NSF Award
2038515
Non-Technical Summary: <br/><br/>Pelvic organ prolapse (POP) occurs when decreased pelvic muscle strength results in pelvic organs such as the bladder or ovary, distending into the vagina, causing significant pain and discomfort and leading to a lower quality of life. Till recently, POP was addressed surgically by the use of synthetic polypropylene meshes to mechanically support and hold up the pelvic organs. However, the biological and mechanical properties of polypropylene are very different from those of pelvic organs. Hence, this difference created inflammation and damage of the pelvic tissues, which in turn caused oxidation of the meshes leading to their eventual breakdown. This cycle of events leads to eventual organ damage and chronic pain. Due to such complications in a large number of women, the FDA has withdrawn permission for the use of such meshes for POP and currently there are no surgical meshes available for POP. Hence, there is a critical need for examination of alternative materials as replacements for polypropylene and to understand the features of the mesh materials that lead to deleterious reactions. This study will design and 3D print a set of polyester and polyurethane meshes as alternatives for polypropylene meshes. Subsequently, these meshes will be tested to determine how cells react to the mesh chemistry and geometrical features. In addition, the mechanical strength and elasticity of the meshes will be examined before and after treating them in conditions that cause oxidative damage to the meshes. Such systematic studies will provide a deeper understanding of the chemical and physical features of mesh materials that affect biological reactions. The results from this study will also be useful for the FDA in their evaluations and regulation of POP meshes. <br/><br/>Technical Summary: <br/><br/>Advancing age or multiple childbirths increase the probability of pelvic organ prolapse (POP), which is the herniation of the pelvic organs into the vagina due to the weakening of the pelvic floor muscles and connective tissues. Each year, about 240,000 prolapse procedures are performed in the United States and 11% of women will undergo corrective surgery in their lifetime to address prolapse. Till recently, propylene meshes were used to support the distending pelvic organs by attachment to the sacrospinous ligament and/or the arcus tendineus fascia pelvis. However, polypropylene meshes are both biologically and mechanically incompatible with the soft and elastic tissues of the pelvic cavity and have been shown to promote inflammatory reactions leading to eventual mesh failure. Due to the poor biomechanical compliance and resultant complications such as chronic pain, organ perforation and recurrent infections, the FDA has banned the use of existing surgical meshes for transvaginal POP repair. Hence, there is an unmet need for POP meshes that will provide mechanical support without causing inflammatory reactions or pelvic organ damage. The project will compare a set of biomaterials and mesh architectures to identify critical parameters that influence mechanical stability and cellular responses with the aim of providing a deeper understanding for the design of materials for POP repair. The data generated through this study will be useful for the FDA for the evaluation and regulation of synthetic materials as replacements for polypropylene. A set of pendant functionalized polyesters and polyurethanes will be used to fabricate 3D printed meshes with auxetic geometries and these will be used to evaluate proliferation and cytocompatibility of fibroblasts on the meshes. Furthermore, macrophage behavior and ROS production in presence of the meshes will be evaluated. It is hypothesized that oxidation of the meshes, either due to external or biological oxidants, result in catastrophic loss of mechanical properties of the meshes. Hence, the mechanical properties of the meshes, both before and after exposure of the meshes to external oxidants will be evaluated. In addition, the mesh degradation products will be characterized through various methods including HPLC, NMR, UV-Vis, ATR-FTIR and SEM.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
