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Queen Mary University of LondonQueen Mary University of London
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School of Engineering and Materials Science
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PhD Thesis: The influence of tensile strain on fibroblasts in culture.

Author: BERRY, Catherine

Year: 2002

Supervisor(s): David Lee, Julia Shelton

The poor healing capacity of the human anterior cruciate ligament and relative lack of success of surgical repair and/or reconstruction has prompted development of the Bio-ACL, a biodegradable poly-L-lactic acid braided scaffold infused with a human dermal fibroblast seeded collagen gel, with the aim of producing a neo-ligament. Mobilisation regimens are known to influence ligament healing, thus application of mechanical load to cell seeded collagen gel constructs may improve implant repair potential.

There are two potential sources of cells for such a device; adult and neonatal human dermal fibroblasts, representing autologous and allogenic cells respectively. This thesis initially addressed the biological response of applied load to such cells in monolayer. This was performed using two systems, the commercially available Flexercell system and a novel cell straining capable of applying uniaxial cyclic strain.

The more active cell type, with regards to cell proliferation, matrix synthesis and cell alignment, was subsequently seeded into four individually developed collagen gel models. The models were either pegged, providing an internal stress field, or free floating, stress relaxed. Cell-mediated collagen gel contraction over five days produced a dense connective tissue-like matrix in each model and studies, investigating cell/collagen alignment and matrix metalloproteinase production, compared the effects of the varied states of tension induced by gel contraction in each model.

The final developed biologically relevant gel model consisted of viable, uniaxially aligned cells and collagen fibrils and was conclusively used in the aforementioned cell straining system adapted for three-dimensional use. The effect of 10% cyclic uniaxial strain on the cell seeded model was investigated.