Estimation of Aortic Valve Interstitial Cell-Induced 3D Remodeling of Poly(Ethylene Glycol) Hydrogel Environments Using an Inverse Finite Element Approach

作     者：Khang, Alex Steinman, John Tuscher, Robin Feng, Xinzeng Sacks, Michael S. 

作者机构：James T. Willerson Center for Cardiovascular Modeling and Simulation Oden Institute for Computational Engineering and Sciences The Department of Biomedical Engineering The University of Texas at Austin 201 East 24th St Stop C0200 AustinTX78712-1229 United States 

出 版 物：《SSRN》 

年 卷 期：2022年

核心收录：

主　　题：Tissue 

摘      要：Aortic valve interstitial cells (AVICs) reside within the leaflet tissues of the aortic valve and function to replenish, restore, and remodel extracellular matrix components. AVIC contractility is brought about through the contractile properties of the underlying stress fibers and plays a crucial role in processes such as wound healing and mechanotransduction. Currently, it is technically challenging to directly investigate AVIC contractile behaviors within the dense leaflet tissues. As a result, optically clear poly (ethylene glycol) (PEG) hydrogel matrices have been used to study AVIC contractility through means of 3D traction force microscopy (3DTFM). However, the stiffness of the hydrogel material within the vicinity of the AVIC is difficult to measure directly and is further confounded by the remodeling activity of the AVIC. Ambiguity in the local hydrogel mechanical properties can lead to large errors in computed cellular tractions. Herein, we developed an inverse computational approach to estimate AVIC-induced remodeling of the hydrogel material. The capabilities of the model were validated with a ground truth data set generated via a test problem comprised of an experimentally measured AVIC geometry and a prescribed modulus field containing unmodified, stiffened, and degraded regions. The inverse model was able to estimate the ground truth data set with high accuracy. When applied to AVICs assessed via 3DTFM, the model estimated regions of significant stiffening and degradation local to the AVIC. We observed that stiffening was largely localized at AVIC protrusions and was likely a result of collagen deposition as confirmed by immunostaining for collagen type 1. Degradation was more spatially uniform and present in regions further away from the AVIC surface and likely a result of enzymatic activity. Our results indicate that AVICs substantially modify the local hydrogel mechanics, which were successfully quantified by our computational model. Looking forward