The aim is to understand how platelet adhesion and activation are affected by surface properties of polymers which have been chosen for their potential in biomedical applications, and to relate these responses to their effects on thrombogenicity. The activation of purified human platelets on polymer surfaces, which have been previously characterized by X-ray photoelectron spectroscopy, contact angle, and other techniques; will be studied by Scanning Electron Microscopy, High Voltage Electron Microscopy, and in the living state, by Video-enhanced Differential Interference Contrast Light Microscopy. Differences in cytoskeletal reorganization during shape-change, time and rate of shape-change, appearance and motility of platelet surface receptors, and granule secretion will be analyzed for each surface. Monoclonal antibodies and specific ligands conjugated to colloidal gold will be employed as probes to follow receptor motility by both light and electron microscopy. Differences in shape-change will then be analyzed using pharmacologic agents to modify activation, receptor expression, and cytoskeletal reorganization. These observations will then be related to polymer physicochemical properties. Additionally, three parameters of platelet function which affect thrombogenesis will be analyzed in vitro for the different polymers. These are; platelet dense granule secretion by photoluminescence ATP assay, immuno-gold bead studies of receptor expression, and the extent of activation inducible by platelet agonists. With an iterative process polymers with other surface properties will then be examined. Ultimately, the determination of polymer surface properties which are important in modulating platelet adherence and activation is desired. An understanding of how platelets respond to polymers having different surface properties can provide a basis for developing polymers with minimal adverse effects when placed in the circulation. Knowledge of the mechanisms by which platelets alter their responses to surfaces, as studied through pharmacologic means, could also lead to improved anticoagulant therapies when artificial materials are placed in the circulation. In addition, the observations of receptor appearance and motility, and granule secretion will lead to a better understanding of the platelets' role in modulating thrombosis and to improved in vitro assays for surface thrombogenicity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037351-02
Application #
3352932
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1987-06-01
Project End
1991-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Earth Sciences/Resources
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Goodman, S L; Tweden, K S; Albrecht, R M (1996) Platelet interaction with pyrolytic carbon heart-valve leaflets. J Biomed Mater Res 32:249-58
Simmons, S R; Albrecht, R M (1996) Self-association of bound fibrinogen on platelet surfaces. J Lab Clin Med 128:39-50
Eppell, S J; Simmons, S R; Albrecht, R M et al. (1995) Cell-surface receptors and proteins on platelet membranes imaged by scanning force microscopy using immunogold contrast enhancement. Biophys J 68:671-80
Goodman, S L; Cooper, S L; Albrecht, R M (1993) Integrin receptors and platelet adhesion to synthetic surfaces. J Biomed Mater Res 27:683-95
Olorundare, O E; Simmons, S R; Albrecht, R M (1993) Evidence for two mechanisms of ligand-receptor movement on surface-activated platelets. Eur J Cell Biol 60:131-45
Olorundare, O E; Simmons, S R; Albrecht, R M (1992) Cytochalasin D and E: effects on fibrinogen receptor movement and cytoskeletal reorganization in fully spread, surface-activated platelets: a correlative light and electron microscopic investigation. Blood 79:99-109
Goodman, S L; Cooper, S L; Albrecht, R M (1991) The effects of substrate-adsorbed albumin on platelet spreading. J Biomater Sci Polym Ed 2:147-59
Albrecht, R M; Prudent, J; Simmons, S R et al. (1989) Observations of colloidal gold labelled platelet microtubules: high voltage electron microscopy and low voltage-high resolution scanning electron microscopy. Scanning Microsc 3:273-7;discussion 277-8
Goodman, S L; Cooper, S L; Albrecht, R M (1989) Polyurethane support films: structure and cellular adhesion. Scanning Microsc Suppl 3:285-94;discussion 294-5

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