Elucidation of Receptor-ligand Interactions Necessary to Support Endothelialization of Biomaterials Under Shear

Project: Research

Investigators

  • Elizabeth Ann Lipke (PI)

Description

The long-term goal of this research project is to establish a fundamental understanding of the receptor-ligand interactions necessary to support endothelialization of intravascular biomaterials by endothelial progenitor cells (EPCs). Using an innovative, non-traditional additive approach to identify these interactions, the proposed research explores the ability of novel peptide ligands coupled to a poly(ethylene glycol) (PEG) hydrogel system to support EPC rolling, firm adhesion (capture), and migration under physiological shear stress. The specific aims are as follows: (1) Determine the relative capability of peptides which preferentially bind specific integrins, such as alphavbeta3 and alpha5beta1, to enable EPC rolling and capture when coupled to PEG hydrogels; (2) Establish whether combinations of multiple PEG-coupled peptides, each shown previously to support EPC rolling, have an additive capacity to reduce EPC rolling velocity; (3) Explore the ability of PEG-peptide materials to support adherent EPC migration and proliferation under static and physiological shear conditions. EPC rolling has been previously examined on extracellular matrix proteins and interactions with the alphavbeta3 and alpha5beta1integrins have been shown to be involved. However, this traditional experimental system requires that a subtractive approach be taken to identify each type of receptor-ligand interaction, making it very difficult to isolate every individual contributing binding event. Since PEG hydrogels resist protein adsorption, interactions of the EPCs with peptide-coupled PEG hydrogels are dominated by receptor binding to the coupled peptides. Thus, the proposed peptide-coupled PEG hydrogel system can be used to test not only whether specific receptor-ligand interactions are necessary, but also whether these interactions are sufficient to support EPC rolling and firm adhesion. This knowledge is essential to recapitulate this natural process for endothelium repair on the surface of biomaterials. EPCs, specifically endothelial colony forming cells, can be isolated from blood, expanded in vitro, and differentiated into mature endothelial cells, making them a promising autologous cell source. Therefore, creating biomaterials that support EPC rolling, firm adhesion, and migration would greatly advance efforts to endothelialize small diameter vascular grafts in situ, vascularize tissue engineered constructs, and repair areas of the vascular endothelium damaged
Award amount$308,000.00
Award date01/01/2014
Program typeScientist Development Grant
Award ID14SDG18610002
Effective start/end date01/01/201412/31/2017
StatusFinished