Current gold standards for hemodialysis access to treat End-Stage Renal Disease (ESRD), radial cephalic vein fistulas and autogenous saphenous veins, have significant problems associated with their use. The issues range from unavailability of a healthy vein the patient can spare complexity of harvesting and longevity of the surgical procedure to the long time (4-6 months) required for healing of the fistula. Synthetic grafts made of ePTFE and polyurethane (PU) have issues of low patency (20% for 2 years), delayed access time to first puncture (more than 3 weeks), infection, weeping (leading to hematomas/seroma formation) and kinking of the native vein resulting in graft thrombosis. Thus, there is a need to develop an off-the shelf prosthetic graft that would give comparable or higher patency to autologous grafts or fistulas, eliminate/reduce infection, prevent surface thrombus formation inhibit uncontrolled cellular proliferation throughout graft and most importantly, provide instant access to puncture. Research objectives proposed and accomplished in Phase I were: 1) synthesis of a novel nanofibrous bioactive hemodialysis graft (BioAccess) via electrospinning of polyester and polyurethane in combination with antithrombin, antimicrobial and anti-proliferative agents, 2) characterization of the physical and chemical properties of the BioAccess graft, 3) determination of the release pharmacokinetics from the BioAccess graft, and 4) evaluation of the biologic properties of the BioAccess grafts after undergoing stringent wash conditions. The goal of the Phase II study is to assess in vivo the BioAccess grafts (6mm ID) as well as clinically utilized ePTFE grafts in a canine arteriovenous (carotid artery to jugular vein) shunt access model. BioAccess grafts will be evaluated for patency, infection-resistance, gross hematoma formation, surface thrombus formation and hyperplasia formation after being punctured various times for 30 and 60 days. Our hypothesis is that the BioAccess Graft will become the new standard for hemodialysis access by outperforming ePTFE grafts in terms of immediate access, reduced hematoma formation, low incidences of infection and increased primary patency rates. The BioAccess graft will be superior to ePTFE grafts due to its better mechanical compliance in conjunction with localized release of antithrombotic, antimicrobial and anti- proliferative agents, thereby regulating any potential complications directly at the graft surface. The specific objectives for Phase II are to: 1) electrospin BioAccess grafts for implantation studies, qualify physical, chemical and surface properties of BioAccess grafts, 3) confirm biologic properties of BioAccess graft using established assays employed in Phase I, 4) implant BioAccess and control ePTFE grafts into a canine arteriovenous shunt access model for 30 and 60 days in conjunction with numerous needle punctures and 5) macroscopically and histologically analyze explanted BioAccess and ePTFE grafts. The overall annual cost of ESRD treatment in the US is $23 billion, which is projected to increase at an annual rate of 3.6%. About 2 million patients worldwide (355,000 in US alone) currently will receive hemodialysis treatment by 2012. Approximately 140,000 access grafts are currently implanted in the US at a total healthcare cost of $80 million. Temporary catheters are the most expensive of all the ESRD treatments for Medicare, costing about $77,000/person/year, a cost that can be avoided by immediate access through a permanent arteriovenous graft. With the increase in aging population of ESRD patients, higher occurrence of diabetes and obesity, the options for a patient are reduced to immediate hemodialysis. Thus, there is an increasing demand for hemodialysis grafts with immediate access and better healing properties.

Public Health Relevance

Current gold standards for hemodialysis access to treat End-Stage Renal Disease (ESRD), radial cephalic vein fistulas and autogenous saphenous veins, have significant problems associated with their use. The issues range from unavailability of a healthy vein the patient can spare complexity of harvesting and longevity of the surgical procedure to the long time (4-6 months) required for healing of the fistula. The goal of the Phase II study is to assess in vivo the BioAccess grafts (6mm ID) as well as clinically utilized ePTFE grafts in a canine arteriovenous (carotid artery to jugular vein) shunt access model. BioAccess grafts will be evaluated for patency, infection-resistance, gross hematoma formation, surface thrombus formation and hyperplasia formation after being punctured various times for 30 and 60 days. With the increase in aging population of ESRD patients, higher occurrence of diabetes and obesity, the options for a patient are reduced to immediate hemodialysis. Thus, there is an increasing demand for hemodialysis grafts with immediate access and better healing properties.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44DK084591-02
Application #
8249722
Study Section
Special Emphasis Panel (ZRG1-SBIB-V (12))
Program Officer
Moxey-Mims, Marva M
Project Start
2009-07-01
Project End
2014-02-28
Budget Start
2012-03-10
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$497,370
Indirect Cost
Name
Biosurfaces
Department
Type
DUNS #
131658739
City
Ashland
State
MA
Country
United States
Zip Code
01721