BMP7基因修饰的兔骨髓MSCs复合纳米羟基磷灰石/聚酰胺仿生骨修复兔下颌骨缺损的实验研究
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摘要
口腔颌面部因肿瘤、外伤造成的大面积骨缺损修复一直是口腔颌面外科领域的难题之一，目前常用的异体骨移植、自体骨移植等方法。但自体植骨来源极为有限，又增加创伤，而且不能用于修复大面积骨缺损，异体骨移植也存在来源困难，修复效果远不如内源骨，且有免疫排斥反应，可能带有潜在的病原体，例如HIV病毒、肝炎病毒等。
组织工程化骨(tissue engineered bone)研究的发展为修复大面积骨缺损提供了全新的思路和方法，在骨组织工程中，生物支架材料占据着非常重要的地位。它不仅起支撑作用，保持原有组织的形状，而且还起到模板作用，为细胞提供赖以寄宿、生长、分化和增殖的场所，从而引导受损组织的再生和控制再生组织的结构。骨组织工程的另一大要素为骨种子细胞，骨髓间充质干细胞(MSCs)很容易通过骨髓穿刺而获得，体外可迅速大量扩增，达到原来细胞数目的10～20倍，因而能够满足构建组织的细胞数量要求。更为重要的是细胞在扩增过程中能够保持干细胞的多向分化特征，在特定的环境下能够分化为成骨细胞、软骨细胞、肌腱细胞、神经细胞和脂肪细胞。因而目前MSCs是骨组织工程最常用、最理想的种子细胞，被成功地用于骨和软骨组织缺损的修复和重建。基因技术的发展，特别是将基因技术和骨组织工程相结合的基因增强的骨组织工程技术(gene enhanced bone tissue engineering)为临床促进骨缺损修复、缩短骨愈合时间带来了巨大希望。
One of the key challenges in oral and maxillofacial surgery is the treatment of bone loss because of tumor or trauma. Currently available materials for surgical replacement of the bone—such as autologous, allogenous, xenogenous grafts or artificialprosthesis—suffer from deficiencies such as donor site morbidity, limited tissue supply, immune rejection, potential transmission of pathogens.
A tissue-engineered bone from the patient's own tissue-forming cells should overcome these deficiencies. Previous reports have demonstrated the ability to form mineralized bone in vitro and in vivo on porous biodegradable polymer scaffolds. For the treatment of large bone defects, the scaffold should be a three-dimensional scaffold, thus providing tissueforming cells with a mimicked environment of the extracellular matrix; enable blood vessel ingrowth by providing the right architecture and signals for angiogenesis. The cell source is an important factor for successful tissue regeneration. Mesenchymal stem cells (MSCs) are multipotent cells can differentiate into multiple cell types present in several tissues, including bone, fat, cartilage, and muscle, and can be obtained from the same individual easily. So the MSCs is a ideal candidates for a variety of cell-based therapies.
The treatment of bone injure constitutes a major humanitarian and economic problem. An enormous expenditure will be cost during the long
组织工程化骨(tissue engineered bone)研究的发展为修复大面积骨缺损提供了全新的思路和方法，在骨组织工程中，生物支架材料占据着非常重要的地位。它不仅起支撑作用，保持原有组织的形状，而且还起到模板作用，为细胞提供赖以寄宿、生长、分化和增殖的场所，从而引导受损组织的再生和控制再生组织的结构。骨组织工程的另一大要素为骨种子细胞，骨髓间充质干细胞(MSCs)很容易通过骨髓穿刺而获得，体外可迅速大量扩增，达到原来细胞数目的10～20倍，因而能够满足构建组织的细胞数量要求。更为重要的是细胞在扩增过程中能够保持干细胞的多向分化特征，在特定的环境下能够分化为成骨细胞、软骨细胞、肌腱细胞、神经细胞和脂肪细胞。因而目前MSCs是骨组织工程最常用、最理想的种子细胞，被成功地用于骨和软骨组织缺损的修复和重建。基因技术的发展，特别是将基因技术和骨组织工程相结合的基因增强的骨组织工程技术(gene enhanced bone tissue engineering)为临床促进骨缺损修复、缩短骨愈合时间带来了巨大希望。
One of the key challenges in oral and maxillofacial surgery is the treatment of bone loss because of tumor or trauma. Currently available materials for surgical replacement of the bone—such as autologous, allogenous, xenogenous grafts or artificialprosthesis—suffer from deficiencies such as donor site morbidity, limited tissue supply, immune rejection, potential transmission of pathogens.
A tissue-engineered bone from the patient's own tissue-forming cells should overcome these deficiencies. Previous reports have demonstrated the ability to form mineralized bone in vitro and in vivo on porous biodegradable polymer scaffolds. For the treatment of large bone defects, the scaffold should be a three-dimensional scaffold, thus providing tissueforming cells with a mimicked environment of the extracellular matrix; enable blood vessel ingrowth by providing the right architecture and signals for angiogenesis. The cell source is an important factor for successful tissue regeneration. Mesenchymal stem cells (MSCs) are multipotent cells can differentiate into multiple cell types present in several tissues, including bone, fat, cartilage, and muscle, and can be obtained from the same individual easily. So the MSCs is a ideal candidates for a variety of cell-based therapies.
The treatment of bone injure constitutes a major humanitarian and economic problem. An enormous expenditure will be cost during the long
引文
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7 Jeffrey A. Fialkov, Chantal E. Holy, Molly S. Shoichet, John E. Davies. In Vivo Bone Engineering in a Rabbit Femur. THE JOURNAL OF CRANIOFACIAL SURGERY, 2003, 14(3): 324-332
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28 Jiani Chen, Shinichi Sotome, Juyong Wang, etc. Correlation of in vivo bone formation capability and in vitro differentiation ofhuman bone marrow stromal cells. J Med Dent Sci, 2005, 52(1): 27-34
29 A. Alhadlaq and J. J. Mao. Tissue-engineered Neogenesisof Human-shaped Mandibular Condyle from Rat Mesenchymal Stem Cells. J Dent Res, 2003 82(12): 950-955,
30 ADEL ALHADLAQ, JENNIFER H. ELISSEEFF, Jeremy J. Mao. Adult Stem Cell Driven Genesis of Human-Shaped Articular Condyle. Annals of Biomedical Engineering, 2004, 32(7): 911-923
31 Mark F. Pittenger, Alastair M. Mackay, Stephen C. Beck. Multilineage Potential of AdultHuman Mesenchymal Stem Cells. SCIENCE, 1999, 284(2): 143-147
32 ROY E. WEISS and A. H. REDDI. Appearance of Fibronectin during the Differentiation of Cartilage, Bone and Bone Marrow. THE JOURNAL OF CELL BIOLOGY, 1981, 88(2): 630-636
33 Jeffrey A. Fialkov, Chantal E. Holy, Molly S. Shoichet, John E. Davies. In Vivo Bone Engineering in a Rabbit Femur. THE JOURNAL OF CRANIOFACIAL SURGERY, 2003, 14 (3): 324-332
34 师昌绪．材料科学技术百科全书，北京：中国大百科全书出版社，1995，919-921．
35 顾汉卿，徐国风．生物医学材料学，天津：天津科技翻译出版社，1993，46
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