Surface coating with cyclic RGD peptides stimulates osteoblast adhesion and proliferation as well as bone formation.
The physiological inertness of synthetic implant materials often results in insufficient implant integration and limited acceptance of implants in tissues. After implantation the implant surface is often separated from the surrounding healthy and regenerating tissue, for example by a fibrous capsule. To avoid this host-versus-graft reaction, a strong mechanical contact between tissue and implant must be ensured. An enhanced contact between graft and the surrounding tissue can be provided by coating the implant with cell-adhesive molecules. The highly active and alpha(v)beta(3)- and alpha(v)beta(5)-integrin-selective peptide c(-RGDfK-) (f=D-phenylalanine) was functionalized with various linker molecules containing an acrylamide end group by using the lysine side chain of c(-RGDfK-). The acrylamide group can be used to bind the peptide covalently to poly(methyl methacrylate) (PMMA) surfaces. The coated surfaces effectively bind to murine osteoblasts as well as human osteoblasts in vitro when a minimum distance of 3.5 nm between surface and the constrained RGD sequence is provided. In contrast to osteoblasts in cell suspension, surface-bound osteoblasts show no apoptosis but proliferate by a factor of 10 over a 22 d period. Coating of inert implant surfaces with highly active and alpha(v)-selective peptides affords a marked improvement in osteoblast binding over current technologies. In vivo studies show that peptide-coated PMMA pellets implanted into the patella groove of rabbits are integrated into the regenerating bone tissue faster and more strongly than uncoated pellets.
Kantlehner
M
M
Institut für Organische Chemie und Biochemie Technische Universität München Lichtenbergstrasse 4, 85747 Garching Germany.
Schaffner
P
P
Finsinger
D
D
Meyer
J
J
Jonczyk
A
A
Diefenbach
B
B
Nies
B
B
Hölzemann
G
G
Goodman
S L
SL
Kessler
H
H
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis; D019904:Polymethyl Methacrylate / Q000378:metabolism*; D011817:Rabbits; D019030:Receptors, Vitronectin / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
D020099:Coated Materials, Biocompatible; D009842:Oligopeptides; D019030:Receptors, Vitronectin; D019096:Vitronectin; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; D019904:Polymethyl Methacrylate