Background

In fixation of the fibula in ankle fractures, AO advocate using a lag screw and one-third tubular neutralisation plate for simple patterns. Where a lag screw cannot be placed, bridging fixation is required. A local pilot service evaluation previously identified variance in use of locking plates in all patterns with significant cost implications. The FAIR study aimed to evaluate current practice and implant use across the United Kingdom (UK) and review outcomes and complication rates between different fibula fixation methods.

Human mesenchymal stem cells (hMSCs) have the capacity to differentiate into adipocytes, chondrocytes, or osteoblasts, and are an exciting tool to be used in regenerative medicine and surgery. By manipulating the surface structure and physical properties of a biomaterial on which hMSCs can be incorporated, the biological response of these cells at the implant site can be controlled. Whilst both topography and surface stiffness are known to influence differentiation of hMSC's, little is understood of the molecular mechanisms that underpin these responses. In this study we use immunofluorescence and confocal microscopy techniques to assess the change in both the abundance and the distribution of H3K9me2 or H3K9ac patterns in hMSCs cultured on materials with controlled topography and stiffness, under basal and osteogenic conditions. These data demonstrate that levels and localisation of both H3K9me2 and H3K9ac alter in hMSCs cultured on the different substrates and that these surfaces dictate the response to osteogenic stimuli, suggesting that the control of cytoskeletal structure can be linked to chromatin activity. This regulation of histone modification by MSC interaction with the surrounding scaffold provides not only a mechanistic link to the control of cell fate but also the opportunity to design biomaterials that better influence cell activity.

hMSC cultures were prepared from osteoarthritic patients. Silicone elastomer (PDMS) culture surfaces of varying degrees of stiffness (1:10, 1:30 and 1:50 PDMS, tissue culture plastic and glass) were investigated in isolation and in combination with differentiation media. CD marker expressions of ‘stemness’ were investigated. RNA expression changes in OA-hMSCs and non-OA-hMSCs were also investigated for a panel of genes (inclusive of ‘stemness-’ and osteogenic-linked genes, FKBP5 and osteomodulin).