New concepts in the 3-dimensional nature of blood flow improving the treatment of people with peripheral vascular disease and requiring haemodialysis.
Submitting InstitutionUniversity of Dundee
Unit of AssessmentGeneral Engineering
Summary Impact TypeTechnological
Research Subject Area(s)
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Medical Physiology
Summary of the impact
Commercialisation: Through government grants, institutional and
private investors, a medical devices company (Vascular Flow Technologies)
Products: Spiral Laminar Flow™ Vascular Grafts for use in bypass
for peripheral arterial disease and vascular access for haemodialysis.
Market / Sales: Spiral Laminar Flow™ Grafts are sold in 18
countries, with over 3000 grafts implanted (<1% estimated market size)
and sales in excess of £1million.
Patient Outcomes: Published and presented clinical series show the
grafts have increased survival rates leading to reduced re-interventions
and reduced amputations.
Previously the understanding of blood flow within the body has revolved
around a 2-dimensional representation of flow within rigid vessels.
Following work visualizing the internal structure of medium sized
arteries, a hypothesis was developed by one of the principal
investigators, Professor Stonebridge: that there is a rotational element
to laminar flow with its axis at the centre of the artery.
Together with subsequent work, it is possible to bring left ventricular
anatomy and function together with blood flow within large to medium
arteries, as a coherent beneficial spiral laminar flow system [1-3].
Vascular grafts which generate a normal non-turbulent vascular flow
environment for blood vessels and their cell lining — stable spiral
laminar flow — have significant advantages over all other grafts which
generate a damaging turbulent outflow.
The next stages of the project, engineering and product development, were
carried out by Professor Stonebridge and Professor Houston with colleagues
in engineering. This required two key inter-related innovations. The first
was to develop a non-invasive, reproducible method of identifying spiral
laminar flow in vivo and as part of device assessment. This has been
achieved using 2 modalities; colour-Doppler ultrasound and Magnetic
Resonance Imaging (MRI) [1-2]. This has confirmed that normal blood flow
is spiral laminar in nature and has allowed the design and testing of a
new family of prosthetic bypass grafts [1-3,5]. Such grafts are used to
treat diseases such as peripheral arterial disease and renal failure (see
section 4 for more information).
The second was to begin to define the advantages of such a flow pattern
using engineering techniques of computational fluid dynamics, bench
testing and clinical studies [4-5]. This initially examined spiral and
non-spiral laminar flow through a narrowed conduit. This indicated that
rotational laminar flow induced `laminar stability' in a flow environment
that would otherwise induce turbulence . Clinical studies revealed an
association between the absence of spiral laminar flow and the severity
and progression of disease .
The next stage was to design and engineer a prosthetic graft that induced
a flow profile within manufactured devices identical to that seen in
healthy arteries. This required multiple iterations of a three part
approach to design and pre-production prototype testing; computational
fluid dynamics, flow bench testing (requiring the development of a
patented flow pump), and pre-clinical animal testing in modelling
peripheral vascular and high-flow arterio-venous flow environments. This
required the development of a pre-clinical model with flows matching
intended human flow rates. The subsequent spiral flow inducer is protected
by 18 families of patents ranging from broad concept patents to the grafts
critical geometries. Finally the prototype was engineered using a
composite material design to allow commercial production and regulatory
approval in the EU and US for product marketing and sales.
References to the research
Peer reviewed publications: (Three key references are denoted with
1. *In vivo spiral laminar flow. Stonebridge PA, Hoskins P, Allan
PL, Belch JJF. Clinical Science 1996; 91: 17-21
2. *2-Dimensional Flow Quantitative MRI of Aortic Arch Blood Flow
Patterns: Effect of Age, Gender and Presence of Carotid Atheromatous
Disease on the Prevalence of Spiral Blood Flow. Houston JG, Gandy SJ,
Sheppard DG, Dick JBC, Belch JJF, Stonebridge PA. J. Magn. Reson. Imaging
2003; 18(2):169-74. DOI: 10.1002/jmri.10341
3. Three-dimensional blood flow dynamics: spiral/helical laminar flow.
Stonebridge PA. Methodist Debakey Cardiovasc J. 2011 Jan-Mar;7(1):21-6.
