Geiger F, Lorenz H, Xu W, Szalay K, Kasten P, Claes L, Augat P, Richter W
Division of Experimental Orthopaedics, Orthopaedic University Hospital of Heidelberg, Schlierbacher Landstr. 200a, 69118 Heidelberg, Germany.
Bone. 2007 Oct;41(4):516-22. doi: 10.1016/j.bone.2007.06.018. Epub 2007 Jul 6.
Bone graft substitutes often exhibit poor bone regeneration in large defects because of inadequate vascularization. Studies have shown that if blood supply is compromised, application of osteogenic factors alone could not induce successful healing. This study was to evaluate the effects of vascular endothelial growth factor, which combined with a coralline scaffold, on vascularization, scaffold resorption and osteogenesis in a rabbit radius critical size defect model. The scaffold was either coated with a control-plasmid DNA (group 1), coated with VEGF-plasmid DNA (group 2), loaded with mesenchymal stem cells (BMSC) transfected with control plasmid (group 3) or with both stem cells and the VEGF plasmid (group 4). X-rays were taken every 4 weeks up to week 16, when animals were euthanized. The volume of new bone was measured by mu-CT scans and blood vessels were counted after anti-CD31 staining of endothelial cells. The results from the solitary VEGF- and VEGF-transfected cells (groups 2 and 4) demonstrated significantly enhanced vascularization, osteogenesis and resorption of the carrier when compared to the control group. The highest degree of osteogenesis was found when the carrier was loaded with BMSC (group 3), whereas VEGF-transfected cells led to the highest vascularization and fastest resorption of the bone substitute. Additionally, VEGF-transfected BMSC led to a more homogenous vascularization of the defect. The results indicate that VEGF can be a helpful factor to improve healing in large bone defects, in which bone substitutes will otherwise not be vascularized and replaced by fresh bone.
由于血管化不足，骨移植替代物在大的骨缺损中常常表现出较差的骨再生能力。研究表明，如果血液供应受到损害，仅应用成骨因子并不能诱导成功愈合。本研究旨在评估血管内皮生长因子与珊瑚支架联合应用对兔桡骨临界尺寸缺损模型中血管化、支架吸收和骨生成的影响。支架分别用对照质粒DNA包被（第1组）、用VEGF质粒DNA包被（第2组）、负载转染对照质粒的间充质干细胞（BMSC）（第3组）或同时负载干细胞和VEGF质粒（第4组）。在第16周动物安乐死之前，每4周进行一次X线检查。通过微计算机断层扫描（μ-CT）测量新骨体积，并在内皮细胞进行抗CD31染色后计数血管。与对照组相比，单独使用VEGF和转染VEGF的细胞（第2组和第4组）的结果显示，载体的血管化、骨生成和吸收均显著增强。当载体负载BMSC时（第3组），骨生成程度最高，而转染VEGF的细胞导致骨替代物的血管化程度最高且吸收最快。此外，转染VEGF的BMSC使缺损处的血管化更加均匀。结果表明，VEGF可能是改善大骨缺损愈合的一个有益因素，在大骨缺损中，否则骨替代物将无法血管化并被新鲜骨替代。
