Projects

Project HT1 - Cell monitoring techniques for tissue engineered product quality (TE product quality)

Background

Tissue engineering is an emerging healthcare technology for regenerating, repairing or replacing damaged tissue and is at the centre of emerging approaches of regenerative medicine. As with any pioneering new technology regulation is critical for product quality, safety and development.

Currently there are no unified regulatory controls for tissue engineered products as they challenge the existing formal regulatory provisions and the wider governance environment of current regulatory classifications (medical devices, medicinal products and biologics). Under new regulations to be enforced from 2007 the majority, if not all, tissue engineered products are likely to fall under the proposed Advanced Therapy Medicinal Products (ATMP) Regulation. However, there remain differing opinions as to the scope of the Regulation when considering the potential pharmaceutical action of the cellular material within related products, a problem increased by difficulties in measuring cell quality. Tissue engineering companies supported by their trade associations (Association of British Healthcare Industries [ABHI] and its European counter part, Eucomed) have defined common priority issues that impact directly on monitoring product quality and that require innovative measurement solutions.

Almost all tissue engineered products incorporate a scaffold or biomaterial designed to mimic extracellular matrix (ECM) and support viability of cells specific for the tissue to be replaced. Even in the simplest model these two factors, which underpin product performance, are difficult to measure. As products become more complex and require cell proliferation/differentiation within the ECM or remodelling of the ECM by the cells, these measurement problems become even greater. Added to this are problems associated with maintenance of cellular efficacy throughout the ‘shelf life’ of such products. To address these issues, companies are increasingly looking for assurance as to the fitness for purpose of innovative methods for assessing the intrinsic variability in the active cellular component of the product and for characterising product quality.

This project will develop a model of a tissue engineered for the evaluation of measurement techniques monitoring the cell and ECM in a controlled and reproducible manner. The model will be extended by testing the robustness of the measurement techniques in both a complex representation of, and a commercial clinical, tissue engineered product.

Aims and objectives

The overall aim is to develop and validate techniques for monitoring cells in a scaffold through:

• Development of an industrially relevant model of a tissue engineered product using a well characterised industrially appropriate cell line and defined ECM system.
• Evaluation of robust and reliable methods for measuring parameters associated with cell quality in a defined ECM system.
• Determination of the suitability of emergent imaging techniques (such as MALDI imaging) for measuring protein composition in defined protein matrix systems.
• Evaluation of robust and reliable methods for measuring cell quality in a tissue engineered product model following short term storage.
• Assessment of ‘fitness for purpose’ of cell and matrix monitoring techniques using a clinically appropriate tissue engineered product.

Project outputs

• A poster entitled: ‘The use of stress markers to inform on tissue engineered product quality’ was presented at the World Conference on Regenerative Medicine held in Leipzig in October 2009.
• A presentation entitled ‘The use of stress markers to inform on tissue engineered product quality’ was presented at the 2009 World Conference on Regenerative Medicine.
• Publication of a case study entitled: 'Life through a lens; novel quantitative cell imaging'.

Further information can be obtained by contacting the NMS helpdesk at LGC.