Repairing cracks and holes in bones could be made much easier thanks to a finding that reduces the viscosity of bone cement. By using sodium citrate as a liquefier, clinical calcium phosphate can be altered from a toothpaste-like consistency into a creamy liquid that thickens with time. This means that more cement powder can be added, which in turn reduces the water content making a much stronger cement. Another advantage of this cement lies in the ease of its delivery, as the less viscous cement can be delivered through a needle allowing access to previously inaccessible areas.
Cement liquefiers are common among civil engineering applications, but using sodium citrate as a liquefier for clinical cement is both novel and non-toxic, which addresses the fundamental challenge of biomaterials - getting new properties from a limited pool of acceptable materials and chemicals.
To illustrate the strength of the resulting material, its developers Dr. Jake Barralet and Liam Grover at the University of Birmingham Dental School, UK, along with collaborators Dr Uwe Gbureck and Professor Roger Thull from the University of Wurzburg stood on a cylinder of the concrete measuring only 6mm in diameter. It supported them easily.
The Effect of Sodium Citrate Addition
Barralet’s team started work on this development around 12 months ago armed with the knowledge that citric acid was used already in low concentrations as a retardant in apatite cements. ‘It has been claimed by previous researchers that this improves injectability - but these authors were referring to ejection from a 2mm diameter nozzle, not a 800 micron hypodermic needle. This is an important distinction to make because the ejection pressure is related to the fourth power of (1/diameter), so reducing the diameter by 2.5 times, as we did, would increase the pressure required to eject it by around 40 times. In fact it couldn’t be done and the needle kept getting blocked as at that pressure the liquid and solid in the cement separate, so the needle acts as a quick blocking filter,’ says Barralet.
The Effect of Reducing Pore Size
Barralet’s solution relies on an elegantly simple method of decreasing the pore size of calcium phosphate using trisodium citrate or citric acid. The trisodiurn citrate decreases interparticulate forces by means of an electrostatic mutual repulsion, which allows a reduction in the amount of pores in the sample - meaning a denser packing of particles and a stronger material. Results so far show that calcium phosphate modified in this way is up to 400% stronger that cement mixed with water. Results for trisodium citrate and citric acid gave compressive stresses of 153MPa and 116MPa respectively (using a compaction pressure of 50MPa), which shows an ideal replacement for cortical bone that has compressive stresses around the 100MPa mark.
‘Our finding was that sodium citrate was required for apatite cements, and that much higher concentrations of up to 0.5 molar were needed than had been used before. Citric acid and not sodium citrate is needed to get this effect in brushite cements.’
One area that this modified cement could open up is in vertebroplasty which would need injectable material forming into a high strength composite to withstand the compressive forces of the spinal vertebrae.
Other areas that could benefit from cement with increased strength and lower viscosity include:
• Craniofacial distraction - the team is working with researchers at Birmingham Children’s Hospital at expanding applications in this field that works to correct disorders such as obstructive sleep apnoea
• Anchor points - cortical bone screws can be held in the cement so it could be used to create surgical anchor points
• Fixation - since the cement is strong enough to be drilled through it may be used in conjunction with fixation hardware
• Minimally invasive procedures - injectable formulations could be used to simplify procedures such as sinus floor augmentation
• Pre-sets - such as a porous block made without sintering. Drugs could also be incorporated.
‘Being non-toxic, alpha hydroxy acid and salts may find other applications in stabilising mixtures such as slurries and liquefying pastes ceramics and cement industries,’ says Barralet. The team is now researching other applications and looking for a licensing partner and / or funds to proceed towards clinical trials.