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Author Anderson, Eric Hugo
Title Extracellular matrix biomimicry for the endothelialization of cardiovascular materials
Descript 408 p
Note Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2386
Adviser: Roger E. Marchant
Thesis (Ph.D.)--Case Western Reserve University, 2007
A common reason for cardiovascular device failure is biomaterial surface-induced thrombosis. The body's natural defense against this problem is the glycocalyx of endothelial cells (EC) that line the interior of blood vessels. This interface represents the ideal nonthrombogenic surface. The glycocalyx contains a dense array of hydrated polysaccharides and glycoproteins, which combats nonspecific protein adsorption and controls specific interactions. A layer of endothelium on a cardiovascular implant would be most beneficial; however, EC can't attach and proliferate on the hydrophobic surface. To address this problem, novel surfactant polymers were developed to mimic the extracellular matrix and function as an interface between the material surface and EC. These surfactant polymers consist of functional cell-adhesive hydrophilic peptides and alkyl chains for adsorption onto the hydrophobic material coupled to a poly(vinyl amine) (PVAm) backbone. Surfactant polymers are synthesized and characterized at each step by mass spectrometry, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and high-pressure liquid chromatography. Hydrophobic surfaces are prepared and coated with the surfactant polymers followed by surface characterization using contact angle goniometry and AFM. Finally, EC are seeded onto modified surfaces, and attachment and growth are analyzed
A series of surfactant polymers were synthesized by incorporating varying amounts of arginine-glycine-aspartic acid (RGD) peptide on the PVAm backbone. Dextran oligosaccharides were added to keep the hydrophilic:hydrophobic balance constant. Attachment and growth of EC on surfaces with the most RGD peptides was comparable to the fibronectin positive control. Cell adhesion decreased dramatically with decreasing peptide density. Surfactant polymers containing heparin-binding peptides (HBP, interact with EC heparan sulfate proteoglycans) were also synthesized. Compared to fibronectin, EC on HBP surfaces showed more focal adhesions at 3 hours, but significantly less growth over 48 hours. Surfaces with both HBP and RGD showed better cell growth compared to surfaces with RGD alone. Other peptide ligands were synthesized for increased affinity: a cyclic RGD peptide (mimics native loop conformation in fibronectin) and an RGD peptide tethered to the synergy PHSRN peptide using a PEO chain. In conclusion, cell adhesive surfactant polymers can promote EC attachment and growth and would serve as viable coatings for vascular materials
School code: 0042
Host Item Dissertation Abstracts International 68-04B
Subject Chemistry, Polymer
Engineering, Biomedical
Alt Author Case Western Reserve University
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