Commercialisation of University Research
Professor Timothy McGloughlin and Dr Michael Walsh of the University of Limerick chart the development path of a novel graft for vascular and artero-venous access applications.
The year 2010 will long be remembered in Ireland as a gloomy year in terms of the national economy, with large increases in unemployment and a return of emigration. In this article, Professor McGloughlin presents a more positive picture of Ireland, which is now the largest exporter of medical devices in Europe. Exports in 2009 were more than €6.9 billion and this figure is likely to be exceeded for 2010.
Against this backdrop of a highly successful medical device industry, Irish government policy remains strongly committed to the enhancement and development of this important sector. It supports research and development in multinational, indigenous and start-up companies and in the higher education institutions throughout Ireland. The extent of this support is reflected in the wealth of high quality research programmes that are available to support academic and company research and in novation. The state agencies Enterprise Ireland (www.enterprise-ireland.com
), Science Foundation Ireland (www.sfi.ie)
, the Industrial Development Authority (www.idaireland.com
), and the Health Research Board (www.hrb.ie
) have all committed large investments over recent years and continued investment was recently announced for 2011. This article describes the process by which academic research at the University of Limerick is being developed for commercialisation in this fast growing and dynamic industrial sector.
A case study
In a recent article in the New England Journal of Medicine, Kerlan et al. identify the major cause of failure of prosthetic arteriovenous grafts as stenosis at the venous anastomosis of the graft.1
They indicated that various attempts to prevent or reduce the incidence of this problem through surgical or pharmacologic means have been largely unproductive. The Prolong graft developed by the University of Limerick addresses this issue in a new way.
In 2001, Dr Michael Walsh, then a young PhD student, was completing his studies on vascular haemodynamics when he made an inventive step relating to the creation of a new approach to flow behaviour at the distal junction of a vascular graft. He had concluded that the traditional end-to-side anastomosis (Figure 1) was a flawed configuration.
Fig 1:Illustration of a typical vascular bypass.
With permission from Proceedings of I Mech E, Vol. 217 Part H, J. Engineering in Medicine, HO1092, IMechE 2003
He noted that a typical end-to-side junction had a tendency to induce further disease formation at the junction between the bypass graft and the downstream junction as the blood re-entered the host vessel.2
He proposed and subsequently demonstrated the benefits of an alternative configuration (Figures 2 and 3).
Fig 2:The prolong concept design
He and I and our collaborating vascular surgeon Professor Pierce Grace discussed the concept in detail and based on our deliberations we decided to file for patent protection of the concept. Following extensive discussions with the University's Technology Transfer Office we sought funding support from Enterprise Ireland to advance the technology to the next level. At this point it was decided to defer the filing of a patent application until further development work had been completed.
Fig 3:Computational models showing flow behaviour of the Prolong concept (A) and an experimental test validating the concept (B).
A successful grant application allowed Dr Walsh to continue the research on the concept as a Post Doctoral Fellow and we subsequently filed for a patent in July 2003. "The reconfigured junction in the graft dramatically improved the flow behaviour and the rapid flow recovery downstream of the junction led us to believe that this approach could lead to the development of more effective vascular grafts and thereby improve patient care," stated Dr Walsh.
Spurred on by the quality of our computational modelling we sought additional grant support from Enterprise Ireland in 2003 and this enabled us to expand our horizons beyond the academic environment. We now had sufficient funds to investigate the creation of prototypes and identify the market leaders in the vascular graft sector.
Among the companies we identified were CR Bard, WL Gore, Boston Scientific and B Braun. Of these, only Boston Scientific (www.bostonscientific.com
) had an Irish facility. This facility was involved in cardiology and not vascular grafts and the Irish management provided introductions to the relevant vascular technology personnel at the company's US facilities. We quickly learned that manufacture of vascular grafts was a challenging process and particularly so in the case of manufacture of our novel Prolong vascular graft (Figure 4).
Fig 4: The Prolong vacsular graft (polyester model)
The graft was targeted at peripheral vascular disease, namely femoral arteries or femoral popliteal arteries that are normally treated with saphenous vein or conventional polyester (Dacron) vascular grafts. An important element of our second grant was the preparation of a protocol for pre-clinical evaluation of the device. This was a first for the University.
We engaged in detailed discussions with a variety of centres that had animal facilities in Ireland and overseas. Initially, a simple animal study was conducted to prove surgical feasibility at the Royal College of Surgeons in Ireland (www.rcsi.ie
). Then, based on comments from the operating surgeon, a preclinical study in the carotid artery of six sheep was conducted at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, USA, (www.mirm.pitt.edu
) under the direction of Professor Stephen Badylak. This decision was based on cost and the need to conduct the study at a well known facility. The study was highly successful with six Prolong grafts remaining open, four of them for a full six months.
These positive findings enabled us to obtain additional funding support from Enterprise Ireland for more commercialisation work and patent protection. We took a stand at the 28th Charing Cross International Symposium, held at Imperial College London in April 2006 where we presented our results. There was considerable interest and this spurred us to attend the annual European Vascular Surgery meeting in Prague the same year where we had positive discussions with a number of parties.
