酸镁水泥(MPC)不仅显示出优异的生物相容性和骨诱导性,而且由于其溶解度高于磷酸钙,还提供了改善的再生能力。这些发现还强调,骨替代物与天然骨组织的化学相似性不是再生策略成功的决定因素。本研究的目的是进一步提高 MPC 的降解速度,以在几个月内快速促进骨长入。我们证实了我们的假设,即降低水泥的粉液比(PLR)会导致高溶解度相(如鸟粪石(MgNHPO·6HO)和 K-鸟粪石(MgKPO·6HO))的含量增加。将具有低 PLR(1 g/ml)的有前途的组合物植入绵羊部分负荷胫骨缺损中。两种水泥在 4 个月后部分降解并被骨组织取代。与鸟粪石水泥相比,K-鸟粪石水泥的降解速度明显更快,最初导致一些植入物表面形成富含细胞的吸收区,这通过组织学确定。总体而言,本研究中研究的两种 MPC 似乎都有希望替代临床应用广泛但降解缓慢的磷酸钙水泥,具体取决于缺陷大小和所需的降解速度。虽然 K-鸟粪石水泥可能需要进一步改进,以在体内实现较慢的吸收和减少炎症反应,但鸟粪石水泥似乎有望用于治疗骨缺损,因为它可以持续降解并同时形成新骨。

意义声明

冷固化骨水泥用于治疗超出临界尺寸且无法自行愈合的骨缺损。它们被涂成糊状并涂在骨缺损处,然后变硬,使形状适应个体缺损。六水合磷酸镁铵(鸟粪石)等镁磷酸盐属于这些冷固化骨水泥的一个新类别。它们的降解速度比临床常用的磷酸钙快得多。在这项研究中,一种迄今为止几乎没有被研究过的镁磷酸盐被植入绵羊的部分负荷缺损中:六水合磷酸镁钾。与鸟粪石水泥相比,它的吸收速度更快:4 个月后,63%的水泥已经降解。

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