No adequate small diameter vascular prostheses are now commercially available, with the major reasons for loss of patency being thrombus formation and neointimal fibrous hyperplasia. This project is designed to improve prosthesis function by covalently immobilizing cell adhesion proteins onto the prosthesis lumen. The proteins are expected to improve initial endothelial cell attachment (EC) attachment, subsequent EC growth, and ultimately promote the establishment of a stable and non-hyperplastic neointima. Phase I results showed that proprietary BSI photoimmobilization technology covalently immobilized active fibronectin and type IV collagen onto four vascular prosthesis materials, with the coated materials showing greatly improved attachment and growth of EC's. Phase II proposes to : 1) optimize protein coatings (as evaluated by promotion of EC cell attachment and growth in vitro) and then 2) evaluate coated prostheses in vivo for improved patency when implanted intrafemorally in dogs. The dog implants will be conducted with and without autologous seeded endothelial cells. Also, antithrombic agents (heparin and hirudin) will be immobilized along with the cell adhesion proteins and evaluated for effectiveness at inhibiting thrombus formation and improving the in vivo development of a stable endothelial layer. small diameter prostheses with greatly improved patency rates would be used for both coronary and peripheral artery reconstructions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44HL040280-03
Application #
3508646
Study Section
Special Emphasis Panel (SSS (B1))
Project Start
1990-09-30
Project End
1994-01-31
Budget Start
1991-09-30
Budget End
1994-01-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Surmodics, Inc.
Department
Type
DUNS #
City
Eden Prairie
State
MN
Country
United States
Zip Code
55344
Dunkirk, S G; Gregg, S L; Duran, L W et al. (1991) Photochemical coatings for the prevention of bacterial colonization. J Biomater Appl 6:131-56