Pelvic floor dysfunctions (PFDs) are a group of disorders affecting one-third of women worldwide and 50% of women above 55, with pelvic organ prolapse (POP) being the most common. Nowadays, different approaches are used to treat POP, including a surgical approach that consists in the placement of a polymeric mesh. Unfortunately, the employment of meshes has been often associated with the development of significant side effects (e.g. fibrosis, infections, stress shielding). Moreover, in accordance to the United States Food and Drug Administration (FDA) updated guidelines, current marketed products lack of customisability and are unable to comply with the anatomy of the pelvic floor. Therefore, new material and manufacturing-based strategies have to be implemented in order to reduce the risks associated with the use of meshes and to guarantee their integration with the surrounding tissues. In this research work biodegradable, piezoelectric and antibacterial meshes made of polycaprolactone (PCL), polyvinylidene fluoride (PVDF) and levofloxacin (LFX), have been processed via melt-extrusion 3D printing (3DP) aiming to produce a drug-eluting implant with antibacterial activity and with the potential to actively trigger cells thus guiding tissue regeneration.
PCL, PVDF (5%, 10%, 16% w/w) and LFX (0.5% w/w) powders were dry mixed and then used to manufacture honeycomb-shaped meshes. All the raw materials were characterised according to their thermal behaviour, amount of beta phase and their physicochemical properties. The morphology of the produced meshes was analysed via scanning electron mycroscopy (SEM), whereas the mechanical behaviour and meshes storage stability were assessed via stability studies up to 4 months. In vitro tests were also performed (drug release, degradation behaviour, antibacterial potential, cytotoxicity) to assess meshes performances.
Among the tested concentrations the one containing 5% w/w of PVDF proved to be the most appropriate in terms of printability and mechanical behaviour. Thermal analysis showed that no degradation occurred during manufacturing. The amount of beta phase within the different samples did not change significantly after printing and it was around 60% for all samples tested. Meshes were characterised by large pores (1.20 mm), suitable to allow cells colonisation. The evaluated mechanical properties were compared with the native human ones, and found to be close to the physiological range (EPCL/5PVDF/0.5LFX=12.74 ± 0.26). Meshes were capable to release LFX for at least 72 hours, with 60% of the total drug released in three days from PCL/5PVDF/0.5LFX samples.
The results obtained within this study are promising, as they show how the produced meshes have the potential to satisfy the morphological and mechanical requirements to successfully manage POP, but also, considering the evaluated release profile, and thanks to their high pre-poling amount of beta phase, the potential to recruit fibroblasts by exerting an antibacterial action and piezoelectric effect.