Artero-venous access application
Major changes were taking place in the vascular graft business. Large companies such as Boston Scientific and Edwards Lifesciences were exiting the sector and new treatment options such as balloon angioplasty and peripheral stenting were being introduced as clinical alternatives to the invasive approach offered by the Prolong device.
We established that the device could be introduced into the United States (US) market on a 510k regulatory path. We proceeded to win further funding support from Enterprise Ireland to investigate the use of the Prolong device in in artero-venous (AV) vascular access procedures for treatment of renal disease. This further grant support was contingent on us identifying a large market with an unmet clinical need.
We were aware that vascular grafts were widely used in AV vascular access procedures for treatment of renal disease and that the clinical performance of these end-to-side grafts was generally poor. Of particular importance for this application was the use of expanded polytetrafluoroethylene (ePTFE) as the material of choice for the graft due to its better needle "stickability." It is important that the material used ensures rapid sealing following needle insertion.The major players in the sector in which the US is the largest market are CR Bard and WL Gore; both companies had viewed the earlier Dacron version of the Prolong graft.
The additional funding was required to assess manufacturability of the Prolong shape in ePTFE for the AV access application and an additional preclinical study in a porcine model. The choice of the porcine model was based on industry recommendations and on previously published work on ePTFE devices.3
During this time the patent process had progressed to nationalisation and examiner review in the US and Europe. We decided to conduct two additional preclinical studies, one at the McGowan Institute and the second at the Duke University Medical Centre (http://medschool.duke.edu
) under the guidance of Professor Jeffrey Lawson, a leading authority on vascular access, who had extensive experience in preclinical and clinical investigations of these devices.
Manufacture of the device proved challenging and required considerable development effort by Atrium Medical (www.atriummed.com
), which produced devices of sufficient quality for the preclinical investigation (Figure 5).
Fig 5: Prolong AV vascular access configuration (ePTFE)
Additional market information was obtained by attending the 35th Annual Veith Symposium held in New York in November 2008 and at the 32nd International Charing Cross Symposium held at Imperial College, London, in April 2010. At these meetings, the poor clinical outcomes for patients, who were treated using an AV fistula or using an AV access graft were once more highlighted by numerous speakers.
A series of additional preclinical surgeries were all completed during 2009 and early 2010. The results confirmed once more that the Prolong device provided enhanced protection against intimal hyperplasia compared with conventional end-to-side vascular grafts in the porcine model.
Figure 6 shows that even with no exclusions Prolong has a 41% patency compared with 25% for the conventional graft. When exclusions are included there is a dramatic improvement using the Prolong graft, namely 64% patency versus 25%. Thus we believe that we have developed a unique solution to vascular restenosis in vascular access and peripheral vascular treatments. The Prolong graft has the following unique features, it
Figure 6: Results from Prolong AV access study compared with published data
uses optimised haemodynamics to prevent blockage at the venous anastomosis of the graft
- has been shown to outperform current grafts in three animal investigations
- has recently been granted full patent protection in the US and Europe.
from Baig et al. (2003)
The University of Limerick's Technology Transfer Office would welcome enquiries from interested parties, who would be capable of taking this technology to first-in-human studies and full commercialisation. Contact Dr Seamus Browne, e-mail: email@example.com
The authors would like to acknowledge support from the following people: Professor Pierce Grace (Consultant Vascular Surgeon, Limerick), Mr Eamon Kavanagh (Consultant Vascular Surgeon, Limerick), Dr Liz Moran (Senior Biotechnology Analyst, Enterprise Ireland) and Dr Seamus Browne (Technology Transfer Office, University of Limerick). The research described in this paper has been supported by Enterprise Ireland Research Innovation Fund (R IF/2001/0057) and the Commercialisation Fund (CFTD/03/113, CFTD 05/BRI/121 and CFTD/07/101) with support from EU Structural Funds and the Irish National Development Plan.
1. R.K. Kerlan Jr and J.M. LaBerge, ‚€úFistula First, Stent Graft Second, "N. Engl. J. Med., 362, 550-552 (2010).
2. M.T. Walsh et al., "On the Existence of an Optimum End-to-Side Junctional Geometry in Peripheral Bypass Surgery - A Computer Generated Study, "Eur. J. of Vasc. and Endovasc. Surg., 26, 6, 649-656 (2003).
3. K. Baig et al., "A Porcine Model of Intimal-Medial Hyperplasia in Polytetrafluoroethylene Arteriovenous Grafts, " J. Vasc. Access, 4, 3, 111-117 (2003).
Professor Timothy M.McGloughlin
is Associate Professor, Mechanical, Aeronautical and Biomedical Engineering, and Director of the Centre for Applied Biomedical Engineering Research, University of Limerick, Ireland,
tel. +353 61 202 217,
e-mail: firstname.lastname@example.org , www.ul.ie
Dr Michael Walsh
is Lecturer, Department of Mechanical, Aeronautical and Biomedical Engineering and Manager, Centre for Applied Biomedical Engineering Research, University of Limerick, Ireland,
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