Department of Bioengineering, Politecnico di Milano, P.za Leonardo da Vinci, 32, 20133, Milan, Italy.
Ann Biomed Eng. 2010 Jan;38(1):100-8. doi: 10.1007/s10439-009-9803-1. Epub 2009 Sep 22.
The drawbacks of state-of-the-art heart valve prostheses lead researchers to explore the prospect of using tissue-engineered constructs as possible valve substitutes. It is widely accepted that the mechanical properties of the construct are improved with mechanical stimulation during in vitro growth. We designed a new dynamic bioreactor with the perspective of using decellularized valve homografts as scaffolds in order to produce tissue-engineered valve substitutes. The design guidelines were (a) compatibility with the procedures for the treatment of homografts; (b) delivery of finely controlled pulsatile pressure loads, which induce strain stimuli that may drive cells toward repopulation of and integration with the natural scaffold; and (c) monitoring the construct's biomechanical status through a comprehensive index, i.e., its compliance. The handling needs during the set-up of the homograft and the use of the bioreactor were minimized. The bioreactor and its automated control system underwent tests with a compliant phantom valve. The estimated compliances are in good agreement with the measured ones. Tests were also carried out with porcine aortic samples in order to assess the hydrodynamic and biomechanical reliability. In the future, monitoring the construct's compliance might represent a key factor in controlling the recellularization of the valve homografts, which provides awareness of the construct's biomechanical status by real-time, non-destructive, and non-invasive means.
最先进的心脏瓣膜假体存在一些缺陷，这促使研究人员探索使用组织工程构建体作为可能的瓣膜替代物的前景。人们普遍认为，在体外生长过程中，通过机械刺激可以改善构建体的机械性能。我们设计了一种新型的动态生物反应器，使用脱细胞瓣膜同种移植物作为支架，以生产组织工程瓣膜替代物。设计指南包括：(a)与同种移植物处理程序兼容；(b)传递精细控制的脉动压力负荷，这些负荷会产生应变刺激，促使细胞重新填充并与天然支架整合；(c)通过综合指标（即顺应性）监测构建体的生物力学状态。在设置同种移植物和使用生物反应器时，尽量减少操作需求。生物反应器及其自动化控制系统已通过顺应性模拟瓣膜进行了测试。估计的顺应性与测量值吻合良好。还对猪主动脉样本进行了测试，以评估水动力和生物力学的可靠性。在未来，监测构建体的顺应性可能成为控制瓣膜同种移植物再细胞化的关键因素，通过实时、非破坏性和非侵入性的手段，可以了解构建体的生物力学状态。
