Resorbable nanostructured biomaterials for ureteral regeneration: development, biological characterisation and computational modelling
Progetto The use of an engineered scaffold is the most encouraging approach for
ureteral tissue regeneration. An ideal resorbable scaffold is biocompatible and biodegradable and exhibits cardinal structural features as porosity, flexibility and retention of the luminal
patency. Moreover, it should be ìmpermeable to urine while providing a suitable substrate for cell colonization and tissue
remodelling. This project has three main objectives: (i) to develop a resorbable scaffold for ureteral tissue regeneration; (ii) to
biologically characterize it in vitro and (iii) to implement a mathematical model to describe and predict the scaffold structural
response to any condition which can trigger its collapse in a virtual in vivo situation. Moreover, scaffold’s biodegradability and the
simultaneous tissue regeneration processes will be virtually simulated based on the biological and structural data obtained from
laboratory experiments performed on the structures developed in this study. The project involves the efforts of two research units,
each with specific expertise and roles, which will interact during all the phases of the project. Unitl will exploit the electrospinning
technique that allows for the fabrication of nanostructured fibrous tubular scaffolds. During the project, the structural features of the
biomaterial will be finely tuned based on the feedback given by the biological tests (Unit2-Bio) and mathematical models
(Unit2-Comp). Unit 2-Bio will investigate the behavior of human primary urothelial and bladder smooth muscle cells when seeded on
the two surfaces (inner and outer) on the scaffold. Cell proliferation,
cytotOxlcity, occurrence of inflammation, oxidative stress and apoptosis will be evaluated, as well as the expression of molecules of adhesion and related signaling. The scaffold influence on the
immune response will be explored on a co-culture of human monocytes and
primary bladder fibroblasts, in order to bring out
paracrine signal exchange. Unit 2-Comp will develop a virtual numerìcal
laboratory aimed to solve specific differential equations of
computational fluid dynamics. Mathematical models wlll be developed to evaluate the scaffold degradation, the cell-biomaterial
interaction and the infiltration-filtration processes of the urinary fluid through its internal walls. For the latter phenomenology, the suitability of the advanced mathematical technique of fractional derivatives, which have found useful applications in anomalous
diffusion processes in non-homogeneous materials, will also be explored. If granted, the results of this project will mark a significantprogress towards the tissue regeneration of the ureter. The combination of structural and biological in vitro results obtained from the
constructs here investigated could pave the road for a clinical phase.
Moreover, the production of the scaffolds could be easily
translated from the laboratory to the marketplace allowing for progress in
both scientific and industrial fields.