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 responses from surrounding cells/tissues; for example, such biomaterials should support and enhance osteoblast adhesion (a crucial function for anchorage-dependent cells). In the past, integrin-binding peptides have been immobilized on substrates to partially control osteoblast adhesion; the present study focused on the design, synthesis, and bioactivity of the novel peptide sequence Lys-Arg-Ser-Arg that selectively enhances heparan sulfate-mediated osteoblast adhesion mechanisms. Osteoblast, but not endothelial cell or fibroblast, adhesion was enhanced significantly (p < 0.05) on substrates modified with Lys-Arg-Ser-Arg peptides, indicating that these peptides may be osteoblast- or bone cell specific. Blocking osteoblast cell-membrane receptors with various concentrations of soluble Arg-Gly-Asp-Ser peptides did not inhibit subsequent cell adhesion on substrates modified with Lys-Arg-Ser-Arg peptides, providing evidence that osteoblasts interact with Arg-Gly-Asp-Ser and with Lys-Arg-Ser-Arg peptides via distinct (i.e., integrin- and proteoglycan-mediated) mechanisms, each uniquely necessary for osteoblast adhesion. The present study constitutes an example of rational design/selection of bioactive peptides, confirms that osteoblast adhesion to substrates can be controlled selectively and significantly by immobilized peptides, and elucidates criteria and strategies for the design of proactive dental/orthopedic implant biomaterials.
Dee
K C
KC
Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
Andersen
T T
TT
Bizios
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R
D000268:Adhesiveness; D000818:Animals; D001672:Biocompatible Materials; D002460:Cell Line; D017267:Dental Prosthesis Design; D008954:Models, Biological; D010006:Osteoblasts / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D051381:Rats
D001672:Biocompatible Materials; D010455:Peptides