Health Sciences and Technology Program, Harvard University - Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sci Robot. 2024 Jun 12;9(91):eadj9769. doi: 10.1126/scirobotics.adj9769.
Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to enable control over both disease progression and reversal, hindering their clinical relevance. Here, we describe a method for progressive and reversible aortic banding based on an implantable expandable actuator that can be finely tuned to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our platform can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leveraged soft robotics to enable noninvasive aortic debanding, demonstrating that these changes can be partly reversed because of cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this animal model could elucidate fundamental mechanisms of cardiac remodeling and optimize timing of intervention for pressure overload.
我们对左心室压力超负荷导致的心脏重构过程的理解主要来自于主动脉缩窄的动物模型。然而,这些研究无法同时控制疾病的进展和逆转,从而降低了它们的临床相关性。在这里,我们描述了一种基于可植入式可膨胀执行器的渐进式和可逆性主动脉缩窄方法,该方法可以精细地调节主动脉缩窄和去缩窄,从而在大鼠模型中进行调节。通过导管插入术、成像和组织学研究,我们证明我们的平台可以以可控的方式再现与压力超负荷相关的血流动力学和结构变化。我们利用软机器人实现了非侵入性的主动脉去缩窄,证明由于停止生物力学刺激,这些变化可以部分逆转。通过再现纵向疾病进展和可逆性,这种动物模型可以阐明心脏重构的基本机制,并优化压力超负荷干预的时机。