Bioreactor-based bone tissue engineering: The influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization

Bioreactor-based bone tissue engineering: The influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization
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DOI:
10.1073/pnas.0402532101
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发表时间:
2004-08-03
影响因子:
11.1
通讯作者:
Laurencin, CT
Laurencin, CT
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yu, XJ;Botchwey, EA;Laurencin, CT

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组织工程中的一个重要问题是由于营养输送不足,组织工程构建物中组织向内生长受限的可能性。我们报道了一种使用高纵横比旋转生物反应器和三维支架的动态流动培养系统,用于培养大鼠颅骨成骨细胞。31)通过混合85:15的聚(丙交酯-共-乙交酯)的轻于水(密度,<1g/ml)和重于水(密度,> 1g/ml)的微球来设计支架。我们通过使用粒子跟踪系统量化了通过支架的3D流的速率,结果表明,运动轨迹,因此,在旋转生物反应器中的支架周围和通过支架的流速可以通过改变比水轻的比水轻的微球的比例来操纵。当大鼠原代颅骨细胞在生物反应器中的支架上培养7天时,与静态条件相比,3D动态流动环境影响骨细胞分布并增强组织工程构建体内的细胞表型表达和矿化基质合成。这些研究为探索动态流动对成骨细胞功能的影响提供了基础,并为体外骨组织工程生物反应器中适用的3D支架的设计和优化提供了重要的见解。
An important issue in tissue engineering concerns the possibility of limited tissue ingrowth in tissue-engineered constructs because of insufficient nutrient transport. We report a dynamic flow culture system using high-aspect-ratio vessel rotating bioreactors and 3D scaffolds for culturing rat calvarial osteoblast cells. 31) scaffolds were designed by mixing lighter-than-water (density, < 1 g/ml) and heavier-than-water (density, > 1 g/ml) microspheres of 85:15 poly(lactide-co-glycolide). We quantified the rate of 3D flow through the scaffolds by using a particle-tracking system, and the results suggest that motion trajectories and, therefore, the flow velocity around and through scaffolds in rotating bioreactors can be manipulated by varying the ratio of heavier-than-water to lighter-than-water microspheres. When rat primary calvarial cells were cultured on the scaffolds in bioreactors for 7 days, the 3D dynamic flow environment affected bone cell distribution and enhanced cell phenotypic expression and mineralized matrix synthesis within tissue-engineered constructs compared with static conditions. These studies provide a foundation for exploring the effects of dynamic flow on osteoblast function and provide important insight into the design and optimization of 3D scaffolds suitable in bioreactors for in vitro tissue engineering of bone.