TRANSMEX

"The Balance between Transport and Mechanical Issues in 3D Regenerative Tissues, Using the Perfusion Bioreactor"

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 Obiettivo del progetto (Objective)

'Difficulties encountered in tissue engineering invited the use of perfusion bioreactors to deliver essential nutrients to cells within tissue-engineered constructs. Despite the increased nutrient transport achieved, solute perfusion caused harmful mechanical stresses to the cells. Interestingly, some bioreactors are employed to mechanically stimulate cells, improving their biological functions. However, stresses associated with perfusion bioreactors are counterproductive. Currently, to address this issue, perfusion rate is lowered to minimise mechanical implications to the cells. Consequently, nutrient delivery is sacrificed. Therefore, this project aims to balance the nutritional advantage offered by perfusion, and its associate cell-death. By doing so, essential nutrients may be perfused to all regions of tissue-engineered constructs, at flow rates whose mechanical implications are harmless, or even encouraging to cells. To alleviate the costly and iterative experiments necessary to achieve these aims, the use of computational modelling will be central to the project, and incidentally, forms the training objective of the proposal. However, key findings will be corroborated with laboratory experiments. Combining techniques associated with cell biology, material science, and mechanical engineering. The specific objectives of the proposed study are to: Model the fluid flow-induced deformation of cells within tissue-engineered constructs. Using fluorescent staining, corroborate relationship between fluid flow and cellular deformation. Design a system to mechanically deform cells without fluid flow. Investigate the influence of cellular deformation, with and without fluid flow to their viability and biological activities. Extrapolate the individual contributions of fluid flow and mechanical deformation. Determine theoretically, and experimentally, useful ranges of fluid flow and mechanical deformation, conducive to developing functional neo-tissues in vitro.'

Introduzione (Teaser)

The problems encountered in delivering essential nutrients to engineered tissues resulted in the introduction of perfusion bioreactors to work with cells cultured in 3D scaffolds. However, pressure generated by fluid flow during molecule transportation often harms the cells, sometimes even rendering them unusable.

Descrizione progetto (Article)

Although perfusion bioreactors have been successfully used to increase nutrient transport, it can often be a counterproductive process if it exerts harmful mechanical stresses on cultured cells. Lowering perfusion rates to minimise such negative outcomes can result in inadequate nutrient delivery once more.

'The balance between transport and mechanical issues in 3d regenerative tissues, using the perfusion bioreactor' (Transmex) is a project that aimed to find the balance between nutritional advantages offered by perfusion and associated cell-death. Specifically, the EU-funded project set out to model the fluid flow-induced deformation of cells in tissue-engineered constructs.

In activities directed at uncovering the advantages and limitations of media perfusion for neo-tissue development, researchers demonstrated an operational range of beneficial perfusion as well as the parameters defining this range. Results clearly showed the need to identify a perfusion system's operational capacity and the cell-scaffold model. In this way, a culture strategy can be maximised for efficient nutrient supply without applying detrimental pressure to either the cells or their seeding scaffold.

Since bioreactor pressure build-up during direct perfusion cannot be avoided, perfusion times logically dictate if there will be damage to the tissue and if the culture will be compromised. By acknowledging that pressures and timing differ from system to system, Transmex project partners proposed that tissue-engineering strategies should be adapted in accordance with the system in use. This will afford the means to monitor differential pressure inside a perfusion culture system and, using a range of flow rates, profile the time frame within which pressure becomes harmful. Online monitoring during perfusion culture means that high and low flow rates can be used interchangeably to optimise nutrient delivery to cells within safe pressure limits.

Transmex project results can be used by the scientists and clinicians to develop optimal strategies for tissue regeneration. Achievements in this area will significantly contribute to international health-care system efforts to abate the burden of costly diseases.