Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, The Netherlands.
Commun Biol. 2021 May 10;4(1):546. doi: 10.1038/s42003-021-02065-6.
Disturbed shear stress is thought to be the driving factor of neointimal hyperplasia in blood vessels and grafts, for example in hemodialysis conduits. Despite the common occurrence of neointimal hyperplasia, however, the mechanistic role of shear stress is unclear. This is especially problematic in the context of in situ scaffold-guided vascular regeneration, a process strongly driven by the scaffold mechanical environment. To address this issue, we herein introduce an integrated numerical-experimental approach to reconstruct the graft-host response and interrogate the mechanoregulation in dialysis grafts. Starting from patient data, we numerically analyze the biomechanics at the vein-graft anastomosis of a hemodialysis conduit. Using this biomechanical data, we show in an in vitro vascular growth model that oscillatory shear stress, in the presence of cyclic strain, favors neotissue development by reducing the secretion of remodeling markers by vascular cells and promoting the formation of a dense and disorganized collagen network. These findings identify scaffold-based shielding of cells from oscillatory shear stress as a potential handle to inhibit neointimal hyperplasia in grafts.
血流和移植物中的剪切力紊乱被认为是血管和移植物中新生内膜增生的驱动因素，例如在血液透析导管中。然而，尽管新生内膜增生很常见，但剪切力的机械作用仍不清楚。在原位支架引导的血管再生的背景下，这尤其成问题，这一过程受到支架机械环境的强烈驱动。为了解决这个问题，我们在此引入了一种综合的数值-实验方法来重建移植物-宿主反应，并研究透析移植物中的机械调节。从患者数据出发，我们对血液透析导管静脉-移植物吻合处的生物力学进行了数值分析。利用这种生物力学数据，我们在体外血管生长模型中表明，在周期性应变存在的情况下，振荡剪切力通过减少血管细胞重塑标志物的分泌和促进致密且无序的胶原网络的形成，有利于新生组织的发育。这些发现确定了基于支架的细胞免受振荡剪切力的屏蔽作为抑制移植物中新生内膜增生的潜在手段。
