Department of Biomedical Engineering, Yale University, New Haven, CT, 06520, USA.
Center for Regenerative Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Ann Biomed Eng. 2018 Nov;46(11):1938-1950. doi: 10.1007/s10439-018-2086-7. Epub 2018 Jul 9.
In vivo development of a neovessel from an implanted biodegradable polymeric scaffold depends on a delicate balance between polymer degradation and native matrix deposition. Studies in mice suggest that this balance is dictated by immuno-driven and mechanotransduction-mediated processes, with neotissue increasingly balancing the hemodynamically induced loads as the polymer degrades. Computational models of neovessel development can help delineate relative time-dependent contributions of the immunobiological and mechanobiological processes that determine graft success or failure. In this paper, we compare computational results informed by long-term studies of neovessel development in immuno-compromised and immuno-competent mice. Simulations suggest that an early exuberant inflammatory response can limit subsequent mechano-sensing by synthetic intramural cells and thereby attenuate the desired long-term mechano-mediated production of matrix. Simulations also highlight key inflammatory differences in the two mouse models, which allow grafts in the immuno-compromised mouse to better match the biomechanical properties of the native vessel. Finally, the predicted inflammatory time courses revealed critical periods of graft remodeling. We submit that computational modeling can help uncover mechanisms of observed neovessel development and improve the design of the scaffold or its clinical use.
植入可生物降解聚合物支架后的新生血管的体内发育取决于聚合物降解和天然基质沉积之间的微妙平衡。在小鼠中的研究表明，这种平衡是由免疫驱动和力学转导介导的过程决定的，随着聚合物的降解，新生组织逐渐平衡血流动力学诱导的负荷。新生血管发育的计算模型可以帮助描绘决定移植物成功或失败的免疫生物学和力学生物学过程的相对时变贡献。在本文中，我们比较了基于免疫缺陷和免疫功能正常小鼠的新生血管发育的长期研究的计算结果。模拟表明，早期过度的炎症反应可能会限制合成壁内细胞的后续力学感应，从而减弱对所需的长期力学介导的基质产生的影响。模拟还突出了两种小鼠模型之间的关键炎症差异，这使得免疫缺陷小鼠中的移植物能够更好地匹配天然血管的生物力学特性。最后，预测的炎症时间过程揭示了移植物重塑的关键时期。我们认为，计算建模可以帮助揭示观察到的新生血管发育的机制，并改进支架的设计或其临床应用。
