Enabling tools for engineering collagenous tissues integrating bioreactors, intravital imaging, and biomechanical modeling
Enabling tools for engineering collagenous tissues integrating bioreactors, intravital imaging, and biomechanical modeling
复制标题
DOI：
10.1073/pnas.0907813106
复制
发表时间：
2010-02-23
影响因子：
11.1
通讯作者：
Humphrey, Jay D.
中科院分区：
文献类型：
--
作者：
Niklason, Laura E.;Yeh, Alvin T.;Humphrey, Jay D.
许多研究人员已经设计了具有良好机械性能的各种结缔组织，但很少有工具能够全面了解胶原纤维的相关形成，这是结缔组织硬度的主要决定因素。为此，我们开发了一个生物力学模型的聚合物支架上生长的胶原组织，占聚合物降解的动力学，以及响应于在生物反应器中赋予的循环应变的多个家族的胶原纤维的合成和降解。该模型对培养8周的管状工程血管的总体厚度和应力-拉伸关系预测良好，并表明尚未达到稳定状态。为了促进模型的未来改进，我们还开发了生物反应器，使活体非线性光学显微镜成像。使用这些工具，我们发现，胶原纤维排列强烈驱动的非降解聚合物纤维在培养过程中的早期，与随后的机械刺激分散的纤维取向的聚合物纤维降解。总之，在聚合物支架上培养的工程组织的生长和重塑的数学模型可以预测长期培养后不断变化的组织形态和力学，相关的经验观察有望进一步加深我们对体外胶原基质发育的理解。
Many investigators have engineered diverse connective tissues having good mechanical properties, yet few tools enable a global understanding of the associated formation of collagen fibers, the primary determinant of connective tissue stiffness. Toward this end, we developed a biomechanical model for collagenous tissues grown on polymer scaffolds that accounts for the kinetics of polymer degradation as well as the synthesis and degradation of multiple families of collagen fibers in response to cyclic strains imparted in a bioreactor. The model predicted well both overall thickness and stress-stretch relationships for tubular engineered vessels cultured for 8 weeks, and suggested that a steady state had not yet been reached. To facilitate future refinements of the model, we also developed bioreactors that enable intravital nonlinear optical microscopic imaging. Using these tools, we found that collagen fiber alignment was driven strongly by nondegraded polymer fibers at early times during culture, with subsequent mechano-stimulated dispersal of fiber orientations as polymer fibers degraded. In summary, mathematical models of growth and remodeling of engineered tissues cultured on polymeric scaffolds can predict evolving tissue morphology and mechanics after long periods of culture, and related empirical observations promise to further our understanding of collagen matrix development in vitro.