Peptides Derived from Fibronectin Type III Connecting Segments Promote Endothelial Cell Adhesion but Not Platelet Adhesion: Implications in Tissue-Engineered Vascular Grafts

• Published in: Tissue engineering 2007-11, Vol.13 (11), p.2653-2666
• Main Authors: Rodenberg, Eric J., Pavalko, Fredrick M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biotechnology; Cell adhesion & migration; Cell Adhesion - drug effects; Cell Culture Techniques - methods; Cell Movement - drug effects; Cells, Cultured; Coronary Vessels - cytology; Culture Media; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - physiology; Endothelium, Vascular - cytology; Fibronectins - chemistry; Humans; Integrin alpha4 - metabolism; Models, Biological; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - pharmacology; Peptides; Platelet Adhesiveness - physiology; Prostheses; Recombinant Proteins - chemistry; Recombinant Proteins - pharmacology; Stress, Mechanical; Tissue engineering; Tissue Engineering - methods; Umbilical Veins - cytology
• ISSN: 1076-3279; 1557-8690
• DOI: 10.1089/ten.2007.0037

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 4 integrin-mediated adhesion. Two populations of primary human endothelial cells were examined and found to express 4 integrin receptors on their surfaces; on the contrary, human platelets were not found to be expressers of 4 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 4 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.