A single topical dose of erythropoietin applied on a collagen carrier enhances calvarial bone healing in pigs.

A single topical dose of erythropoietin applied on a collagen carrier enhances calvarial bone healing in pigs.
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DOI:
10.3109/17453674.2014.889981
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发表时间:
2014-04
期刊:
影响因子:
3.7
通讯作者:
Bünger C
Bünger C
中科院分区:
医学2区
文献类型:
--
作者:
Rölfing JH;Jensen J;Jensen JN;Greve AS;Lysdahl H;Chen M;Rejnmark L;Bünger C

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促红细胞生成素(EPO)的成骨效力已被证实。然而,其在大型动物模型中的有效性尚未得到研究;也没有临床安全剂量。本研究的目的是克服以往研究的这些局限性,从而为可能的临床应用铺平道路。我们的假设是,与生理盐水对照相比,EPO增加了同一受试者的颅骨骨愈合。我们使用了猪颅骨缺损模型。在18头猪中,每头猪钻6个圆柱形缺陷(直径:1厘米,高度:1厘米),进行3次两两比较。治疗包括900 IU/mL EPO或等体积生理盐水联合自体移植物、胶原载体或聚己内酯(PCL)支架。观察5周后,通过高分辨率定量计算机断层扫描评估主要结果(骨体积分数(BV/TV))。次要结果测量是组织形态测量和血液样本。与盐水处理的胶原相比,epo处理组的中位BV/TV比值为1.06 (CI: 1.02-1.11)。组织形态测量显示相似的中位效应大小,但没有达到统计学意义。自体移植物治疗具有良好的愈合潜力,能够独立于EPO治疗完全再生骨缺损。骨长入PCL支架稀疏,无论是否有EPO。没有观察到实质性的全身效应或不良事件。epo处理的缺损与盐水处理的缺损血管数目相似。外用促生成素在胶原载体上适度增加骨愈合。该给药方案是安全的,并有可能在临床环境中应用。然而,为了增加临床相关性,应该研究一种更有效但临床安全的剂量。
The osteogenic potency of erythropoietin (EPO) has been documented. However, its efficacy in a large-animal model has not yet been investigated; nor has a clinically safe dosage. The purpose of this study was to overcome such limitations of previous studies and thereby pave the way for possible clinical application. Our hypothesis was that EPO increases calvarial bone healing compared to a saline control in the same subject. We used a porcine calvarial defect model. In each of 18 pigs, 6 cylindrical defects (diameter: 1 cm; height: 1 cm) were drilled, allowing 3 pairwise comparisons. Treatment consisted of either 900 IU/mL EPO or an equal volume of saline in combination with either autograft, a collagen carrier, or a polycaprolactone (PCL) scaffold. After an observation time of 5 weeks, the primary outcome (bone volume fraction (BV/TV)) was assessed with high-resolution quantitative computed tomography. Secondary outcome measures were histomorphometry and blood samples. The median BV/TV ratio of the EPO-treated collagen group was 1.06 (CI: 1.02–1.11) relative to the saline-treated collagen group. Histomorphometry showed a similar median effect size, but it did not reach statistical significance. Autograft treatment had excellent healing potential and was able to completely regenerate the bone defect independently of EPO treatment. Bony ingrowth into the PCL scaffold was sparse, both with and without EPO. Neither a substantial systemic effect nor adverse events were observed. The number of blood vessels was similar in EPO-treated defects and saline-treated defects. Topical administration of EPO on a collagen carrier moderately increased bone healing. The dosing regime was safe, and could have possible application in the clinical setting. However, in order to increase the clinical relevance, a more potent but still clinically safe dose should be investigated.
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DOI: 10.1371/journal.pone.0010853
发表时间: 2010-05-27
期刊: PloS one
影响因子: 3.7
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DOI: 10.1016/j.bone.2011.08.004
发表时间: 2011-11-01
期刊: BONE
影响因子: 4.1
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