Bioreactor Cultivation of Functional Bone Grafts
Bioreactor Cultivation of Functional Bone Grafts
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DOI：
10.1007/978-1-60761-999-4_18
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发表时间：
2011-01-01
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影响因子：
--
通讯作者：
Vunjak-Novakovic, Gordana
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文献类型：
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作者：
Grayson, Warren L.;Bhumiratana, Sarindr;Vunjak-Novakovic, Gordana
临床对功能性组织工程骨移植物的需求仍然很高，以再生因创伤和手术切除先天性畸形而导致的骨缺损。一种方法是使用人间充质干细胞（hMSCs），将其植入生物材料支架中，并通过骨诱导线索诱导产生新的骨组织。由于骨细胞的高代谢活性导致营养供应的扩散限制，在常规静态条件下培养的组织结构的大小受到严重限制。为了培养临床相关尺寸的骨构建体，有必要利用灌注生物反应器，它在整个构建体体积中为细胞提供营养物质的对流转移，最关键的是氧气。本章描述了一种利用hMSCs（从骨髓抽吸液中分离出来）、生物材料支架（由完全去细胞化的牛小梁骨制成）和灌注生物反应器（设计用于同时培养6个构建体长达5周）构建4毫米厚圆柱形骨移植物的方法。这种方法的结果是形成完全可行的、临床相关大小的生物骨移植物。
The clinical demand for functional tissue-engineered bone grafts to regenerate bone defects resulting from trauma and surgical resection of congenital anomalies remains very high. One approach involves the use of human mesenchymal stem cells (hMSCs) that are seeded into biomaterial scaffolds and are induced to generate new bone tissue by osteo-inductive cues. The size of tissue constructs that can be cultured tinder conventional static conditions is seriously limited by diffusional constraints of nutrient supply resulting from high metabolic activity of bone cells. To cultivate bone constructs of clinically-relevant sizes, it is necessary to utilize perfusion bioreactors, which provides convective transfer of nutrients, and most critically oxygen, to the cells throughout the construct volume. This chapter describes a method for engineering 4-mm thick cylindrical bone grafts using hMSCs (isolated from bone marrow aspirates), biomaterial scaffolds (made of fully decellularized bovine trabecular bone), and a perfusion bioreactor (designed tor simultaneous cultivation of six constructs for up to 5 weeks). This approach results in the formation of completely viable, biological bone grafts of clinically relevant sizes.