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局部递送抗坏血酸和β-甘油磷酸增强小鼠双节段后路脊柱融合模型中的局部骨移植。

Locally Delivered Ascorbic Acid and β-Glycerophosphate Augment Local Bone Graft in a Murine Model of 2-Level Posterior Spinal Fusion.

作者信息

Chen Joshua Vic, Lee Katie, Tillinghast Kyle, Halloran Bernard, Dang Alan B C

机构信息

Department of Orthopaedic Surgery, University of California, San Francisco, California.

Orthopaedic Section, Department of Surgery, San Francisco VA Health Center, San Francisco, California.

出版信息

Int J Spine Surg. 2021 Oct;15(5):921-928. doi: 10.14444/8120. Epub 2021 Oct 14.

Abstract

BACKGROUND

Ascorbic acid is involved in collagen biosynthesis and upregulates alkaline phosphatase, potentially alleviating cell senescence and stimulating mesenchymal stem cell proliferation and differentiation into osteoblasts. We hypothesized locally delivered ascorbic acid and β-glycerophosphate act as a bone graft extender to increase the volume of new bone formed in a murine model of posterior lumbar fusion.

METHODS

Collagen sponges were used as delivery vehicles. Sponges were prepared with primary media alone or with the addition of ascorbic acid and β-glycerophosphate. Fresh morselized bone graft from 12 donor mice was used. Twenty-four healthy male C57BL/6 mice underwent an uninstrumented posterior L3-L5 lumbar fusion. One control group received morselized bone only. A second "sponge control" group received morselized bone with the control collagen sponge. The third group received morselized bone and a collagen sponge with ascorbic acid and β-glycerophosphate. Three months postoperatively, the lumbar spine underwent high-resolution micro-computed tomography for analysis of bone formation, density, and bridging fusion.

RESULTS

Animals receiving ascorbic acid and β-glycerophosphate had a statistically significant increase in corrected bone volume compared with control and sponge groups, with a 56.3% and 25.4% increase, respectively. Mineralized bone fraction was statistically significantly decreased for animals in the ascorbic acid group compared with control and sponge groups. There was no significant difference in fusion rate between test groups.

CONCLUSIONS

Locally delivered ascorbic acid and β-glycerophosphate in a murine model of posterior spinal fusion yielded statistically significant increases in new bone formation in the lumbar spine but statistically significant decreases in mineralized bone fraction. Differences in fusion rate were not statistically significant.

CLINICAL RELEVANCE

This study provides early data suggesting that delivery of ascorbic acid to a spinal fusion site may be beneficial but does not yet establish an indication for clinical use. Further studies are needed to determine optimal dose and delivery of ascorbic acid.

摘要

背景

抗坏血酸参与胶原蛋白的生物合成,并上调碱性磷酸酶,可能减轻细胞衰老,刺激间充质干细胞增殖并分化为成骨细胞。我们假设局部递送抗坏血酸和β-甘油磷酸酯可作为骨移植增强剂,以增加小鼠后腰椎融合模型中形成的新骨体积。

方法

使用胶原海绵作为递送载体。海绵分别用单纯基础培养基或添加抗坏血酸和β-甘油磷酸酯制备。使用来自12只供体小鼠的新鲜碎骨移植。24只健康雄性C57BL/6小鼠接受了非器械辅助的L3-L5后腰椎融合术。一个对照组仅接受碎骨移植。第二个“海绵对照组”接受碎骨移植和对照胶原海绵。第三组接受碎骨移植以及含有抗坏血酸和β-甘油磷酸酯的胶原海绵。术后三个月,对腰椎进行高分辨率微计算机断层扫描,以分析骨形成、密度和桥接融合情况。

结果

与对照组和海绵组相比,接受抗坏血酸和β-甘油磷酸酯的动物校正骨体积有统计学显著增加,分别增加了56.3%和25.4%。与对照组和海绵组相比,抗坏血酸组动物的矿化骨分数有统计学显著降低。试验组之间的融合率无显著差异。

结论

在小鼠后脊柱融合模型中局部递送抗坏血酸和β-甘油磷酸酯使腰椎新骨形成有统计学显著增加,但矿化骨分数有统计学显著降低。融合率差异无统计学显著意义。

临床意义

本研究提供的早期数据表明,向脊柱融合部位递送抗坏血酸可能有益,但尚未确立临床应用指征。需要进一步研究以确定抗坏血酸的最佳剂量和递送方式。

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