Biomimetic matrices for pelvic floor repair

Pelvic organ prolapsed (POP) is a dysfunctional disease in female pelvic floor that affects a lot of women worldwide, and reduces their quality of life. Currently, trans-vaginal knitted polypropylene meshes are used as secondary treatment, for anatomical correction of the dysfunctional tissues. However, the meshes can create sever adverse complications in some patients, such as chronic pain and dypareunia, in longer-term. In the hope of finding an alternative surgical treatment, we developed nanofibrous matrices produces by electrospinning, based on different degradable and non-degradable materials. These electrospun matrices resemble the natural architecture of the extracellular matrix (ECM) and therefore considered as "biomimetic". In this thesis, we demonstrated through in-vitro models, that such synthetic mimic of the ECM, facilitates the adhesion of both healthy and diseased (from POP-patients) human vaginal fibroblasts to the biomaterial and therefore improves their interactional functions like proliferation and new collagen deposition. In addition, we showed that changing the micro-structural properties of the biomimetic matrices, such as fiber size, impacts not only the mechanical behaviour of the matrices but also the cellular responses. This finding can be used as a baseline for design of the new generation of biomimetic implants for pelvic floor. Further, we designed an in-vitro dynamic culture system, in which cell-seeded matrices were subjected to cyclic mechanical loading. Our finding revealed that a gentle straining of POP-cells on electrospun matrices, advances their regenerative potential at morphological and gene expression levels. Taken together, the findings of this thesis, provides a proof-of-concept for using electrospun matrices as an alternative implant for pelvic floor repair, given that in future studies the design parameters are proved efficient and safe.