Department of Mechanical Engineering, University of Connecticut, Storrs, CT, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.
J Mech Behav Biomed Mater. 2021 Jan;113:104127. doi: 10.1016/j.jmbbm.2020.104127. Epub 2020 Oct 10.
Mechanotransduction, the encoding of local mechanical stresses and strains at sensory endings into neural action potentials at the viscera, plays a critical role in evoking visceral pain, e.g., in the distal colon and rectum (colorectum). The wall of the colorectum is structurally heterogeneous, including two major composites: the inner consists of muscular and submucosal layers, and the outer consists of circular muscular, intermuscular, longitudinal muscular, and serosal layers. In fact the colorectum presents biomechanical heterogenity across both the longitudinal and through-thickness directions thus highlighting the differential roles of sensory nerve endings within different regions of the colorectum in visceral mechanotransduction. We determined constitutive models and model parameters for individual layers of the colorectum from three longitudinal locations (colonic, intermediate, and distal) using nonlinear optimization to fit our experimental results from biaxial extension tests on layer-separated colorectal tissues (mouse model, 7×7 mm, Siri et al., Am. J. Physiol. Gastrointest. Liver Physiol. 316, G473-G481 and 317, G349-G358), and quantified the thicknesses of the layers. In this study we also quantified the residual stretches stemming from separating colorectal specimens into inner and outer composites and we completed new pressure-diameter mechanical testing to provide an additional validation case. We implemented the constitutive equations and created two-layered, 3-D finite element models using FEBio (University of Utah), and incorporated the residual stretches. We validated the modeling framework by comparing FE-predicted results for both biaxial extension testing of bulk specimens of colorectum and pressure-diameter testing of bulk segments against corresponding experimental results independent of those used in our model fitting. We present the first theoretical framework to simulate the biomechanics of distal colorectum, including both longitudinal and through-thickness heterogeneity, based on constitutive modeling of biaxial extension tests of colon tissues from mice. Our constitutive models and modeling framework facilitate analyses of both fundamental questions (e.g., the impact of organ/tissue biomechanics on mechanotransduction of the sensory nerve endings, structure-function relationships, and growth and remodeling in health and disease) and specific applications (e.g., device design, minimally invasive surgery, and biomedical research).
机械转导，即将感觉末梢处的局部机械应力和应变编码为内脏中的神经动作电位，在引起内脏疼痛方面起着关键作用，例如在远端结肠和直肠（结肠直肠）中。结肠直肠壁结构不均匀，包括两个主要复合材料：内层由肌肉和黏膜下层组成，外层由环形肌肉、肌间、纵形肌肉和浆膜层组成。事实上，结肠直肠在纵向和贯穿厚度方向上都呈现出生物力学异质性，这突出了不同区域的感觉神经末梢在内脏机械转导中的差异作用。我们使用非线性优化方法从三个纵向位置（结肠、中间和远端）确定了结肠直肠各个层的本构模型和模型参数，以拟合我们在层分离的结肠直肠组织（小鼠模型，7×7 毫米，Siri 等人，Am. J. Physiol. Gastrointest. Liver Physiol. 316，G473-G481 和 317，G349-G358）的双向拉伸试验的实验结果，并量化了层的厚度。在这项研究中，我们还量化了将结肠直肠标本分离成内外复合材料所产生的残余拉伸，并完成了新的压力-直径机械测试，以提供额外的验证案例。我们实施了本构方程，并使用 FEBio（犹他大学）创建了两层、三维有限元模型，并纳入了残余拉伸。我们通过比较对大块结肠直肠组织进行双向拉伸测试和对大块段进行压力-直径测试的 FE 预测结果与独立于我们模型拟合的实验结果，验证了建模框架。我们提出了第一个理论框架，基于对小鼠结肠组织的双向拉伸测试的本构建模，模拟远端结肠直肠的生物力学，包括纵向和贯穿厚度异质性。我们的本构模型和建模框架促进了对基本问题（例如，器官/组织生物力学对感觉神经末梢机械转导的影响、结构-功能关系以及健康和疾病中的生长和重塑）和具体应用（例如，器械设计、微创手术和生物医学研究）的分析。
