Rifampicin-loaded electrospun polycaprolactone membranes: Characterization of stability, antibacterial effects and urotheliocytes proliferation

Pathological conditions such as infections, cancer, inflammation, or iatrogenic lesions, can hinder the cor-rect functionality of the ureter and its structural integrity. Several strategies for the regeneration of the ureter and the restoration of its functionality are available but the best strategy has not been reached yet. Among the proposed strategies, a promising one is the development of tubular scaffolds, in particular exploiting electrospinning technique. In this work, antibacterial electrospun polycaprolactone/rifampicin (PCL/Rif) membranes were prepared and characterized. The membranes are characterized by randomly oriented nanofibers with a homogeneous diameter, as determined by scanning electron microscopy. The mechanical characterization, performed with uniaxial tensile tests, showed a suitable stability over time and a proper deformability. The rifampicin release, investigated by UV spectrophotometry, showed a burst release in the first part of the experiment and a sustained release over time. The membranes are biocompatible and able to support the adhesion and proliferation of urotheliocytes. Moreover, PCL/Rif membranes showed an antibacterial activity against Escherichia coli and other bacterial strains belonging to the "ESKAPE" group. Considering the possibility to use the electrospinning for the production of tubu-lar scaffolds, the described membranes represent a promising starting point for the preparation of uret-eral scaffolds with antibacterial properties.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Antibacterial rifampicin-loaded electrospun polycaprolactone membranes for ureteral regeneration

Author of the study: Nowadays partial or complete ureteral loss following resection or injuries of various etiology is managed with different surgical techniques involving local tissue flaps or autologous tissues interposition. In the last years ureteral tissue engineering using membranes, tubular scaffolds or decellularized matrices has shown promising results for ureteral substitution. The aim of this study is to evaluate the use of antibacterial electrospun polycaprolactone/ rifampicin (PCL/RIF) membranes for the production of ureteral scaffolds with antibacterial properties. Materials and methods: Electrospinning processwas used to produce the membranes that were subsequently impregnated with rifampicin. Membranes stability was evaluated by immersion in Simulated Body Fluid (SBF) at 37 °C. Mechanical properties were evaluated by uniaxial tensile tests, Young’s modulus was calculated for each sample. UV spectrophotometry was used to evaluate in vitro release of rifampicin. The ability of PCL/Rif membranes to sustain cell adhesion and proliferation was evaluated by seeding human urothelial bladder carcinoma cells on the membranes. In order to investigate the antibacterial effect of PCL/Rif membranes, in vitro antibacterial tests were performed using bacterial strains belonging to the “ESKAPE” group. Results: PCL/Rif membranes are characterized by a random distribution of fibers with an average diameter of 0.52 μm.Water contact angle for PCL and PCL/Rif membranes is around 125° and decreases to 0° after air-plasma treatment. When culture medium is used as testing fluid PCL and PCL/Rif contact angles are 116° and 12° respectively. Membranes are deformable up to 300% of their initial dimension and possess an elastic Young modulus of about 20 kPa; after 3 weeks membranes gain the property to sustain a 100% deformation before rupture. The 72% of rifampicin load is released by the membranes in the first 24 hours. Proliferation assay showed a seven-fold increase of cell number adhered on the membranes after 7 days of culture. At the same time in presence of PCL/Rif membranes, rates of bacterial proliferation inhibition ranged from 75 to 94% compared to controls. Conclusions: PCL/Rif membranes represent a promising starting point in the production of ureteral scaffolds with antibacterial properties for ureteral substitution

A new role for the P2Y-like GPR17 receptor in the modulation of multipotency of oligodendrocyte precursor cells in vitro

Oligodendrocyte precursor cells (OPCs, also called NG2 cells) are scattered throughout brain parenchyma, where they function as a reservoir to replace lost or damaged oligodendrocytes, the myelin-forming cells. The hypothesis that, under some circumstances, OPCs can actually behave as multipotent cells, thus generating astrocytes and neurons as well, has arisen from some in vitro and in vivo evidence, but the molecular pathways controlling this alternative fate of OPCs are not fully understood. Their identification would open new opportunities for neuronal replace strategies, by fostering the intrinsic ability of the brain to regenerate. Here, we show that the anti-epileptic epigenetic modulator valproic acid (VPA) can promote the generation of new neurons from NG2+ OPCs under neurogenic protocols in vitro, through their initial de-differentiation to a stem cell-like phenotype that then evolves to \u201chybrid\u201d cell population, showing OPC morphology but expressing the neuronal marker \u3b2III-tubulin and the GPR17 receptor, a key determinant in driving OPC transition towards myelinating oligodendrocytes. Under these conditions, the pharmacological blockade of the P2Y-like receptor GPR17 by cangrelor, a drug recently approved for human use, partially mimics the effects mediated by VPA thus accelerating cells\u2019 neurogenic conversion. These data show a co-localization between neuronal markers and GPR17 in vitro, and suggest that, besides its involvement in oligodendrogenesis, GPR17 can drive the fate of neural precursor cells by instructing precursors towards the neuronal lineage. Being a membrane receptor, GPR17 represents an ideal \u201cdruggable\u201d target to be exploited for innovative regenerative approaches to acute and chronic brain diseases

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services