Synthetic blood vessels in the offing

The fact that blood's not only thicker than water, but biologically "sticky", creates problems for cardiovascular surgeons replacing blocked coronary arteries.

Synthetic polymer blood vessels lack the 'compliance', or radial elasticity, that allows natural arteries expand and contract with blood pressure changes as the heart beats. At smaller diameters, blood flow slows, and the risk of clotting rises.

Melbourne biomedical-device developer Kryocor's solution - conceived by an inventive Melbourne cardiovascular surgeon - is to use nature's own ready-made, compliant biopolymer, collagen, as a starting material for 'naturalised' blood vessels.

Kryocor began life as a dedicated R&D subsidiary of Melbourne biotech BioNova, but was then spun off to commercialise novel processes for turning natural collagen scaffolds into replacement blood vessels and prosthetic implants.

The company's Flonova implants, developed to bypass blocked blood vessels in the legs, are made by turning natural 'biotubes', such as cattle ureters, into immunologically neutral scaffolds.

The Flonova medium-diameter blood-vessel implants were extensively tested in animals before being used in humans.

McMcCormack said some of the original patients with blocked leg arteries who had faced the prospect of amputation five years ago are still walking around normally after receiving the implants. The product has been registered by the Therapeutic Goods Administration.

Kryocor hopes to out-licence the technology this year for blood vessels in the 6-10mm diameter range. It does not intend to manufacture them itself - "We're a technology developer, not a marketer," McCormack said.

With market for large-diameter (10-25mm) blood vessels already well served by implants made from Dacron or other synthetic polymers, the company is now working on small-diameter (3-5mm) blood vessels. They will be used in the application envisaged by the cardiovascular surgeon who had the original idea: replacement coronary arteries.

For coronary artery bypass applications, the treated collagen tubes are bathed in culture medium populated with the patient's own endothelial cells, which normally line the blood vessels.

The cells colonise the interior of the collagen tube, forming a smooth surface over which blood flows easily. Immune-system cells in the blood recognise the cellular lining as "self" when it is surgically implanted to restore blood to ailing heart muscle.

McCormack said that, at this diameter, there is currently no real alternative to the patient's own blood vessels. Even relatively flexible polymer tubes made with super-slick Teflon also become clogged.

The common practice of harvesting blood vessels from elsewhere in the patient's system is problematic because of the need to find enough vessels for multiple bypass surgery - if the surgeon cannot find a suitable blood vessel, he is 'stuck'.

Kryocor has begun animal trials of the small-diameter implants. Nobody yet makes such a product, and the US and European markets for coronary artery bypass grafts are estimated at US$2.8 billion - four times larger than the US$690 million market for larger-diameter implants.

Kryocor hopes to have its coronary artery bypass implant ready for commercialisation in two years.

McCormack said the compliance of the collagen tubes lies somewhere between that of a natural blood vessel and the inflexibility of a polymer like Dacron. The collagen-treatment process can also be used to create 3-dimensional structures, with or without a living coating of the patient's own cells for biocompatibility.

Kryocor is developing a collagen-based anterior cruciate ligament (ACL) implant. The market for replacement anterior cruciate ligaments - the classic football/basketball injury - is estimated at US$2 billion worldwide, and the company expects to have a prototype by 2007.

"We expect to be the first company in the world to address these markets," McCormack said. "We aim to be as highly regarded in our field as Cochlear and Resmed are in theirs".

Carbon fibre has great tensile strength as a replacement for ruptured anterior cruciate ligaments, and produces a very stable knee, but it eventually wears out or can snap under stress, requiring full replacement.

The big advantages of the collagen prostheses, he said, is that they are not subject to rejection, and can become self-regenerating when colonised by the patient's own tissues.