DESIGN AND FUNCTION OF NOVEL OSTEOBLAST-ADHESIVE PEPTIDES FOR CHEMICAL MODIFICATION OF BIOMATERIALS

Proactive, ''next generation'' dental/orthopedic biomaterials must be designed rationally to elicit specific, timely, and desirable response s from surrounding cells/tissues; for example, such biomaterials shoul d support and enhance osteoblast adhesion (a crucial function for anch orage-dependent cells). In the past, integrin-binding peptides have be en immobilized on substrates to partially control osteoblast adhesion; the present study focused on the design, synthesis, and bioactivity o f the nos el peptide sequence Lys-Arg-Ser-Arg that selectively enhance s heparan sulfate-mediated osteoblast adhesion mechanisms. Osteoblast, but not endothelial cell or fibroblast, adhesion was enhanced signifi cantly (p < 0.05) on substrates modified with Lys-Arg-Ser-Arg peptides , indicating that these peptides may be osteoblast- or bone cell speci fic. Blocking osteoblast cell-membrane receptors with various concentr ations of soluble Arg-Gly-Asp-Ser peptides did not inhibit subsequent cell adhesion on substrates modified with Lys-Arg-Ser-Arg peptides, pr oviding evidence that osteoblasts interact with Arg-Gly-Asp-Ser and wi th Lys-Arg-Ser-Arg peptides via distinct (i.e., integrin- and proteogl ycan-mediated) mechanisms, each uniquely necessary for osteoblast adhe sion. The present study constitutes an example of rational design/sele ction of bioactive peptides, confirms that osteoblast adhesion to subs trates can be controlled selectively and significantly by immobilized peptides, and elucidates criteria and strategies for the design of pro active dental/orthopedic implant biomaterials. (C) 1998 John Wiley & S ons, Inc.