A Novel Multiscale Multiphasic Structure-Based Modeling Framework for the Intervertebral Disc

The overall goal of the dissertation research is to provide insights into the fundamental structure-composition-function relationship in lumbar intervertebral discs. The research develops and validates a novel multiscale multiphasic structure-based framework for modeling the intervertebral disc and soft fiber-reinforced biological tissues with accuracy, robustness, and translatability, which helps elucidate important stress-bearing mechanisms in both healthy and degenerated disc tissues. The proposed modeling framework and the subsequent model outcomes could have broad scientific and clinical implications related to the development of in vitro testing protocols with improved effectiveness, robustness, and clinical relevance, the design of novel tissue-engineered structures, and the evaluation of subfailure and failure behaviors in healthy and pathological tissues. Ultimately, the hope is that the modeling framework presented and validated in the current work can serve as a foundation for developing and validating future intervertebral disc and fiber-reinforced biological tissue models with patient-specific geometries, morphologies, and pathologies, and the resulting models can be used to improve clinical outcomes of low back pain treatments and, in turn, contribute to the broad effort of addressing this global health concern./nThis dissertation comprises a series of separate, but related finite element modeling studies that focus on the development, validation, and application of the proposed models. The goals of these studies are to obtain an accurate, robust, and translatable finite element modeling framework to investigate multiscale and multiphasic disc mechanics, including, but are not limited to, joint stiffness and the stress-bearing contribution of the interstitial fluid at the joint scale, annulus fibrosus (AF) uniaxial tensile mechanics at the tissue scale, and AF stress transmission mechanisms and fiber-matrix interactions at the subtissue scale, under various physiologically relevant boundary and loading conditions in both healthy and degenerated tissues./nThe primary results highlighted the accuracy, robustness, and translatability of the modeling framework proposed in the dissertation. Model predictions closely matched experimental measurements across the joint, tissue, and subtissue scales under various boundary and loading conditions with different specimen geometries. Joint- and tissue-scale model outcomes emphasized the significant stress-bearing role of the disc interstitial fluid content (i.e., the tissue water content accounted for up to ~60% of the joint’s stress-bearing capability in healthy discs), highlighting the necessity of multiphasic modeling. Tissue- and subtissue-scale model outcomes provided comprehensive explanations for the hard-to-interpret geometry dependence widely observed in AF tensile mechanics research and directly measured AF fiber stretch that were impossible to characterize during in situ and in vitro testing, highlighting the benefits of directly describing subtissue-level structures using the multiscale structure-based modeling approach./nModel outcomes also highlighted the importance of designing study-specific testing protocols based on individual research objectives. Particularly, physiologically representative specimen geometry, boundary condition, and loading condition should be applied if the measurements are intended to be interpreted in the context of clinical relevance, and vice versa. For example, in this dissertation, model outcomes across the joint, tissue, and subtissue scales helped identify the non-physiologically representative instantaneous center of rotation as a main issue for current herniation testing protocols, highlighting that the finite element models proposed in the current research could serve as a powerful yet effective complementary tool when designing testing protocols for resource- and time-intensive experiments./nIn conclusion, a novel multiscale multiphasic structure-based framework is developed and validated for modeling the intervertebral disc; the resulting finite element models are proven accurate, robust, and translatable. The proposed modeling framework provides an effective tool for directly investigating the multiscale disc mechanics, especially at the subtissue scale, with degeneration, disease, and injury. The modeling framework with the subsequent model outcomes has the potential to help lay the foundation for future experimental-computational combined research that aims to comprehend disc and soft tissue failure mechanisms, providing a powerful tool that complements clinical diagnoses and treatments for low back pain.

Advisor: O'Connell, Grace D