Thursday, 14 August 2014

Turning up the pressure on bone tissue engineering

Exercise is important for building strong bones, but it is an interesting question as to how bone cells sense these forces and modify the bone structure to cope with increased strain. It has been shown that one of the main ways that cells sense physical activity is through fluctuations in the pressure of the fluid inside the bone and cartilage.

Stress and strain during exercise cause pressure changes that are sensed by osteocytes – cells which live in small, interconnected spaces throughout the bone and act as ‘pressure sensors’ for monitoring bone activity. These then signal to stem cells in the marrow, stimulating them to turn into mature bone cells and replenishing the pool of active cells that are responsible for building bones and healing fractures.

Thus the extremes of intensive training allow athletes to build strength into their bones and compete to their maximum potential, whilst a lack of exercise causes a dramatic weakening of the skeleton. In fact, pressure is sensed by bone cells from an early age - even as the limb is forming in the foetus, a baby’s ‘kicking’ is thought to play a vital role in making sure that the bone and joints form normally by giving them a work-out whilst still in the womb.

At Keele, and in collaboration with Instron (TGT), we have developed a bioreactor which can artificially simulate these natural pressure changes and allow us to experiment on bones in the lab - culturing them in an environment which mimics natural exercise and then accurately measuring the effects on bone growth.

We are now using this bioreactor to look at various aspects of how dynamic pressure affects bone development, using whole (chick) organ cultures and both embryonic and adult bone marrow stem cells. Understanding the role of pressure as a stimulus for bone growth and repair has the potential to dramatically improve clinical treatments for hip and knee replacements, osteoporosis, arthritis and non-healing fractures, helping to translate basic research into advanced medical practice.

In this experiment, femurs from a developing chick foetus were cultured for two weeks in static conditions (top) or with an intermittent pressure (simulating walking) for 1 hour per day (bottom). We found that this significantly increased bone formation in the cortex (*stained red) and caused an increase in the production of collagen (the main organic structural component of bone). We also found that faster frequencies (i.e. faster walking) had the greatest effect on increasing bone density.

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