静电纺丝合成骨空隙填充剂促进人 MSC 功能和 BMP-2 介导的脊柱融合。
Electrospun, synthetic bone void filler promotes human MSC function and BMP-2 mediated spinal fusion.
机构信息
Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
出版信息
J Biomater Appl. 2020 Oct-Nov;35(4-5):532-543. doi: 10.1177/0885328220937999. Epub 2020 Jul 5.
INTRODUCTION
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.
OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
简介
在脊柱融合手术中，合成骨移植物常被用于获得牢固的融合块。这些骨移植物作为支架，理想情况下支持细胞功能并促进蛋白质结合。
目的
本研究旨在对一种电纺合成骨空洞填充剂（Reb）的骨形态发生蛋白（BMP）-2释放特性及其对人骨髓间充质干细胞（hMSC）体外功能的支持作用进行研究，并评估其在体内促进 BMP-2/骨髓抽吸物（BMA）介导的后路脊柱融合（PLF）的疗效。
方法
测定 Reb 与标准可吸收胶原海绵（ACS）的 BMP-2释放动力学。采用细胞计数、荧光显微镜和 MTS 法检测 Reb 上 hMSC 的黏附和增殖。通过细胞碱性磷酸酶（ALP）活性定量检测细胞成骨分化。在体内分析中，18 只 Lewis 大鼠在 PLF 手术中接受以下治疗组：（I）Reb+BMA，（II）Reb+BMA+BMP-2，和（III）BMA。使用安全的、最小有效剂量的 BMP-2。使用放射学和 micro-CT 对 3 个月的融合固定情况进行随访。处死动物后，通过手动触诊、生物力学试验和组织学确定融合率和生物力学刚度。
结果
在体外，Reb 与 ACS 相比，BMP-2 释放动力学相似。Reb 存在时，MSC 增殖和分化增加。术后 3 个月，融合率分别为 29%（组 I）、100%（组 II）和 0%（组 III）。组 II 的生物力学刚度高于组 I。micro-CT 显示组 II 的骨体积和连通密度增加。组 I 的骨小梁厚度高于组 II。H&E 染色仅在组 II 中显示出新生骨。
结论
Reb 具有较高的蛋白结合亲和力，并能促进 hMSC 功能。与 BMA 和最小剂量 BMP-2 联合使用可在体内实现 100%骨融合。这些数据表明，当与 Reb 联合使用时，可使用最小有效剂量的 BMP-2。
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