Adhesion Ligands

Many materials have been modified to contain covalently immobilized adhesive peptide sequences, as summarized in Table III [reviewed in Harbers et al. (2002) and West and Hubbell (1997)]. Interaction of cells with peptide-modified surfaces can occur directly, without mediation by adsorbed proteins. Issues that affect selectivity in cellular attachment to peptide-modified surfaces include spacer length, peptide surface 

Examples of Several Adhesive Peptides that have been Immobilized to a Variety of Substrate Materials 

Utilization of cell-specific peptide sequences in biomaterials enables the selective adhesion of certain cell types, even in the presence of a mixture of many cell types. As mentioned earlier, REDV promotes the adhesion of endothelial cells, but not other vascular cell types (Hubbell et al., 1991). This selectivity has great potential for endothelialization of vascular devices, where the growth of an endothelial cells, but not fibroblasts or smooth muscle cells, is desired. Another peptide sequence, KRSR, has been shown to selectively promote the adhesion of osteoblasts, which is useful in the rational design of better dental and orthopedic biomaterials (Dee et al., 1998). 

Hepatocytes are a cell-type, of particular interest in tissue engineering due to the regenerative capacity of the liver and the quantity of waiting liver transplant recipients, for which there are too few available organ donors. While the asialoglycoprotein receptor on hepatocytes does not 

Exploitation of our knowledge of cell-material interactions can allow the bioengineer to rationally design appropriate materials for applications such as tissue engineering. 

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Good transport of nutrient to cells and products from cells Can be easily modified with cell adhesion ligands Can be injected in vivo as a liquid that gets at body temperature Usually biocompatible Disadvantages Can be hard to handle... 

After a masterful introduction of the field and its new directions by Michael Sefton of the University of Toronto, Kristi Anseth of the University of Colorado offers a critical analysis of cell-materials interaction problems with emphasis on the nature of cell adhesions, adhesion ligands, and surface chemistry. 

Carlos T, Kovach N, Schwartz B, et al. Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells Endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1. Blood 1991 77 2266-2271. 

Drumheller SD, Hubbell JA (1995) Surface immobilization of adhesion ligands for investigations of cell substrate interactions. In Bronzino JD (ed) The biomedical engineering handbook. CRC Press, Boca Raton, FI, p 1584... 

Diamond, M. S., Garcia-Aguilar, J., Bickford, J. K., Corbi, A. L., and Springer, T. A. (1993). The I domain is a major recognition site on the leukocyte integrin Mac-1 (CDllb/CD18) for four distinct adhesion ligands. J. Cell. Biol. 120, 1031-1043. 

Fig. 4 Reaction of EDC/sulfo-NHS activated heparin with amine-end-functionahsed star-PEG to form biohybrid gels. Gel materials are additionally modified with adhesion ligands (integrin binding RGD peptides) and loaded with soluble signalling molecules (growth factors, e.g. FGF-2). The covalent cross-links (dashed lines) could he replaced by use of enzymatically cleavable crosslinks (e.g. matrix metalloprotease sensitive peptide sequences) to allow for remodelling of the matrix by invading cells...

Fig. 5). Furthermore, RGD peptides were covalently attached to EDC/sulfo-NHS activated carboxylic acid functionalities of heparin. A wide variety of growth factors (such as FGF-2) can be incorporated through noncovalent interactions with heparin (Freudenberg et al. 2009). Biofunctionalisation was found to correlate well with the heparin content of the structurally different materials (type A to C, Figs. 5 and 7), as shown for the attachment of adhesive ligands. This allows for an independent variation of mechanical properties at constant biomolecular characteristics. 

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