Urinary bladder in vitro regeneration: mechanical stimuli effects during tissue maturation


People involved: Monica Soncini, Gianfranco Beniamino Fiore, Filippo Consolo

Funding source: Italian Research Ministry Grant

Grant number: PRIN-2008-YZNAHR

Funding period: 2010 - 2012

Partners: Veterinary Faculty, Università degli Studi di Milano; Department of Mechanics, Politecnico di Torino, Department of Industrial and Mechanical Engineering, Università degli Studi di Catania; Department of Mechanics and Industrial technologies, Università degli Studi di Firenze.

The lack of autologous tissues fit for the replacement or for the reconstruction of the urinary bladder has led to the demand for alternative strategies of regeneration, both in vivo and in vitro, that make use of either naturally derived materials (collagen and alginate), or decellularized natural tissues (bladder or small intestine submucosa), or synthetic polymers (polyglycolic acid, PGA, polylactic acid, PLA, polylactide-polyglycolide copolymers, PLGA, Degrapol). Different approaches have been attempted: the direct in vivo implantation of biodegradable bioactive materials and the implantation of previously in vitro recellularized constructs. However, the results obtained show that cellular differentiation and extracellular matrix remodeling do not progress in the physiological manner. It is generally acknowledged that a cell culture in a proper biochemical environment, inside three-dimensional scaffolds, and with a mechanical stimulation similar to the one that the cells encounter in vivo could mimic the correct mechanotransduction mechanism that leads to a complete cellular differentiation.
The key role of physical stimuli in modulating cell function and in guiding in vitro tissue growth results in the development of functional systems models for in vitro recellularization. These systems expose the recellularized scaffold to possibly relevant mechanical stimuli. Moreover, compared to static culture, a dynamic system guarantees an enhanced scaffold perfusion and an automated medium and growth factors recirculation, besides allowing the online monitoring and control of significant culture parameters. The use of these systems for the in vitro regeneration of bladder tissue has two objectives: the former is to understand and analyze the effects that mechanical stimulation has on the growth and on the mechanical properties of the engineered tissue, the latter is to obtain such recellularized tissues from autologous cells, fit for implantation and with physiological-like mechanical properties.
Given this background, the specific project regards the engineering of the urinary bladder tissue, with the aim to assess the effect of mechanical stimulation on the in vitro maturation of the tissue. In order to actuate the strategies necessary for the good outcome of the project, which is inherently inter- and multi-disciplinary, the team consists of participants with technical and engineering know-how (Bioengineering Department of the Politecnico di Milano) and participants with specific knowledge in veterinary science and in preliminary cell cultures aimed at verifying the technologies and the strategies put in action in the project (Veterinary Clinical Sciences Department, Veterinary Faculty of the Università degli Studi di Milano).