Cardiac valve repair or replacement is indicated when progression of degenerative disease or bacterial infection of the native valve results in valvular dysfunction, thereby impacting cardiac output. Both procedures require the use of a woven or knitted polyester material with an internal reinforcement (Teflon, silicone or metal) to either stabilize the native valve (annuloplasty ring) or to attach a prosthetic heart valve (sewing cuff). Bacterial infection (prosthetic valve endocarditis or PVE) is a major complication associated with implantation of these devices. Bacteremia seeded at the site prior to surgery or nosocomial infection acquired during the surgery or post-operatively are the primary routes of inoculation, resulting in significant morbidity and mortality. Since the functional parts of the mechanical valves are composed of metals, they are incapable of providing the environment for bacterial growth. Infection is typically localized to the prosthesis/tissue interface at the sewing cuff leading to cuff and annular abscess formation. Thus, these rings/cuffs have served as logical targets to provide localized antimicrobial delivery. The goal of this proposal is to develop a novel, completely nanofibrous sewing cuff that will provide localized infection-resistance via release of a selected antimicrobial agent over an extended period of time while permitting complete healing of the device. Our hypothesis is that a novel sewing cuff can be synthesized entirely via electrospinning technology that will have superior infection- resistance and overall healing properties throughout the entire cuff as compared to the current clinically-utilized sewing cuff devices. The specific objectives of Phase I proposal are to: 1) optimize methodology for synthesizing a bioactive nanofibrous polyester sewing cuff (BioCuff) 2) characterize the physical properties of BioCuff device, 3) evaluate drug elution and antimicrobial activity from BioCuffs over time under rigorous washing conditions, 4) examine cell adhesion and ingrowth for the BioCuff device and 5) assess in vivo infection-resistance and healing as compared to clinically-utilized annuloplasty ring using a rat intra-cardiac implantation model. Over 90,000 mechanical and bioprosthetic valves are implanted in the United States each year, with over 280,000 valves implanted worldwide. While the emergence of transcatheter heart valve therapy will reduce selection of these devices for certain procedures, overall valve use is still projected to increase due to an aging population and, to a lesser extent, a more aggressive surgical approach to mitral valve insufficiency. Higher incidences of obesity and diabetes are also drastically going to increase their use. To date, the associated health care cost from PVE in the US alone is projected to be $60,000 per patient. Thus, the annual global market for prosthetic heart valves alone is projected to range from $700 million to $1.4 billion by 2016. This technology can also be utilized to replace existing valves that have failed due to PVE as well as potentially applied to other devices such as transcatheter heart valves, catheter cuffs for ventricular assist devices, vascular grafts and carotid patch material. Successful completion of these studies will ready the technology for sheep mitral valve implantation studies in Phase II that will be utilized to acquire interest for future development of this novel technology either through licensing or strategic partnerships to companies such as Biomedical Structures (OEM manufacturer) and Edwards Lifesciences as outlined in the SBIR Declaration section.

Public Health Relevance

Cardiac valve repair or replacement is indicated when progression of degenerative disease or bacterial infection of the native valve results in valvular dysfunction, thereby impacting cardiac output. Both procedures require the use of a woven or knitted polyester material with an internal reinforcement (Teflon, silicone or metal) to either stabilize the native valve (annuloplasty ring) or to attach a prosthetic heart valve (sewing cuff). Bacterial infection (prosthetic valve endocarditis or PVE) is a major complication associated with implantation of these devices. Infection is typically localized to the prosthesis/tissue interface t the sewing cuff leading to cuff and annular abscess formation. The goal of this proposal is to develop a novel, completely nanofibrous sewing cuff that will provide localized infection-resistance via release of a selected antimicrobial agent over an extended period of time while permitting complete healing of the device. Over 90,000 mechanical and bioprosthetic valves are implanted in the United States each year, with over 280,000 valves implanted worldwide. While the emergence of transcatheter heart valve therapy will reduce selection of these devices for certain procedures, overall valve use is still projected to increase due to an aging population and, to a lesser extent, a more aggressive surgical approach to mitral valve insufficiency. Higher incidences of obesity and diabetes are also drastically going to increase their use. To date, the associated health care cost from PVE in the US alone is projected to be $60,000 per patient. Thus, the annual global market for prosthetic heart valves alone is projected to range from $700 million to $1.4 billion by 2016. This technology can also be utilized to replace existing valves that have failed due to PVE as well as potentially applied to other devices such as transcatheter heart valves, catheter cuffs for ventricular assist devices, vascular grafts and carotid patch material.

Agency
National Institute of Health (NIH)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43HL120412-01A1
Application #
8714507
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lee, Albert
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Biosurfaces
Department
Type
DUNS #
City
Ashland
State
MA
Country
United States
Zip Code
01721