Role of elastin in vaginal wall biaxial mechanical response with experimental and mathematical approaches
Progress towards understanding the underlying mechanisms of pelvic organ prolapse (POP) is limited, in part, due to a lack of information on the biomechanical properties and microstructural composition of the vaginal wall. Compromised vaginal wall integrity is thought to contribute to pelvic floor disorders. In particular, disruption of the elastin metabolism within the vaginal wall extracellular matrix has been highly implicated in POP pathogenesis; however, the role of elastin within the vaginal wall is not fully understood. In addition to the information produced from uniaxial testing, biaxial extension-inflation tests performed over a range of physiological values could provide additional insights into vaginal wall mechanical behavior (i.e. axial coupling and anisotropy) while preserving in vivo tissue geometry. Thus, the objective of this study is to identify the role of elastin in vaginal wall mechanics using physiologically relevant experimental and mathematical approaches. Our specific aims are thus: 1. Develop biaxial mechanical testing methods for assessing the mechanical properties of the murine vaginal wall in a physiological manner. 2. Establish a microstructurally-motivated constitutive model capable of describing the biaxial extension-inflation response of the nonpregnant murine vaginal wall. 3. Quantify the role of elastin in murine vaginal mechanical properties through enzymatic digestion of elastin with elastase.Vaginal tissue from female C57BL/6 mice underwent pressure-diameter and force-length preconditioning and testing within a pressure myograph device before and after elastase digestion. In order to mathematically interpret biaxial data, vaginal tissue was modeled using a 2D membrane approach. Several constitutive models were evaluated on their ability to describe vaginal wall mechanical behavior. Elastase digestion induced marked changes in biaxial mechanical properties, suggesting that elastin may play an important role in vaginal wall mechanical function. Constitutive model evaluation resulted in the selection of a diagonal two-fiber family strain energy function and suggests that collagen fibers within the vaginal wall extracellular matrix (ECM) may be primarily oriented diagonally with a slight preference towards the circumferential direction. Further, our results suggest that elastin-collagen interactions may be important for vaginal wall homeostasis. The present findings may help to understand the underlying mechanisms of POP and aid in the development of growth and remodeling models for improved assessment and prediction of changes in structure-function relationships with prolapse development.