1 Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
2 IZKF Research Group for Experimental Stem Cell Transplantation Medical Clinic and Policlinic II, Center for Experimental Molecular Medicine (ZEMM), University Clinic of Würzburg , Würzburg, Germany .
Tissue Eng Part A. 2018 Mar;24(5-6):479-492. doi: 10.1089/ten.TEA.2017.0110. Epub 2017 Oct 25.
Axial vascularization represents a mandatory requirement for clinically applied larger scale vascularized bone grafts. The aim of this study was to combine the arteriovenous (AV) loop model in the rat with a critically sized femoral bone defect and to successfully transplant axially vascularized bone constructs into the defect.
In Groups A and C, an AV loop together with a clinically approved hydroxyapatite and beta-tricalcium phosphate (HA/β-TCP) matrix, mesenchymal stem cells, and recombinant human bone morphogenetic protein 2 were implanted into a newly designed porous titanium chamber with an integrated osteosynthesis plate in the thighs of rats, whereas in Groups B and D, the same matrix composition without AV loop and, in Group E, only the HA/β-TCP matrix were implanted. After 6 weeks, the constructs were transplanted into a 10 mm femoral defect created in the same leg, in Groups A and C, under preservation of the AV loop pedicle. Group F served as a control group with an empty chamber. Ten days (Groups A and B) and 12 weeks (Groups C-F) after transplantation, the femora together with the constructs were explanted and investigated using computed tomography (CT), micro-CT, X-ray, histology, and real-time polymerase chain reaction (RT-PCR).
Ten days after transplantation, Group A showed a maintained vascular supply leading to increased vascularization, cell survival in the scaffold center, and bone generation compared to Group B. After 12 weeks, there was no difference detectable among all groups regarding total vessel number, although Group C, using the AV loop, still showed increased vascularization of the construct center compared to Groups D and E. In Group C, there was still enhanced bone generation detectable compared to the other groups and increased bony fusion rate at the proximal femoral stump.
This study shows the combination of the AV loop model in the rat with a critically sized femoral defect. By maintenance of the vascular supply, the constructs initially showed increased vascularization, leading to increased bone formation and bony fusion in the long term.
轴向血管化是临床应用较大规模血管化骨移植物的必要条件。本研究旨在将大鼠的动静脉(AV)环模型与临界大小的股骨骨缺损相结合,并成功将轴向血管化骨构建体移植到缺损部位。
在 A 组和 C 组中,将 AV 环与临床认可的羟磷灰石和β-磷酸三钙(HA/β-TCP)基质、间充质干细胞和重组人骨形态发生蛋白 2 一起植入大鼠大腿中带有集成骨内固定板的新型多孔钛室中,而在 B 组和 D 组中,使用相同的基质成分但没有 AV 环,在 E 组中仅植入 HA/β-TCP 基质。6 周后,在保留 AV 环蒂的情况下,将构建体移植到同一腿中创建的 10mm 股骨缺损中,在 A 组和 C 组中。F 组作为对照组,采用空室。移植后 10 天(A 组和 B 组)和 12 周(C 组-F 组),取出股骨和构建体,使用计算机断层扫描(CT)、微 CT、X 射线、组织学和实时聚合酶链反应(RT-PCR)进行研究。
移植后 10 天,A 组显示维持的血管供应导致血管化增加、支架中心细胞存活和骨生成增加,与 B 组相比。12 周后,所有组之间的总血管数均无差异,尽管使用 AV 环的 C 组与 D 组和 E 组相比,构建体中心的血管化仍有所增加。与其他组相比,C 组仍可检测到增强的骨生成,并且在股骨近端残端处的骨融合率增加。
本研究展示了大鼠动静脉环模型与临界大小股骨缺损的结合。通过维持血管供应,构建体最初显示出增加的血管化,从而在长期内增加骨生成和骨融合。