Item Details

title

Mechanistic Investigation of A Hemostatic Keratin Biomaterial

author

Rahmany, Maria Bahawdory

abstract

Traumatic injury leads to more productive years lost than heart disease, cancer and stroke combined. Trauma is often accompanied and complicated by uncontrolled bleeding. Human hair keratin biomaterials have demonstrated efficacy in controlling hemorrhage in both small and large animal models; however little is known about the mechanism by which these proteins aid in blood clotting. Inspection of the amino acid sequence of known keratins shows the presence of several cellular binding motifs, suggesting a possible mechanism and potentially eliminating the need to functionalize the material's surface for cellular interaction. In addition to small animal studies, the hemostatic activity of keratin hydrogels was explored through porcine hemorrhage models representing both a high flow and low flow bleed. In both studies, keratin hydrogels appeared to lead to a significant reduction in blood loss. The promising results from these in vivo studies provided the motivation for this project. The objective of this dissertation work was to assess the mechanism of action of a hemostatic keratin biomaterial, and more broadly assess the biomaterial-cellular interaction(s). It is our hypothesis that keratin biomaterials have the capacity to specifically interact with cells and lead to propagation of intracellular signaling pathway, specifically contributing to hemostasis. Through application of biochemical and molecular tools, we demonstrate here that keratin biomaterials contribute to hemostasis through two probable mechanisms; integrin mediated platelet adhesion and increased fibrin polymerization.

subject

Biomaterial

Blood Clotting

Hemostasis

Integrin

Keratin

Trauma

contributor

Van Dyke, Mark (committee chair)

Saul, Justin (committee member)

Hantgan, Roy (committee member)

Kim-Shapiro, Daniel (committee member)

Hoth, Jason (committee member)

date

2013-06-06T21:19:34Z (accessioned)

2013-06-06T21:19:34Z (available)

2013 (issued)

degree

Molecular Medicine and Translational Science (discipline)

identifier

http://hdl.handle.net/10339/38556 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation