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Biology subjects

Tirelli, N.

Publications and source records attributed to Tirelli, N..

3 recordsLinked to original sources

On the biodegradation of micropatterned polymeric film

AO_SCPLOWBSTRACTC_SCPLOWPolymeric implants for local drug delivery offer significant advantages for treating various medical conditions by enabling the temporal and spatial control of drug release, improving efficacy, and reducing systemic side effects. In this context, {micro}MESH, a 20 m thin, dual-compartmentalized film comprising a poly(lactic-co-glycolic acid) (PLGA) micronetwork intercalated with a polyvinyl alcohol (PVA) microlayer, represents an interesting opportunity as its geometry can be systematically and accurately micropatterned during the fabrication process, enabling the systematic analysis of the effect of geometry on biodegradation rates mechanisms. In this study, four different {micro}MESH films were realized with different surface area-to-volume ratios (Sa/V), ranging from 0.67 to 1.7 {micro}m-1. After characterizing the {micro}MESH geometry via fluorescent and scanning electron microscopy, biodegradations studies were performed up to 60 days in different media to assess the mass loss of PLGA, the reduction in PLGA molecular weight, and the formation of macroscopic defects - pores, holes and crack - within the PLGA micronetwork. By comparing the four {micro}MESH films among themselves and to a flat, continuous PLGA slab (FLAT), it was confirmed the importance of the surface-to-volume ratio and demonstrated that {micro}MESH with higher Sa/V ratios exhibited slower degradation rates compared to FLAT. Scanning electron microscopy images of the PLGA micronetworks revealed morphological changes indicative of bulk erosion, including surface roughening and pore formation, in FLAT and {micro}MESH configurations with low Sa/V ratios. These findings confirm that film micropatterning significantly influences degradation kinetics.

bioengineering↗

Polysulfide Nanoparticles Ameliorate Ischaemia Reperfusion Injury in Renal Transplantation and Improve Kidney Function Post-Transplantation

Ischemia-reperfusion injury (IRI) is a significant complication in kidney transplantation, often affecting the viability and function of organs. Normothermic machine perfusion (NMP) is a technique used to improve the condition of organs prior to transplantation. In this study, we show that incorporating antioxidant poly(propylene sulfide) nanoparticles (PPS-NPs) during cold-storage and NMP significantly enhances its efficacy in reducing IRI upon porcine kidney transplantation. We found that by scavenging reactive oxygen species, PPS-NPs reduced oxidative stress and inflammation that occurs during ischemia-reperfusion with oxidized DNA reduced 5.3x and both TNF- and complement activation approximately halved. Our studies show that this approach led to significantly improved hemodynamics, better renal function, and tissue health compared to NMP alone. The results suggest that incorporating PPS-NPs into transplantation protocols may expand the pool of kidneys suitable for transplantation and enhance overall transplantation success rates. The broader impact of this work could extend to other organ transplants, suggesting a wider application for nanoantioxidant technologies in organ preservation.

synthetic biology↗

RAD51 nuclear recruitment and inhibition towards innovative strategies against pancreatic cancer

RAD51, a key player in the homologous recombination (HR) mechanism, is a critical protein to preserve genomic stability. BRCA2, upon DNA damage, promotes RAD51 fibrils disassembly and its nuclear recruitment. Here, we use BRC4, a peptide derived from the fourth BRC repeat of BRCA2; BRC4 induces RAD51 defibrillation through a domino effect, eroding fibrils from their termini, and yielding monomeric RAD51. The congruence among several techniques (static and dynamic light scattering, negative staining transmission electron microscopy (TEM), and microscale thermophoresis) allows an accurate estimation of the kinetic and thermodynamic parameters of this process. BRC4 lacks, however, a nuclear localization sequence; therefore, it cannot transport RAD51 into the nucleus, thus behaving as a RAD51 inhibitor. Cellular assays (BxPC-3, pancreatic cancer cells) indeed show that BRC4 efficiently inhibits HR and enhances the cytotoxic effect of cisplatin, a DNA-damaging drug. The present study sheds further light on the complexity of the HR pathway, paving the way for designing peptide and small organic molecule inhibitors of RAD51 as innovative anticancer and chemo/radiosensitizer compounds.

biophysics↗