Electrospun, synthetic bone void filler promotes human MSC function and BMP-2 mediated spinal fusion.

Electrospun, synthetic bone void filler promotes human MSC function and BMP-2 mediated spinal fusion.
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DOI:
10.1177/0885328220937999
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发表时间:
2020-10
影响因子:
2.9
通讯作者:
W Bae H
W Bae H
中科院分区:
工程技术4区
文献类型:
--
作者:
Glaeser JD;Salehi K;Kanim LE;Ju DG;Hyuk Yang J;Behrens PH;Eberlein SA;Metzger MF;Arabi Y;Stefanovic T;Sheyn D;W Bae H

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在脊柱融合术中,合成骨移植物常用于获得良好巩固的融合块。这些骨移植物作为支架,理想地支持细胞功能和促进蛋白质结合。目的是表征电纺丝合成骨空洞填充物(Reb)的骨形态发生蛋白(BMP)-2释放特性和体外对人间充质干细胞(hMSC)功能的支持,以及其在体内促进BMP-2 /骨髓抽吸(BMA)介导的脊柱后侧融合(PLF)的功效。测定了Reb与标准可吸收胶原海绵(ACS)的BMP-2释放动力学。利用细胞计数、荧光显微镜和MTS检测hMSC在Reb上的粘附和增殖,通过细胞碱性磷酸酶(ALP)活性检测细胞成骨分化。在活体分析中,18只Lewis大鼠在PLF手术期间接受以下治疗组:(I) Reb+BMA, (II) Reb+BMA+BMP-2和(III) BMA。使用安全、最低有效剂量的BMP-2。x线摄影和显微ct随访融合巩固3个月。牺牲后,通过手触诊、生物力学试验和组织学来确定融合率和生物力学刚度。体外,Reb与ACS的BMP-2释放动力学相似。Reb的存在增加了MSC的增殖和分化。术后3个月,融合率分别为29% (I组)、100% (II组)和0% (III组)。与i组相比,II组的生物力学刚度更高。显微ct显示II组骨体积和连通性密度增加。与II组相比,I组小梁厚度增加。H&E染色仅显示II组新骨形成。Reb具有高的蛋白结合亲和力,促进hMSC功能。BMA和最小剂量BMP-2联合使用可实现体内100%骨融合。这一数据表明,最低有效剂量的BMP-2可与瑞布联合使用。
Synthetic bone grafts are often used to achieve a well-consolidated fusion mass in spinal fusion procedures. These bone grafts function as scaffolds, and ideally support cell function and facilitate protein binding. The aim was to characterize an electrospun, synthetic bone void filler (Reb) for its bone morphogenetic protein (BMP)-2 release properties and support of human mesenchymal stem cell (hMSC) function in vitro, and its efficacy in promoting BMP-2-/bone marrow aspirate-(BMA)-mediated posterolateral spinal fusion (PLF) in vivo. BMP-2 release kinetics from Reb versus standard absorbable collagen sponge (ACS) was determined. hMSC adhesion and proliferation on Reb was tested using cell counting, fluorescence microscopy and MTS. Cell osteogenic differentiation was quantified via cellular alkaline phosphatase (ALP) activity. For in vivo analysis, 18 Lewis rats were treated during PLF surgery with the following groups: (I) Reb+BMA, (II) Reb+BMA+BMP-2 and (III) BMA. A safe, minimally effective dose of BMP-2 was used. Fusion consolidation was followed for 3 months using radiography and micro-CT. After sacrifice, fusion rate and biomechanical stiffness was determined using manual palpation, biomechanical tests and histology. In vitro, BMP-2 release kinetics were similar between Reb versus ACS. MSC proliferation and differentiation were increased in the presence of Reb. At 3 months post-surgery, fusion rates were 29% (group I), 100% (group II), and 0% (group III). Biomechanical stiffness was higher in group II versus I. Micro-CT showed an increased bone volume and connectivity density in group II. Trabecular thickness was increased in group I versus II. H&E staining showed newly formed bone in group II only. Reb possesses a high protein binding affinity and promotes hMSC function. Combination with BMA and minimal dose BMP-2 allowed for 100% bone fusion in vivo. This data suggests that a minimally effective dose of BMP-2 can be used when combined with Reb.
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