The development of a completely tissue-engineered small-caliber prosthesis suitable for incorporation into an in vivo vascular network is fraught with many challenges, including overcoming resistance to endothelialization and susceptibility to thrombogenesis. In this work, recombinant human fibronectin-derived low-molecular-weight peptide fragments were studied for their ability to promote cell type-specific α4 integrin-mediated adhesion. Two populations of primary human endothelial cells were examined and found to express α4 integrin receptors on their surfaces; on the contrary, human platelets were not found to be expressers of α4 integrins. A peptide fragment isolated from the variably spliced human fibronectin type III connecting segment-1 (CS-1) domain was determined to mediate statistically significant endothelial cell α4 integrin-mediated adhesion. In contrast, the fibronectin type III CS-1 fragment did not support human platelet adhesion under physiological fluid shear conditions, although fully intact human fibronectin molecules supported shear-induced platelet adhesion. This suggests that platelets bind to fibronectin in regions not encompassing the CS-1 domain. In conclusion, this work has demonstrated that the low-molecular-weight peptide CS-1 could serve as a cell-selective adhesion mediator in the engineering of a more-compatible small-caliber vascular graft lumen interface.
ASJC Scopus subject areas
- Cell Biology