The development of novel synthetic materials based upon biomimetic principles may be an important step in the generation of a biologically functional small diameter arterial prosthesis. The investigators believe that a composite structure with both membrane- and glycosaminoglycan (GAG)-mimetic components provides a rational design strategy for such an approach. Specifically, they intend to: (1) Synthesize and characterize a membrane-mimetic glycocalyx for controlled endothelial regeneration in a thromboresistant microenvironment. Integrin and GAG binding peptide sequences, as well as FGF-2 activating oligosaccharides, derived from heparan sulfate (HS), will be used as pendant groups on polymerizable phospholipid macromolecules. Substrate supported membrane assemblies will be produced, polymerized in situ, and both physiochemical and biological properties defined in vitro. (2) Define the structural and physiochemical features of a heparan sulfate based glycopolymer as a tissue regenerating matrix. Heparan-sulfate mimicking glycopolymers will be synthesized utilizing vinyl functionalized oligosaccharide monomers. FGF-2 binding and receptor activating properties will be investigated using both cellular and cell free systems. Glycopolymer/gelatin networks will be formulated with both biologically stable and proteolytically sensitive crosslinks. The ability of these matrix formulations, with or without added FGF-2, to modulate the adhesive, proliferative, and migratory properties of endothelial and smooth muscle cells will be defined. (3) Characterize the biomimetic material properties which influence thromboresistance and spontaneous endothelialization in vivo. A small diameter vascular prosthesis will be functionalized with using a baboon ex vivo shunt model and primate implant studies performed to characterize endothelial regeneration and graft patency.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-F (M1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
Schools of Medicine
United States
Zip Code
Dydek, E Victoria; Chaikof, Elliot L (2016) Simulated thrombin responses in venous valves. J Vasc Surg Venous Lymphat Disord 4:329-35
Dydek, E Victoria; Chaikof, Elliot L (2016) Simulated Thrombin Generation in the Presence of Surface-Bound Heparin and Circulating Tissue Factor. Ann Biomed Eng 44:1072-84
Ayala, Perla; Caves, Jeffrey; Dai, Erbin et al. (2015) Engineered composite fascia for stem cell therapy in tissue repair applications. Acta Biomater 26:1-12
Kumar, Vivek A; Martinez, Adam W; Caves, Jeffrey M et al. (2014) Microablation of collagen-based substrates for soft tissue engineering. Biomed Mater 9:011002
Kumar, Vivek A; Caves, Jeffrey M; Haller, Carolyn A et al. (2013) Acellular vascular grafts generated from collagen and elastin analogs. Acta Biomater 9:8067-74
Kim, Wookhyun; Xiao, Jiantao; Chaikof, Elliot L (2011) Recombinant amphiphilic protein micelles for drug delivery. Langmuir 27:14329-34
Caves, Jeffrey M; Cui, Wanxing; Wen, Jing et al. (2011) Elastin-like protein matrix reinforced with collagen microfibers for soft tissue repair. Biomaterials 32:5371-9
Dong, He; Song, Xuezheng; Lasanajak, Yi et al. (2010) Facile construction of fluorescent peptide microarrays: One-step fluorescent derivatization of sub-microscale peptide aldehydes for selective terminal immobilization. Anal Biochem 398:132-4
Sallach, Rory E; Cui, Wanxing; Balderrama, Fanor et al. (2010) Long-term biostability of self-assembling protein polymers in the absence of covalent crosslinking. Biomaterials 31:779-91
Kim, Wookhyun; Chaikof, Elliot L (2010) Recombinant elastin-mimetic biomaterials: Emerging applications in medicine. Adv Drug Deliv Rev 62:1468-78

Showing the most recent 10 out of 23 publications