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基于聚乙二醇的组织工程血管移植物的生理搏动流生物反应器调节

Physiologic pulsatile flow bioreactor conditioning of poly(ethylene glycol)-based tissue engineered vascular grafts.

作者信息

Hahn Mariah S, McHale Melissa K, Wang Eva, Schmedlen Rachael H, West Jennifer L

机构信息

Rice University, Department of Bioengineering, Houston, TX, USA.

出版信息

Ann Biomed Eng. 2007 Feb;35(2):190-200. doi: 10.1007/s10439-006-9099-3. Epub 2006 Dec 16.

DOI:10.1007/s10439-006-9099-3
PMID:17180465
Abstract

Mechanical conditioning represents a potential means to enhance the biochemical and biomechanical properties of tissue engineered vascular grafts (TEVGs). A pulsatile flow bioreactor was developed to allow shear and pulsatile stimulation of TEVGs. Physiological 120 mmHg/80 mmHg peak-to-trough pressure waveforms can be produced at both fetal and adult heart rates. Flow rates of 2 mL/sec, representative of flow through small diameter blood vessels, can be generated, resulting in a mean wall shear stress of approximately 6 dynes/cm(2) within the 3 mm ID constructs. When combined with non-thrombogenic poly(ethylene glycol) (PEG)-based hydrogels, which have tunable mechanical properties and tailorable biofunctionality, the bioreactor represents a flexible platform for exploring the impact of controlled biochemical and biomechanical stimuli on vascular graft cells. In the present study, the utility of this combined approach for improving TEVG outcome was investigated by encapsulating 10T-1/2 mouse smooth muscle progenitor cells within PEG-based hydrogels containing an adhesive ligand (RGDS) and a collagenase degradable sequence (LGPA). Constructs subjected to 7 weeks of biomechanical conditioning had significantly higher collagen levels and improved moduli relative to those grown under static conditions.

摘要

机械调节是增强组织工程血管移植物(TEVG)生化和生物力学特性的一种潜在手段。开发了一种脉动流生物反应器,以对TEVG进行剪切和脉动刺激。在胎儿和成人心率下均可产生生理状态下120 mmHg/80 mmHg的峰谷压力波形。可以产生代表通过小直径血管血流的2 mL/秒的流速,在3 mm内径的构建体中产生的平均壁面剪应力约为6达因/平方厘米。当与具有可调节机械性能和可定制生物功能的非血栓形成性聚乙二醇(PEG)基水凝胶结合使用时,该生物反应器代表了一个灵活的平台,用于探索受控生化和生物力学刺激对血管移植物细胞的影响。在本研究中,通过将10T-1/2小鼠平滑肌祖细胞封装在含有粘附配体(RGDS)和胶原酶可降解序列(LGPA)的PEG基水凝胶中,研究了这种联合方法改善TEVG结果的效用。相对于在静态条件下生长的构建体,经过7周生物力学调节的构建体具有明显更高的胶原蛋白水平和更好的模量。

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