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基于透辉石钙镁硅酸盐陶瓷的杂交植入物作为重组 BMP-2 的载体和脱矿骨基质作为支架:在小鼠颅骨切开模型中的修复性骨生成动力学。

Hybrid Implants Based on Calcium-Magnesium Silicate Ceramics Diopside as a Carrier of Recombinant BMP-2 and Demineralized Bone Matrix as a Scaffold: Dynamics of Reparative Osteogenesis in a Mouse Craniotomy Model.

机构信息

Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation, Moscow, 123098, Russia.

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.

出版信息

Biochemistry (Mosc). 2022 Nov;87(11):1277-1291. doi: 10.1134/S0006297922110074.

DOI:10.1134/S0006297922110074
PMID:36509727
Abstract

Calcium-magnesium silicate ceramics, diopside, is a promising material for use in bone plastics, but until now the possibility of its use as a carrier of recombinant bone morphogenetic protein-2 (BMP-2) has not been studied, as well as the features of reparative osteogenesis mediated by the materials based on diopside with BMP-2. Powder of calcium-magnesium silicate ceramics was obtained by solid-state synthesis using biowaste - rice husks and egg shells - as source components. Main phase of the obtained ceramics was diopside. The obtained particles were irregularly shaped with an average size of about 2.3 μm and ~20% porosity; average pore size was about 24 nm, which allowed the material to be classified as mesoporous. Diopside powder adsorbs more than 150 μg of recombinant BMP-2 per milligram, which exceeds binding capacity of hydroxyapatite, a calcium-phosphate ceramic often used in hybrid implants, by more than 3 times. In vitro release kinetics of BMP-2 was characterized by a burst release in the first 2 days and a sustained release of approximately 0.4 to 0.5% of the loaded protein over the following 7 days. In vivo experiments were performed with a mouse model of cranial defects of critical size with implantation of a suspension of diopside powder with/without BMP-2 in hyaluronic acid incorporated into the disks of demineralized bone matrix with 73-90% volume porosity and macropore size from 50 to 650 μm. Dynamics of neoosteogenesis and bone tissue remodeling was investigated histologically at the time points of 12, 21, 48, and 63 days. Diopside particles were evenly spread in the matrix and caused minimal foreign body reaction. In the presence of BMP-2 by the day 63 significant foci of newly formed bone tissue were formed in the implant pores with bone marrow areas, moreover, large areas of demineralized bone matrix in the implant center and maternal bone at the edges were involved in the remodeling. Diopside could be considered as a promising material for introduction into hybrid implants as an effective carrier of BMP-2.

摘要

硅酸钙镁陶瓷,透辉石,是一种有前途的骨塑料材料,但直到现在,其作为重组骨形态发生蛋白-2(BMP-2)载体的可能性尚未得到研究,以及基于透辉石和 BMP-2 的材料介导的修复性骨生成的特征。硅酸钙镁陶瓷粉末通过使用生物废料 - 稻壳和蛋壳 - 作为源成分的固态合成获得。所得陶瓷的主要相为透辉石。所得颗粒形状不规则,平均粒径约为 2.3 μm,孔隙率约为 20%;平均孔径约为 24nm,可将材料归类为中孔。透辉石粉末每毫克可吸附超过 150μg 的重组 BMP-2,这超过了羟基磷灰石(一种常用于混合植入物的钙磷酸盐陶瓷)的结合能力,超过 3 倍。BMP-2 的体外释放动力学表现为前 2 天的爆发释放,随后 7 天内负载蛋白的持续释放约为 0.4 至 0.5%。在体内实验中,使用临界大小颅骨缺损的小鼠模型进行实验,将透辉石粉末的悬浮液(有/无 BMP-2)植入到含 73-90%体积孔隙率和 50-650μm 大孔尺寸的脱矿骨基质盘的透明质酸中。在 12、21、48 和 63 天的时间点,通过组织学研究新骨生成和骨组织重塑的动力学。透辉石颗粒均匀分布在基质中,引起最小的异物反应。在第 63 天,在植入物孔中有新形成的骨组织形成明显的焦点,并且在植入物中心和边缘的母体骨中有大的脱矿骨基质区域参与重塑。透辉石可用作引入混合植入物的有前途的材料,作为 BMP-2 的有效载体。

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