Magee-Womens Research Institute & Foundation

Damage to the muscles and tissues that provide support to the pelvic organs at the time of vaginal birth can lead to debilitating conditions across the female lifespan. Unfortunately, scientifically based therapies to treat these disorders are sparse. We aim to improve the lives of women by improving the efficacy of current treatments and developing novel therapies specifically targeted at repairing underlying injury.
Pamela Moalli, MD, PhD

Research in Brief

Translational Research Laboratories in Urogynecology (TRLU): Co-directed by Pamela Moalli, MD PhD and Steve Abramowitch, PhD, the overarching goal of this collaboration is to contribute insights into the pathogenesis, diagnosis, and treatment of pelvic organ prolapse and urinary incontinence – two common pelvic floor disorders. Their main areas of research focus are 1) comprehensive analysis of commonly used biomaterials in urogynecologic procedures 2) defining mechanisms of failure after reconstructive pelvic surgeries, 3) designing novel devices for surgical repair 4) defining mechanisms of maternal birth injury, 5) and vaginal biofabrication for women experiencing massive tissue loss. The group has expertise in computational modeling, cellular and molecular biology including both traditional and high throughput platforms, soft tissue mechanics, mechanobiology, tissue regeneration and immunomodulation.

TRLU’s current portfolio of investigations include:

Synthetic materials for urogynecologic applications: The group is a world leader in studies defining the impact of commonly used urogynecologic meshes on the vagina in animal models (primate) and women, modifying the host response to improve long term outcomes, and developing materials that are designed specifically to match the properties of the vagina. In ex vivo mechanical tests in conjunction with computational analyses, they have clearly demonstrated that prolapse meshes often have markedly unstable geometries with a dramatic loss of porosity with small applications of tension and that stresses imposed on the vagina by the mesh have significant regional variability. These effects are largely driven by modifiable factors including the pore geometry of the mesh, the degree of tension, and how the mesh is anchored. Indeed, the group’s experimental and computational model predictions of the impact of these mechanical effects are confirmed in mesh explants removed from women with mesh complications which demonstrate buckles, folds, and pore collapse. Using ex vivo mechanical tests in conjunction with animal models and computational analyses, the group has demonstrated that most mesh used for incontinence and prolapse surgery have unstable geometries with a loss of porosity under modest tension. They have demonstrated that this is a mechanism for complications (exposures and visceral erosions). The group is currently developing a new generation of meshes based on elastomeric polymers and stable geometries as an alternative to current polypropylene meshes which plastically deform when loaded. In addition, they are working towards personalized meshes based on 3D modeling of an individual patient’s vagina and specific support defects with the idea that it is unlikely that a single mesh type and geometry is an appropriate match for all women with prolapse. The group is building more comprehensive computational models to provide insight into mechanisms of maternal injury at the time of vaginal birth. Finally, they are fabricating synthetic mechanical niches for engraftment of vaginal stem cells for use in vaginal biofabrication.