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Farhat Lab
Farhat Lab

Bioreactor and biomechanical stimulation

Evidence in the field now supports the idea that in-vitro-propagated autologous cells seeded on scaffolds prior to implantation may be necessary for reconstitution of bladder defects. Studies have shown that in vitro cell and tissue growth are enhanced in response to mechanical stimulation similar to normal physiologic conditions when compared to cells grown under the static conditions. Furthermore, mechanical stimulation influences cellular alignment and induces favourable proliferative changes. This stimulation also induces cells to lay down extracellular matrix components that are suitably organised physically and mechanically when the cell/scaffold construct is implanted.

In our laboratory, using a biodegradable natural scaffold we have developed and modified a tissue engineered urinary construct that provides a suitable three-dimensional matrix for in vitro cell attachment. With evidence that mechanical stimulation positively influences, cell proliferation differentiation and protein synthesis, we sought to mimic in vivo urinary bladder dynamics by devising a tissue bioreactor that imitates the bladder mechanical environment observed in fetal life. Bioreactors have been investigated and used extensively in the cardiovascular literature; these bioreactors are devised to generate mechanical stimuli (pressure 90-120mmHg) that are not useful for low pressure dynamic organs such as urinary bladders or gastrointestinal tracts (5-10 cm H2O). On the other hand, devices rather than bioreactors for urinary bladder research have been describe. In these devices, mechanical stimuli were applied simultaneously using a pneumatic or vacuum pulsating method that provided only a limited range of mechanical environments that were not similar to the normal developing urinary bladder.

Our devised bioreactor would simulate normal urinary bladder function while enabling close monitoring of biomechanical and biochemical controls. A series of studies were performed to validate the performance of the bioreactor. With an earlier prototype consisting of two separate plexiglass chambers, a combination of pressure sensors, mechanical pressure controllers and computer software were devised to produce the proper pressure characteristics under a closed loop configuration.

Our goal is to develop a urinary bladder bioreactor with efficient process monitoring that reliably and reproducibly recapitulates in vivo bladder function. Important bioreactor design criteria include the ability to regulate mechanical and nutrient environments to promote cell proliferation, differentiation, and favourable matrix deposition. The critical research question is whether mechanical stimuli will effectively and efficiently enhance bladder tissue reconstitution suitable for direct bladder replacement and clinical application.

Our research goal is to reconstitute in vitro the cellular and acellular components of normal urinary bladder tissue with all the appropriate cellular physical and mechanical characteristics, i.e. impermeable and compliant. Studies in our laboratory are underway to assess the impact of low pressure cyclic mechanical stimulation on the urinary bladder cell seeded constructs; histological and functional outcomes.