Infochem - Bone makers
Injuries to, or congenital defects of, the cranial (skull and face) skeleton can leave the bone damaged, beyond repair. In the past surgeons have resorted to metals, such as titanium, to pin bones together, and more recently they have used polymer composites as implants, which come close to bone in strength and mechanical properties. But for facial surgery to be really successful, the implant needs to be made to a precise three dimensional structure so that it complements the person’s skull, thus giving them back their own unique features. Recent advances in the processing of polymers by British and Russian chemists working collaboratively, has not only achieved this, but they have also modified the technology so that biodegradable polymers could be used in the future. The use of such polymers should encourage real bone to grow and thus open up the treatment to young children and babies.
For the past 10 years or so cranial surgeons have been using ‘artificial bone’ as their implant material. This was originally a composite of polyethene (PE), which is well tolerated in the body, together with hydroxyapatite (HA, Ca5(PO4)3OH), a brittle inorganic mineral that makes up most of our bones. The composite behaves like bone in the body because it is chemically similar to natural bone – it is biocompatible. Thus some of the calcium phosphate which is present in HA forms ions and goes into solution. This encourages bone to grow up to the surface of the artificial material unlike metals, which cause bone resorption at their surface. But the real issue for cranial surgeons is that they need implants with very precise shapes.
This was the challenge facing chemist Steven Howdle and his research group at the University of Nottingham, and Russian chemist Vladimir Popov and his team at the Institute of Laser and Information Technologies at the Russian Academy of Sciences in Moscow.
The focus of Howdle’s research is on using supercritical carbon dioxide (scCO2) to process polymers. (Under supercritical conditions – at temperatures above 31°C and pressures 70 times above atmospheric pressure (70Bar, or 7.38MPa) – carbon dioxide is neither liquid nor gas, but has the properties of both. Like a liquid, scCO2 can dissolve a range of solutes, and like a gas it has low viscosity.) Howdle told InfoChem, ‘It turns out that adding scCO2 to a polymer lowers its “melting” point. Normally high temperatures are required to liquify a polymer, and the result is a viscous liquid. Under these conditions it is difficult to mix a solid such as hydroxyapatite into the polymer, but add scCO2 and this process becomes easy at much lower temperatures’.
To reproduce the intricate shapes required for facial implants, the researchers turned to stereolithography – basically drawing with lasers. Surgeons have been using this technology for some time to produce three dimensional images of the skull to help them visualise and plan their operations. The method involves taking an MRI scan or x-ray of the area of the face that requires the implant, and capturing this information in a computer, which then sends it on to a laser stereolithography machine. Howdle explained, ‘By allowing the laser to play on the surface of a bath of liquid monomer, HA and scCO2, under continuous mixing, we could draw the shape of the image. The monomer is converted into solid polymer, only where the laser hits. The base in the bath then moves down a step and the laser draws the next layer and so on until we have a three dimensional model of the image. We then remove the model from the bath and clean it with scCO2, the latter now acting as a solvent to remove toxic residual monomers’.
There are, however, limitations to this method. It can only be used with acrylic monomers (ie derivatives of propenoic acid, CH2=CHCOOH) because these absorb laser light (488nm) and convert to the solid polymer. In addition, acrylic polymers are not the ideal implant material. They are intrinsically toxic, owing to their reactive carbon–carbon double bond, which can lead to inflammation in the body. Despite these drawbacks, precision-shaped implants have been made with composites of PMMA (polymethylmethacrylate, common name Perspex) mixed with HA using this method. These have been used recently to repair the jaw bone of a 15-year old Russian girl (pictured top right before and after the operation).
Howdle and Popov then asked themselves: ‘How can we improve on this? We have an implant that is suitable for use in a 15-year old girl, who has stopped growing, but the piece of plastic, like a metal plate or pin, will be there for the rest of her life. This implant would not be suitable for a younger child who was still growing. The composite would not grow with the child’. The chemists reasoned that if they could make the implant out of a biodegradable polymer, which also contained a growth hormone to stimulate the growth of bone cells, and eventually bone, on and around the implant, as the polymer degraded it would be replaced by real bone.
Just a few months ago, the researchers announced a breakthrough in the processing of such materials (Advanced Materials, in press). They used polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA), two biodegradable polymers used by the medical industries in disposable stitches and drug delivery systems.
They couldn’t, however, use laser stereolithography because biodegradable polymers do not absorb laser light. Instead they used a laser sintering technique. Howdle explained, ‘We figured out that if we were to put something else on the surface of these polymers which did absorb laser light, when the laser plays over the surface, these particles should absorb enough heat to melt the surface of the polymer particles and fuse them together. This would have the added advantage that drugs could be mixed in with the polymer’.
In an experiment, the chemists made up the polymer – PLA mixed with growth hormone and a surface coating of carbon. Supercritical CO2 was used to mix together the three ingredients, and to clean the polymer at the end. They then laid down a thin layer of powdered polymer and, using the computer-linked laser machine, played the laser over the polymer as directed by the shape of the required implant. The carbon particles absorbed laser light enough to melt the surface of the polymer, fusing the polymer together. Loose powder was swept off, an elevator moves up, and the process repeated until a three dimensional model was made.
The next step will be to make real implants to transfer into patients. A few years down the line such biodegradable implants with specific shapes could be used in patients who are still growing, and who will end up with natural bone in their bodies rather than plastic.
Kathryn Roberts
