Biomechanical impact of menopausal transition on pelvic soft tissues: characterizing and modelling tissue fragility
Description
Menopause is a major physiological transition characterized by a sharp decline in hormone levels (estrogens, progesterone) that profoundly affects the structure and mechanics of soft tissues [1,2]. These changes are associated with common pathologies: genital prolapse [3], urinary incontinence, joint pain, skin elasticity loss, and muscle weakening. Yet, the direct link between hormonal changes and the biomechanics of soft tissues remains poorly explored.
This project aims to fill this gap by investigating the biomechanical consequences of menopause on five pelvic-related soft tissues (skin, fascia, muscle, perineal connective tissue, vaginal mucosa), building upon the PELVITRACK Pathfinder project (Grant 101186212). Ex vivo porcine tissues degraded enzymatically (collagenase, elastase…) will serve as reproducible proxy of estrogen-deficiency remodeling [4,5], capturing the key biomechanical effects of tissue degradation [6], while not replicating the full hormonal regulation of menopause.
The key objective of this work is to establish objective biomechanical markers of tissue stiffening and fragility, as well as microstructural alterations caused by these enzymatic degradation.Mechanical testing will include uniaxial and biaxial tensile tests, and fracture-oriented CT tests specifically designed for soft biological tissues. Mechanical responses will be characterized in terms of hyperelasticity, viscoelasticity, Mullins effect [7] and damage. Tissue fragility and rupture mechanisms will be analyzed using a phase- field modeling approach [8]. IMT Mines Alès and Mines Saint-Étienne offer strong complementarity: Alès provides expertise in advanced experimental mechanics and constitutive modeling, while Saint-Étienne brings expertise in experimental biomechanics, rupture, and phase-field modeling. Histology will identify structural markers (collagen, elastin) and muscle proteins (actin, myosin, desmin), complementing mechanical data. Results will be integrated into a predictive framework of fragility and stiffening, as a first step toward a digital twin of the menopausal transition. Innovation lies in combining biomechanics, advanced modeling, histology, and clinical perspectives. Outcomes include: (i) a innovative CT device for fracture in pelvic tissues, (ii) biomarkers of menopausal fragility, and (iii) an original integration of enzymatic ex vivo models with advanced constitutive laws and phase-field damage. These advances will set new methodological standards for soft tissue biomechanics. Regular consultation with gynecologists will align findings with clinical needs, reinforcing translational impact. In the longer term, this thesis open perspective toward Horizon Europe/ ERC projects, aiming at a comprehensive vision of menopause encompassing bone (osteoporosis), muscle (sarcopenia), skin and fascia (elasticity), cardiovascular system (stiffening, hypertension), neurovegetative functions (hot flashes, sleep), and even andropause in men. Potential impacts toward the medical device industry will be considered, particularly for the development of diagnostic or preventive tools if opportunities arise.
Bibliography
Bibliography
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