? Current biomaterials suffer from well-known problems including thrombosis, excessive wound healing, and infection. The surface, or interface, of a biomaterial is one of the most important factors that determine these host responses. The proposed studies focus on new biomimetic interface materials designed to improve host responses to biomaterials, and are based on the central hypothesis that controlled spatial placement of oligosaccharides and/or cell adhesion peptides on a biomaterial will facilitate programmed biological responses that minimize non-specific interactions, and enhance selective cell-surface interaction and shear stable surface endothelialization. Proposed research will be focused through two operational paradigms, 'cell surface glycocalyx' and 'extracellular matrix' (ECM), that provide guidance in biomimetic designs and focus specific research on: (1) Biomimetic materials that mimic the non-adhesive properties and anticoagulant function of a glycocalyx, designed to improve blood compatibility; and (2) biomimetic materials that mimic adhesive glycoproteins in the ECM designed to facilitate shear stable endothelialization. The biomimetic materials undergo surface-induced assembly on a range of clinically relevant biomaterials, and consist of surfactant polymers with pendant oligosaccharides, peptides, and hydrophobic ligands. The oligosaccharides include glycodendrimers and bottle-brush constructs that will provide a dense glycocalyx-like interface. ECM-like biomimetic materials incorporate high affinity integrin binding and heparin proteoglycan binding peptides, characterized by spectroscopic and microscopic techniques including methods to assist in the quantification of surface ligand densities and nanoscale imaging of surface assemblies. In vitro blood compatibility will be determined from spectroscopic, microscopic, and labeling measurements under well defined flow conditions. Endothelial cell studies will include shear-dependent analysis of actin stress fibers and focal adhesion proteins using confocal microscopy. Blood compatibility also will be determined using a well-established porcine a-v shunt model. From these studies, we shall determine the mechanisms by which alterations in the biomimetic interface correlates to blood compatibility and shear stable endothelialization. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB002067-17
Application #
7115826
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Lee, Albert
Project Start
1988-03-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
17
Fiscal Year
2006
Total Cost
$336,161
Indirect Cost
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Takaseya, Tohru; Fumoto, Hideyuki; Zhu, Junmin et al. (2018) Acute Swine Model for Assessing Biocompatibility of Biomedical Interface Materials. Tissue Eng Part C Methods 24:69-73
Dudash, Lynn A; Kligman, Faina L; Bastijanic, Jennifer M et al. (2014) Cross-reactivity of cell-selective CRRETAWAC peptide with human and porcine endothelial cells. J Biomed Mater Res A 102:2857-63
Dudash, Lynn A; Kligman, Faina; Sarett, Samantha M et al. (2012) Endothelial cell attachment and shear response on biomimetic polymer-coated vascular grafts. J Biomed Mater Res A 100:2204-10
Zhu, Junmin (2010) Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 31:4639-56
Beamish, Jeffrey A; He, Ping; Kottke-Marchant, Kandice et al. (2010) Molecular regulation of contractile smooth muscle cell phenotype: implications for vascular tissue engineering. Tissue Eng Part B Rev 16:467-91
Beamish, Jeffrey A; Zhu, Junmin; Kottke-Marchant, Kandice et al. (2010) The effects of monoacrylated poly(ethylene glycol) on the properties of poly(ethylene glycol) diacrylate hydrogels used for tissue engineering. J Biomed Mater Res A 92:441-50
Kumar, Aryavarta M S; Fox, Justin D; Buerkle, Lauren E et al. (2009) Effect of monomer structure and solvent on the growth of supramolecular nanoassemblies on a graphite surface. Langmuir 25:653-6
Zhu, Junmin; Tang, Chad; Kottke-Marchant, Kandice et al. (2009) Design and synthesis of biomimetic hydrogel scaffolds with controlled organization of cyclic RGD peptides. Bioconjug Chem 20:333-9
Wang, Shuwu; Gupta, Anirban Sen; Sagnella, Sharon et al. (2009) Biomimetic fluorocarbon surfactant polymers reduce platelet adhesion on PTFE/ePTFE surfaces. J Biomater Sci Polym Ed 20:619-35
Tang, Chad; Kligman, Faina; Larsen, Coby C et al. (2009) Platelet and endothelial adhesion on fluorosurfactant polymers designed for vascular graft modification. J Biomed Mater Res A 88:348-58

Showing the most recent 10 out of 22 publications