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Description
Introduction:
With the aim of restoring both the structure and the function of the damaged ureter, the most common medical approaches involve the use of autologous tissue or cells transplants. However, there are many complications that hamper a total or even partial ureter regeneration. Therefore, ureteral regeneration is still a medical unresolved challenge. In this field, electrospun scaffolds are becoming to be considered as a valid alternative to transplants thanks to their biocompatibility, extracellular matrix (ECM) mimicry, slow biodegradability, suitable mechanical properties, and to their ability to sustain cell adhesion and proliferation. To discourage infections of the urinary tract (UTIs) and medical device-related infections (MDRIs), it is important to implement the scaffolds with antibiotic molecules. Rifampicin was found to be effective against the most represented pathogens of UTIs and MDRIs, respectively E. coli and S. aureus. In this work, antibacterial electrospun polycaprolactone-based tubular scaffolds enriched with rifampicin were produced, characterized and proposed as promising candidates for ureteral regeneration.
Methodology:
Electrospun polycaprolactone (PCL) and polycaprolactone-rifampicin (PCL/Rif) membranes were obtained and characterized. Given the hydrophobic nature of PCL, all membranes were treated with air-plasma cleaning process. Successively, the wettability was evaluated on both the groups of membranes. The membranes were aged in Simulated Body Fluid (SBF) at 37 °C and then analyzed by uniaxial tensile tests and SEM imaging in order to assess their stability. Rifampicin release kinetic was assessed by means of UV spectrophotometry. To investigate antibacterial efficacy of PCL/Rif membranes, E. coli and some bacteria strains belonging to the “ESKAPE” (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacter spp.) group were used. Moreover, the biocompatibility of membranes was tested evaluating urothelium cells (UCs) adhesion and proliferation. Material cytotoxicity was assessed evaluating Lactate Dehydrogenase (LDH) release from UCs.
Results:
The PCL membranes produced in this work present homogeneous nanofibers without surface defects. The addition of Rif results in a decrease of the average nanofiber diameter. PCL- membranes treated with plasma and PCL/Rif-loaded resulted to be very hydrophilic unlike untreated PCL membranes. The mechanical characterization, carried out with uniaxial tensile tests, showed a proper stability of the membranes aged in SBF, in terms of deformation at break, elastic modulus and maximum stress and a mechanical behavior suitable for ureter regeneration. The evaluation of the Rif release kinetics showed a burst release of rifampicin in the first 24 hours followed by a release decay. PCL-based membranes were able to sustain UCs adhesion and proliferation over time (confirmed by SEM investigation), but only the ones treated with Rif were able to inhibit bacterial proliferation. Moreover, the absence of cytotoxic effects of Rif was demonstrated by means of LDH assay.
Conclusions:
The satisfactory stability, mechanical, biological and antibacterial properties of the electrospun PCL membranes here produced and characterized set the basis for the development of a tubular scaffold which is promising in providing a valid alternative to transplants practice for the ureteral regeneration. Further in vivo analyses are needed to test and characterize these PCL based tubular scaffolds.
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