Rapid ‘dip and dry’ technology for improved biomaterials
12 January 2011
Sheffield-based researchers have developed a simple, generic platform for altering the surface properties of bioactive materials. Their findings could lead to improved medical implants and devices that can prevent localised inflammation at the implantation site, as well as a wider range of bioactive materials with anti-infection properties - such as contact lenses and even fridges.
Many implantable medical devices can trigger an acute inflammatory response, which in turn can be detrimental to the function of the device, such as stress cracking of pacemakers or a re-narrowing of coronary arteries following a stent implant (see 'Treating heart disease today' below). This can be triggered either by the initial implantation injury or by the biomaterial itself. Inflammation can be treated with steroids or non-steroidal anti-inflammatories (NSAIDS). However, these drugs frequently lack sensitivity or a specific targeted site of action, which can lead to side effects.
John Haycock. Image courtesy of the University of Sheffield.
Bioengineer Dr John Haycock from the Kroto Research Institute and Dr Nick Williams from the Department of Chemistry at the University of Sheffield have been looking to develop more specific and localised forms of treatment to control inflammation associated with biomaterials. Funded by BBSRC and the Engineering and Physical Sciences Research Council, the Sheffield team has developed a new method for generating model surfaces with bioactive anti-inflammatory properties.
Making things stick
Using similar technology to that used to create fingerprint repelling (oleophobic) touch screens for the latest mobile phones, Haycock and Williams coated a model surface (a glass plate) by dipping it into a solution containing a glue-like material (an organic compound called resorcinarene) bonded to a short peptide with known anti-inflammatory properties (a synthetic version of melanocyte-stimulating hormone, MSH).
"Resorcinarenes form coatings on a wide variety of materials and previous work in Sheffield showed that they could be used to make hydrophilic surfaces," says Haycock. "Our study provides proof of concept that this 'dip and dry' approach can also be used to develop anti-inflammatory coatings."
The team began by creating a synthetic version of MSH, and evaluating its anti-inflammatory signalling properties when attached to a chemical 'tether'. "We were able to show that a short synthetic peptide sequence, glycine-lysine-proline-D-valine (GKP-D-V), retained its anti-inflammatory properties most effectively when attached to a PEG350 tether.
"Our study provides proof of concept that this 'dip and dry' approach can also be used to develop anti-inflammatory coatings."
According to Haycock, one of the benefits of using GKP-D-V is that its short peptide sequence makes it highly amenable for synthesis at both the laboratory and commercial scale. "It would be relatively cheap to manufacture," he says.
"What we now have is a generic platform for altering the surface properties of biomaterials and medical devices," says Williams. "The properties of the coating can be changed simply by changing the nature of the group that is covalently linked to the resorcinarene."
As it turns out, the team also discovered that their tethered GKP-D-V peptide also has antimicrobial properties. Which leads them to postulate that another application of this platform could be for screening candidate drugs in the form of a lab on a chip.
According to the British Heart Foundation, coronary heart disease accounts for approximately one in five deaths in men and one in six deaths in women each year (ref 1).
New technologies have dramatically improved the treatment of this disease over recent years. Over 73,000 angioplasties – where a balloon is inflated via a catheter to unblock coronary arteries – are now carried out annually in the UK, and this number is increasing at a rate of 5% per year. Compared to open heart surgery, recovery from an angioplasty is quicker, but the procedure is not problem free as the healing process can, in itself, lead to restenosis – re-clogging of the artery due to the growth of cells at the treatment site.
The use of a bare-metal ‘stent’ (a small tubular scaffold that is inserted into the artery) reduces the risk from restenosis. ‘Drug-eluting’ stents (DESs), which are coated with drugs to stop vascular cells from dividing, reduce this risk further still. However, the use of DESs can increase the risk from late stent thrombosis, probably due to delayed healing – a side effect of the use of anti-proliferative drugs (ref 2).
Generation of bioactive materials with rapid self-assembling resorcinarene peptides. doi: 10.1002/adma.200802731
- British Heart Foundation (BHF) statistics website (external link)
- BHF Managing patients with coronary stents Factfile No. 3, May 2008
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