4. *Non spiral and spiral (helical) flow patterns in stenoses. In vitro
observations using spin and gradient echo magnetic resonance imaging (MRI)
and computational fluid dynamic modelling. Stonebridge PA, Buckley C,
Thompson A, Dick J, Hunter G, Chudek JA, Houston JG, Belch JJ. Int Angiol.
5. Spiral laminar flow in the abdominal aorta: A predictor of renal
impairment deterioration in patients with renal artery stenosis? Houston
JG, Gandy SJ, Milne W, Dick JB, Belch JJ, Stonebridge PA. Nephrol Dial
Transplant. 2004 Jul;19(7):1786-91. DOI:10.1093/ndt/gfh238
a. SUPA/SINAPSE PhD Studentships 2010, £56,000. Fluid dynamics assessment
of spiral flow inducing intravascular stents.
b. DPFS MRC 2010 £296,632. Extracorpeal system for pulsatile flow and
respiratory motion of Thiel embalmed human cadavers "Dundee Pulsatile Flow
c. Knowledge Transfer Partnership 2010, £142,292. Development of new
arterial graft and stent design based on improved materials & tests
prototypes & products using imaging blood flow measurement capability.
There are 54 granted patents related to spiral flow and its testing
within 18 Patent Families in Europe, USA, China, Japan, India, Taiwan, and
Details of the impact
Peripheral arterial disease is a narrowing of the arteries causing
reduced blood flow. Symptoms range from leg pain when exercising to severe
foot pain, ulceration and gangrene with significant potential for limb
amputation and affects 10.5m individuals across Europe and North America.
One of the main treatment options replaces the diseased artery with a
synthetic peripheral vascular graft (PVG).
Haemodialysis (HD) is a common treatment for patients with end stage
renal failure. Over a quarter of a million patients receive haemodialysis
in Europe, increasing at a rate of 5% per year (European Renal Association
— European Dialysis and Transplant Association Registry 2009). One method
of establishing access to the patients' circulation required for
hemodialysis is arteriovenous graft (AVG) implantation.
The durability of all prosthetic PVG or AVG are severely limited by the
formation of blood vessel narrowing (stenosis) due to post-procedural
overgrowth of vessel wall cells (intimal hyperplasia). Forty to 70% of PVG
used below the groin fail within 2 years leading to prolonged hospital
stays, repeated interventions, and amputation. Sixty to 80% of AVG fail at
one year, resulting in poor dialysis, multiple re-interventions and loss
of dialysis access.
From the research carried out by Stonebridge and Houston, the creation of
vascular devices which engender spiral laminar flow were expected to
improve graft patency and reduce disease progression [REFa]. This led to
the start up of a company to design, market and sell such devices.
Creation of a new bioengineering design company globally marketing
vascular medical devices:
In 2001 Vascular Flow Technologies Ltd was founded by Profs P.
Stonebridge and G Houston, and Dr J Dick. The aim was to create an
international, innovative medical device company and to explore
non-medical/industrial applications of spiral laminar flow as a platform
technology. Tayside Flow Technologies Ltd, renamed Vascular Flow
Technologies Ltd (VFT) is currently a SME based in Dundee, Cambridge and
Boston (Mass., USA), employing 15 full-time staff and a further 4
part-time consultants [REFb].
The company has attracted £13.5million of external investment (including
£950k of government and industry grant funding (SMART and SpurPlus)).
Recent investment in 2013 (£1.5million) underpins more rapid penetration
of the US market [REFc]. Out licensing of the core IP within a number of
areas is also in progress. This will increase the product portfolio and
significantly expand the company's potential market.
