Award details

Development of nutritional design for cartilage tissue engineering

Reference	BB/C515004/1
Principal Investigator / Supervisor	Professor Zhanfeng Cui
Co-Investigators / Co-Supervisors	Dr Jill Urban
Institution	University of Oxford
Department	Engineering Science
Funding type	Research
Value (£)	236,793
Status	Completed
Type	Research Grant
Start date	14/11/2005
End date	13/11/2008
Duration	36 months

Abstract

The aim of this project is to develop nutritional design criteria for tissue engineering of cartilage constructs. Cartilage tissue engineering has attracted a lot of effort, but with limited success. One of the key issues in culturing cartilage constructs is nutrient limitation. Under favourable extracellular conditions on nutrients and metabolites, matrix biosynthesis, chondrocyte metabolism and even cell viability may be compromised. Nutrient limitation in engineered cartilage is determined by (a) how fast the nutrient is consumed, which depends on chondrocyte metabolic rate and cell density (b), how fast nutrient can diffuse in, which depends on the hindrance effect of the construct to diffusion (effective diffusivity). The latter depends not only on the initial scaffold design (materials, porosity, tortorsity), but also on cell proliferation and matrix deposition, as well as scaffold degradation. A safe limit, or nutrient design criteria, can be determined based on mathematical analysis on the transient diffusion-reaction process, provided all the necessary model parameters are determined. This project is to develop such a mathematical model and to determine key model parameters. In this project, we will measure the rate of consumption of key nutrients (oxygen, glucose), rate of production of a key metabolite (lactic acid), the rate of ECM (collagen and GAG) production and deposition, of chondrocytes, and relate these rates to nutrient concentrations, medium pH and osmolarity, and concentration of growth factors, hydrostatic pressure (static and dynamic), and scaffold types. We will also determine the effective diffusivities of these key nutrients and metabolites within engineered cartilage constructs and their changes with cell proliferation and ECM deposition. With all the determined parameters, we will be able to develop a mathematical model to describe the distribution of the concentrations of the key nutrients within the 3D engineered cartilage. The model,after experimental validation, can be used to assess whether anywhere within the construct cells are exposed to unfavourable nutrient environment. We aim to provide a user friendly web-based software to perform such an assessment and to provide design criteria for engineered cartilage in terms of size and geometry, scaffold properties such as porosity and tortosity, cell seeding density and distribution, medium composition, use of growth factors and culture conditions. The model framework is modular allowing the introduction of new modules describing additional effects or processes, and can be adopted to assess the engineering of other types of tissues by replacing with appropriate descriptive modules.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	Industrial Biotechnology, Regenerative Biology, Systems Biology, Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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