Lampert Florian M, Momeni Arash, Filev Filip, Torio-Padron Nestor, Finkenzeller Günter, Stark G Björn, Steiner Dominik, Koulaxouzidis Georgios
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Hugstetterstr. 55, D-79106, Freiburg, Germany.
Division of Plastic and Reconstructive Surgery, Stanford University Medical Center, 770 Welch Road, Suite 400, Palo Alto, CA, 94304-5715, USA.
J Orthop Surg Res. 2015 Apr 29;10:55. doi: 10.1186/s13018-015-0196-6.
We developed an experimental rat model to explore the possibility of enhancing the healing of critical-size bone defects. The aim of this study was to demonstrate the feasibility of this concept by achieving high local BMP-2 expression via a transduced muscle flap that would facilitate bony union while minimizing systemic sequelae.
The transduction potential of the adenoviral vector encoding for BMP-2 was tested in different cell lines in vitro. In vivo experiments consisted of harvesting a pedicled quadriceps femoris muscle flap with subsequent creation of a critical-size defect in the left femur in Sprague-Dawley rats. Next, the pedicled muscle flap was perfused with high titers of Ad.BMP-2 and Ad.GFP virus, respectively. Twelve animals were divided into three groups comparing the effects of Ad.BMP-2 transduction to Ad.GFP and placebo. Bone healing was monitored radiologically with subsequent histological analysis post-mortem.
The feasibility of this concept was demonstrated by successful transduction in vitro and in vivo as evidenced by a marked increase of BMP-2 expression. The three examined groups only showed minor difference regarding bone regeneration; however, one complete bridging of the defect was observed in the Ad.BMP-2 group. No evidence of systemic viral contamination was noted.
A marked increase of local BMP-2 expression (without untoward systemic sequelae) was detected. However, bone healing was not found to be significantly enhanced, possibly due to the small sample size of the study.
我们建立了一个实验性大鼠模型，以探索促进临界尺寸骨缺损愈合的可能性。本研究的目的是通过转导肌瓣实现局部高BMP - 2表达来证明这一概念的可行性，这将促进骨愈合同时将全身后遗症降至最低。
在体外不同细胞系中测试编码BMP - 2的腺病毒载体的转导潜力。体内实验包括获取带蒂股四头肌肌瓣，随后在Sprague - Dawley大鼠的左股骨中制造临界尺寸缺损。接下来，分别用高滴度的Ad.BMP - 2和Ad.GFP病毒灌注带蒂肌瓣。将12只动物分为三组，比较Ad.BMP - 2转导与Ad.GFP和安慰剂的效果。通过放射学监测骨愈合情况，随后进行死后组织学分析。
体外和体内成功转导证明了这一概念的可行性，BMP - 2表达显著增加。三个检测组在骨再生方面仅显示出微小差异；然而，在Ad.BMP - 2组中观察到一例缺损完全桥接。未发现全身病毒污染的证据。
检测到局部BMP - 2表达显著增加（无不良全身后遗症）。然而，未发现骨愈合得到显著增强，可能是由于研究样本量较小。
