组织工程心脏瓣膜生物反应器的改建及初步应用
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全军医药科研"十五 "规划重点课题(01Z060).


Modification of bioreactor for tissue-engineered heart valve and its application
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Supported by Key Medical Program of the l0th Five-Year Plan of PLA(01Z060).

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    摘要:

    目的:对自主研制脉动生物反应器加以改进,使其脉动流场能够体外模拟高流量高压力的在体瓣膜环境,并对整体构建的组织工程心脏瓣膜(TEHV)进行流场内培养的初步研究.方法:采用韩国产双囊搏动泵(T-PLS)作为新脉动流场的动力装置,并设计了新的气液交换通路以减少污染.以脱细胞猪主动脉瓣为支架,人的骨髓间质干细胞(BMSCs)为种子细胞整体构建TEHV.静态培养4 d后,置于生物反应器内分别在小流量(0~600 ml/min)和大流量(0~4 800 ml/min)脉动流场培养7 d,观察细胞残留情况.结果:流场改进后流量范围从0~1 200 ml/min提高到0~6 000 ml/min,系统内压力范围从0~40 mmHg(1 mmHg=0.133 kPa)提高到0~180 mmHg.TEHV在低流量脉动流场内有部分细胞存留(26.3﹪),而在大流量流场中细胞几无存留.结论:新的生物反应器能够基本模拟在体瓣膜的流体动力学环境,能够应用于TEHV的体外培育研究,但目前构建的TEHV尚不能耐受大流量流体的冲击.

    Abstract:

    Objective: To modify the pulsatile bioreactor we constructed previously for simulating the high-flow, highpressure hemodynamics of heart valve in vivo, and to experimentally cultivate the tissue-engineered heart valves (TEHV) in the modified bioreactor. Methods: T-PLS system (NewheartBio Co. ,Ltd Korea) was used to generate pulsatile flow in the modified bioreactor and we designed a new air-exchange pathway to avoid contamination. The TEHV were made by seeding human bone mesenchymal stem cells (BMSCs) on deellularized porcine heart valve. After cultured under static condition for 4 d, the TEHVs were moved to the modified bioreactor and exposed to low-flow (0-600 ml/min) or high-flow(0-4 800 ml/min) pulsatile hydrodynamics for 7d, then the cells on TEHVs were evaluated. Results: After modification, the flow range expanded from (0- 1 200) ml/min to (0-6 000) ml/min and the pressure range expanded from (0-40) mmHg to (0-180) mmHg. In culture experiments, 26.3 % of the seeded cells remained under low-flow environment and cells were completely lost under the high-flow dynamics. Conclusion: The modified bioreactor can basically simulate the dynamics of heart valve in vivo and can be used in TEHV cultivation research. However, the current TEHV can not tolerate the high-flow pulsatile hydrodynamics

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  • 收稿日期:2006-06-03
  • 最后修改日期:2006-12-14
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  • 在线发布日期: 2007-01-20
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