Effect of calcium phosphate cement/bone morphogenetic protein 6/vascular endothelial growth factor in bone defect repair

doi:10.3969/j.issn.2095-4344.2014.08.002

Abstract

Abstract:

BACKGROUND: Implantation of bone morphogenetic protein (BMP) or vascular endothelial growth factor (VEGF) alone, without support vectors, is easy to be flushed away by the blood flow, and thus limits the osteogenesis and angiogenesis.
OBJECTIVE: To observe the effects of combination of calcium phosphate cement (CPC), BMP-6/VEGF in bone defect repair.
METHODS: Defect models of the bilateral medial femoral condyle were prepared in New Zealand white rabbits. Then, the medial femoral condyle was filled with CPC/BMP-6/VEGF, CPC/BMP-6, and CPC, respectively, in the left side, but nothing in the right side as control. After 8 and 16 weeks of implantation, the hard tissue slices were prepared for histological observation and scanning electron microscope observation.
RESULTS AND CONCLUSION: All three kinds of materials showed good biocompatibility, and no obvious inflammation was found. After 8 weeks of implantation, the junction of the CPC/BMP-6/VEGF and bone tissue was almost completely covered by newly formed trabecular bone. With the development of cement degradation, abundant osteoblasts could be found in the surface of newborn trabecular bone. After 16 weeks of implantation, an ongoing cement degradation and bone formation was seen. Moreover, newly formed bone tissue increased and became thicker. The cement in the interface was separated into small pieces and closely interconnected with the surrounding tissues, and newly formed bone showed a mesh-like ingrowth into the cement. This newly formed bone was mature and could not be distinguished from the original trabecular bone. Both the degradation and osteogenesis of CPC and CPC/BMP-6 were much slower than that of CPC/BMP-6/VEGF (P < 0.05). This study demonstrates angiogenesis and osteogenesis in vivo through the additive effects of VEGF and BMP-6. CPC/BMP-6/VEGF can be an ideal bone substitute in bone repair.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

全文链接：

Key words: biocompatible materials, calcium phosphates, bone morphogenetic protein 6, vascular endothelial growth factors

CLC Number:

R318

Liao Hong-xing, Liu Zhan-liang, Zou Xue-nong. Effect of calcium phosphate cement/bone morphogenetic protein 6/vascular endothelial growth factor in bone defect repair[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(8): 1155-1160.

Figures/Tables 2

2.1 实验动物及大体标本分析骨水泥植入后，新西兰兔术后一般健康状况良好，未出现动物死亡情况，无术后植骨段骨折情况出现，术后伤口愈合良好，局部无红肿、窦道形成，无异常分泌物形成，除1只动物出现肢体活动障碍外，其余新西兰兔术后经过48-72 h恢复后可正常行走。 2.2 组织学观察结果见图1。术后硬组织切片光镜下观察，骨水泥填充于骨缺损部位，骨水泥无明显破裂、移位情况，与周围骨组织结合良好。各组动物在愈合过程中对骨水泥的反应无明显差异，在骨缺损部位未发现明显的炎症反应细胞。骨水泥降解程度及新骨长入情况在各时间点不断改变，并且在各组骨水泥之间存在明显差异性。植入8周：联合组骨水泥-骨组织交界处基本上被新生的骨小梁包绕，材料进一步降解，边缘部分骨水泥疏松，降解形成空隙结构并有新生骨小梁长入，将边缘部分材料分隔成小块。新生骨小梁表面可见大量活跃的成骨细胞 (图1A)；骨形态发生蛋白组于材料边缘可见少量的骨基质形成及新生骨小梁，范围较局限，骨水泥降解及新骨形成均不如联合组明显，骨小梁周边未见成骨细胞(图1C)；磷酸钙骨水泥组在材料边缘未见明显新生骨小梁形成，可见少量骨基质形成，周边磷酸钙材料密度较中央部分疏松 (图1E)；空白对照组只在骨缺损周边可见少量成骨细胞，无明显新骨形成(图1G)。植入16周：联合组可见新生骨小梁继续长入，进一步增长、增粗、增多，有大量新生编织骨成网格状长入材料中，磷酸钙材料被分隔包绕成小块。材料的降解并不局限于边缘部分，材料中央骨小梁也可见材料降解后产生的空隙。材料降解明显，但跟组织仍然紧密结合，降解与骨长入同步。此时，经过塑形后的新生骨小梁与材料相互交织在一起，形成具有承重作用的新生骨小梁 (图1B)；骨形态发生蛋白组可见新生骨小梁增多，但其数量较联合组少，骨小梁周边细胞生长活跃，新生骨与材料之间结合较为疏松，材料中央部分骨小梁长入少，材料降解较少(图1D)；磷酸钙骨水泥组仍残留大部分骨水泥，材料降解缓慢，骨小梁生长较少，范围较为局限 (图1F)。空白对照组骨缺损依然清晰存在，骨缺损壁骨化增强形成一个骨隧道，未见明显的新生骨小梁形成，髓腔内容物散落在骨缺损空腔内(图1H)，说明骨缺损并无自己愈合的能力。 2.3 扫描电镜观察结果植入8周时，联合组植入材料变疏松，骨水泥-骨组织交界处可见新生骨小梁长入，边缘部分材料疏松，降解形成空隙结构并有新生骨小梁长入 (图2A)。在联合组植入16周后，随着骨水泥进一步降解，骨水泥密度明显降低，新生骨小梁长入材料中，将骨水泥分割成小块，加速骨水泥的降解，同时新生骨小梁相互连接形成网格状与残余骨水泥牢固结合在一起，形成生物学铆定。随着骨小梁周边骨水泥的进一步降解，骨组织的进一步形成，骨小梁增长、增粗，从而取代骨水泥填充于骨缺损部位，达到骨缺损的愈合(图2B)。"

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