Zhang Will, Ayoub Salma, Liao Jun, Sacks Michael S
Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Tissue Bioengineering Laboratory, Department of Ag. and Bio. Engineering, Bagley College of Engineering, College of Agriculture and Life Sciences, Mississippi State University, MS, USA.
Acta Biomater. 2016 Mar 1;32:238-255. doi: 10.1016/j.actbio.2015.12.001. Epub 2015 Dec 19.
Fundamental to developing a deeper understanding of pathophysiological remodeling in mitral valve (MV) disease is the development of an accurate tissue-level constitutive model. In the present work, we developed a novel meso-scale (i.e. at the level of the fiber, 10-100 μm in length scale) structural constitutive model (MSSCM) for MV leaflet tissues. Due to its four-layer structure, we focused on the contributions from the distinct collagen and elastin fiber networks within each tissue layer. Requisite collagen and elastin fibrous structural information for each layer were quantified using second harmonic generation microscopy and conventional histology. A comprehensive mechanical dataset was also used to guide model formulation and parameter estimation. Furthermore, novel to tissue-level structural constitutive modeling approaches, we allowed the collagen fiber recruitment function to vary with orientation. Results indicated that the MSSCM predicted a surprisingly consistent mean effective collagen fiber modulus of 162.72 MPa, and demonstrated excellent predictive capability for extra-physiological loading regimes. There were also anterior-posterior leaflet-specific differences, such as tighter collagen and elastin fiber orientation distributions (ODF) in the anterior leaflet, and a thicker and stiffer atrialis in the posterior leaflet. While a degree of angular variance was observed, the tight valvular tissue ODF also left little room for any physically meaningful angular variance in fiber mechanical responses. Finally, a novel fibril-level (0.1-1 μm) validation approach was used to compare the predicted collagen fiber/fibril mechanical behavior with extant MV small angle X-ray scattering data. Results demonstrated excellent agreement, indicating that the MSSCM fully captures the tissue-level function. Future utilization of the MSSCM in computational models of the MV will aid in producing highly accurate simulations in non-physiological loading states that can occur in repair situations, as well as guide the form of simplified models for real-time simulation tools.
深入理解二尖瓣（MV）疾病的病理生理重塑的基础是建立一个准确的组织水平本构模型。在本研究中，我们为MV瓣叶组织开发了一种新型的中尺度（即纤维水平，长度尺度为10 - 100μm）结构本构模型（MSSCM）。由于其四层结构，我们重点关注了每个组织层内不同的胶原和弹性纤维网络的贡献。使用二次谐波产生显微镜和传统组织学对每层所需的胶原和弹性纤维结构信息进行了量化。还使用了一个全面的力学数据集来指导模型公式的制定和参数估计。此外，对于组织水平结构本构建模方法来说新颖的是，我们允许胶原纤维募集函数随方向变化。结果表明，MSSCM预测的平均有效胶原纤维模量出人意料地一致，为162.72MPa，并在超生理负荷状态下表现出出色的预测能力。前后瓣叶之间也存在特定差异，例如前瓣叶中胶原和弹性纤维方向分布（ODF）更紧密，而后瓣叶中的心房肌层更厚且更硬。虽然观察到一定程度的角度变化，但紧密的瓣膜组织ODF也使得纤维力学响应中几乎没有任何物理上有意义的角度变化空间。最后，使用一种新型的原纤维水平（0.1 - 1μm）验证方法，将预测的胶原纤维/原纤维力学行为与现有的MV小角X射线散射数据进行比较。结果显示出极好的一致性，表明MSSCM完全捕捉到了组织水平的功能。MSSCM未来在MV计算模型中的应用将有助于在修复情况下可能出现的非生理负荷状态下进行高精度模拟，并为实时模拟工具的简化模型形式提供指导。