Vascular Flow Technologies currently has 2 established vascular graft
product ranges (6mm and 8mm SLF™ peripheral vascular graft and a 6mm SLF™
arteriovenous vascular access graft) with regulatory approval in Europe
(`CE mark' issued by Intertek) and the USA (`510k substantial equivalence'
issued by the FDA) between 2007 and 2010 (Table) [REFd]
Table: EU and USA regulatory approval
|PV 6mm / 8mm
|PV 6mm /8mm
The products have been manufactured by an OEM (original equipment
manufacturer); Vascutek, Renfrewshire, Scotland (a Terumo Company) since
2008. Blank expanded polytetrafluoroethylene (ePTFE) grafts are
post-processed to add a precisely engineered, patented spiral induction
segment to the distal end of the graft (Figure above).
The European Market for Peripheral Vascular Grafts is valued at
$100.2million with growth expected to increase at a compound annual rate
of 7.3%. The grafts are marketed and distributed from Scotland. Vascular
Flow Technologies established distribution networks in USA and Europe,
South East Asia, and Japan between 2008 and 2013. Over 2500 grafts have
been implanted worldwide in 18 countries (Australia, Austria, Belgium,
Czech Republic, Denmark, Germany, Greece, Italy, Netherlands, New Zealand,
Russia, Saudi Arabia, Spain, Switzerland, Thailand, Turkey, UK, and the
USA). Further regulatory approval has been obtained in France and been
submitted in Japan [REFb, REFc].
Vascular Flow Technologies has also entered into a unique regional
partnership with a multinational vascular devices company, LeMaitre GmbH,
as distributor of Spiral Flow vascular Grafts, initially, in Germany
reinforcing industry recognition and impact of this new technology [REFe].
Sales within the REF period, to the end of 2012, of the graft products
are in excess of £1million [REFc].
Improved patient care:
Published and presented clinical series show Spiral Laminar Flow ™ grafts
have increased graft survival leading to reduced re-interventions and
reduced amputations [REFf, REFg]. Patient registry/clinical trials are
ongoing with an EU grant (€2.6million) being offered to examine the
clinical trends in haemodialysis patients including assessment of the
impact of the VFT graft [REFh]. Other companies have begun to adopt the
underlying principles in their medical device products [REFi].
Vascular Flow Technologies technology, based in the UK with UK
manufactured products, has delivered a significant new platform technology
applicable to medical devices to a global market.
Sources to corroborate the impact
[REFa] Adaptable technology is crucial in accommodating a variety of
patient needs. Professor Alan Lumsden, Methodist DeBakey Hospital Houston.
[REFb] Vascular Flow Technologies Ltd. (VFT) www.vascular-flow.com
[REFc] Factual statement: CEO, Vascular Flow Technologies.
[REFd] NHS National Institute of Health Research. Spiral laminar flow
peripheral bypass graft for PAOD. NIHR Horizon Scanning Centre, School of
Health & Population Sciences, University of Birmingham. Sept 2009 http://www.hsc.nihr.ac.uk/topics/spiral-laminar-flow-peripheral-bypass-graft-for-pe/
[REFe] LeMaitre New Distributor in Germany. http://www.vascular-flow.com/new-distributor-in-germany/
[REFf] Spiral Flow™ Grafts Offer Superior Clinical Outcomes in Prosthetic
Bypass Grafting. Veith Symposium in New York, USA. http://www.prnewswire.com/news-releases/spiral-flowtm-grafts-offer-superior-clinical-outcomes-in-prosthetic-bypass-grafting-180145491.html
[REFg] Spiral laminar flow prosthetic bypass graft: medium-term patency
from a structured first-in-man structured registry study. Stonebridge PA,
Vermassen F, Dick J, Belch JJ, Houston G. Ann Vasc Surg 2012;
[REFh] EU IAAP Grant Offer €2.3million — PIAP-GA-2012-324487 ReDVA:
Development of hemodynamic solutions in Renal Dialysis Venous Access
[REFi] BioMinics 3D™ Stent for peripheral artery disease.