A team of researchers at the London's Royal Free Hospital have received an $800,000 (£500,000) grant to take their invention of an artificial artery from the laboratory to human clinical trials within the next year. London's Royal Free Hospital used nanotechnology to develop the small bypass graft from a polymer material. The material enables the graft to mimic the natural pulsing of human blood vessels, which enables them to deliver nutrients to the body's tissues.
Image Credit: Royal Free Hospital, London
The grant from the Wellcome Trust means the team, led by George Hamilton, Professor of vascular surgery, and Alexander Seifalian, Professor of nanotechnology and tissue repair, is one step closer to making their invention available to thousands of patients with vascular disease.
The team has developed a small diameter bypass graft made from a polymer material modified by nanotechnology, for use in coronary artery and lower limb arterial surgery. The material enables the graft to mimic the natural pulsing of a human blood vessel such as arteries delivering blood and nutrients from the heart to every cell, organ and muscle in the body.
The wall of the artery is designed to be able to withstand blood pressure throughout a person’s lifetime and is normally very strong. If it is damaged by disease such as arteriosclerosis or hardening of the arteries, the artery can become blocked, or in some patients the wall can weaken becoming an aneurysm, and it may rupture.
The current surgical treatment is to bypass or replace the damaged vessel using a plastic graft or preferably a vein taken from the patient’s own leg, but many patients do not have suitable veins.
These plastic grafts were originally made with the same nylon used to make ‘drip-dry’ shirts (Dacron), or PTFE a type of plastic noted for its non-stick properties. This type of material is suitable for larger grafts but has poor results for smaller grafts of less than 8mm, used for instance in heart bypasses. This is because these materials cannot pulse and their surfaces stimulate clotting of the blood in the graft.
Prof Hamilton said: "There is a high failure rate using these rigid small diameter bypass grafts. Many patients who have needed smaller bypass grafts but have not had suitable veins, have had limbs amputated and some patients unable to have coronary bypass surgery have had heart attacks and died.”
He added: “Led by Professor Seifalian, we have used nanotechnology to develop this material to mimic as closely as possible the natural artery. Nanotechnology involves incorporating single microscopic molecules that have important effects on the circulation into the graft material.”
“The new micro-graft pulses rhythmically to match the beat of the heart. As well as this, the new graft material is strong, flexible, resistant to blood clotting and doesn’t break down - which is a major breakthrough.”
The team also found that coating the inner lining of the new graft material with certain molecules by nano-technology, stimulated circulatory endothelial stem cells to line the graft. These cells, known for their ability to renew themselves, can help to repair the damaged blood vessel even further.
Prof Hamilton said: “This will be hugely beneficial to patients in the NHS as we will be able to reduce heart attacks, reduce amputations and ultimately save lives.”
In the long-term, Professors Hamilton and Seifalian and their team hope to develop a range of grafts, stents and devices immediately available ‘off the shelf’ to all cardiac and vascular surgeons to more successfully treat heart and blood vessel disease. The next phase of the research is due to go to clinical trials at the end of 2010.
Professor Hamilton with the artificial artery
Image Credit: Royal Free Hospital, London
The ultimate aim is to use the graft in coronary artery and lower-limb arterial surgery, which doctors say could reduce amputations and heart attacks.
The ultimate aim is to use the graft in coronary artery and lower-limb arterial surgery, which doctors say could reduce amputations and heart attacks.
The underlying nanotechnology used to create the artificial artery is available for licensing from the University College of London. The novel nanocomposite polymer (NC) can uniquely achieve complete tissue and blood compatibility, unlike conventional medical polymers such as PTFE and Dacron. This offers exciting possibilities for medical device manufacturers.
The technology and its advantages:
The nanocomposite is based on Silsesquioxane, and exhibits unique surface properties. It preferentially adsorbs and deactivates fibrinogen, thus preventing activation of the coagulation cascades, inflammation and growth of tissue capsule.
A new synthesis route allows preparation of the NC so that it has controlled properties. This is achieved by introducing Silsequioxanes as pendant groups into the backbone of the polymer. Uniquely there is no degradation by hydrolysis or oxidation. However, variants of the NC can also be produced so that controlled degradation will occur, making these variants suitable candidates for tissue engineering scaffolds. In addition the NC can be manipulated, for example by attachment of drugs, gene vectors or other biomolecules relevant to the applications.
The NC is not toxic to cells and supports the adhesion and growth of cells in vitro. Furthermore, the NC inhibits protein absorption by prolonging the coagulation time. This prevents thrombogenicity and non-compatibility with blood, which together are the second principal reason behind failure of material surfaces of medical devices.
A three-year in vivo implantation study in a large animal model has confirmed in vitro findings that the NC is biocompatible, non-toxic, and shows no evidence of degradation, inflammation or capsule formation. As the NC is not drug based, CE and FDA approval are more easily achievable and so offer the device manufacturer unique opportunities.
A new synthesis route allows preparation of the NC so that it has controlled properties. This is achieved by introducing Silsequioxanes as pendant groups into the backbone of the polymer. Uniquely there is no degradation by hydrolysis or oxidation. However, variants of the NC can also be produced so that controlled degradation will occur, making these variants suitable candidates for tissue engineering scaffolds. In addition the NC can be manipulated, for example by attachment of drugs, gene vectors or other biomolecules relevant to the applications.
The NC is not toxic to cells and supports the adhesion and growth of cells in vitro. Furthermore, the NC inhibits protein absorption by prolonging the coagulation time. This prevents thrombogenicity and non-compatibility with blood, which together are the second principal reason behind failure of material surfaces of medical devices.
A three-year in vivo implantation study in a large animal model has confirmed in vitro findings that the NC is biocompatible, non-toxic, and shows no evidence of degradation, inflammation or capsule formation. As the NC is not drug based, CE and FDA approval are more easily achievable and so offer the device manufacturer unique opportunities.
Market opportunity:
The physical properties of the NC are such that it can be tailored to many specific medical device applications, for example:
• Coronary artery bypass grafts – the NC can be made more elastic to closely mimic the elasticity of arteries
• Coating of coronary stents – the NC supports the adhesion and growth of cells, including endothelial cells
• Tissue scaffolds – the NC can be tailor-made to be degradable under controlled conditions
• Condoms and surgical gloves – the NC is thin and strong and retains its original shape
The NC will allow manufacturers to market a broad spectrum of safer, more efficient medical devices and other products.
• Coronary artery bypass grafts – the NC can be made more elastic to closely mimic the elasticity of arteries
• Coating of coronary stents – the NC supports the adhesion and growth of cells, including endothelial cells
• Tissue scaffolds – the NC can be tailor-made to be degradable under controlled conditions
• Condoms and surgical gloves – the NC is thin and strong and retains its original shape
The NC will allow manufacturers to market a broad spectrum of safer, more efficient medical devices and other products.
Reference number: 94-092
Status PCT Application has been filed, priority date 20th January 2004, Application Number PCT/GB05/000189
Availability Exclusive and non exclusive licensing opportunities
For information on licensing, contact:
Karen Cheetham, UCL Business PLC
T +44 (0)20 7679 9000, Email: k.cheetham(at)uclb.com
