Influence of Surface Composition and Wettability upon Contact Activation of Blood Plasma
Open Access
- Author:
- Bauer, James William
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- May 24, 2011
- Committee Members:
- Christopher Alan Siedlecki, Dissertation Advisor/Co-Advisor
Christopher Alan Siedlecki, Committee Chair/Co-Chair
Erwin A Vogler, Committee Chair/Co-Chair
William Joseph Weiss, Committee Member
Ira Joseph Ropson, Committee Member
Alan J Snyder, Committee Member - Keywords:
- blood plasma coagulation
contact activation
factor XII
self assembled monolayers - Abstract:
- Coagulation resulting from contact activation due to blood-material interactions remains a challenge in the use of blood-contacting medical devices. Our group is investigating the protein-surface interactions influencing material-induced blood plasma coagulation with the goal of contributing towards the rational development of biomaterials with improved hemocompatability. Traditional biochemical theory of contact activation imparts specific activating abilities to negatively-charged hydrophilic surface. However, recent studies have indicated a need to revise this view as activation of blood factor XII (FXII), a contact activation protein, is not specific to negatively-charged surfaces. The central hypothesis of this dissertation proposes that all material surfaces are potential activators of the intrinsic coagulation cascade, but protein adsorption moderates the molecular interactions of contact activation. Measurements of FXII activation in buffer solutions in the presence of mixed thiol self-assembled monolayers suggest a minimum of FXII activation for surfaces with wettabilities nearing 45 dyne/cm. From direct measurement of kallikrein activation at test surfaces we observed that contact activation reactions involving FXII, high-molecular weight kininogen, and prekallikrein are not specific to negatively-charged hydrophilic surfaces, lending further support for the role of protein adsorption-competition at procoagulant surfaces. Preliminary investigations into contact activation of blood plasma coagulation patterned thiol-modified surfaces suggest spatial chemical heterogeneity influences blood plasma coagulation. In summary, the studies described in this dissertation underscore the need to view all materials as potential activators of the intrinsic coagulation cascade with protein adsorption moderating interactions of contact activation proteins.