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 tis sues. After implantation the implant surface is often separated from the su rrounding healthy and regenerating tissues, for example by a fibrous capsul e. To avoid this host-versus-graft reaction, a strong mechanical contact be tween tissue and implant must be ensured. An enhance contact between graft and the surrounding tissue can be provided by coating the implant with cell -adhesive molecules. The highly active and alpha (nu)beta (3)- and alpha (n u)beta (5)- integrin-selective peptide c(-RGDfk-) (f = D- phenylalanine) wa s functionalized with various linker molecules containing an acrylamide end group by using the lysine side chain of c(-RGDfk-). The acrylamide group c an be used to bind the peptide covalently to poly(methyl methacrylate) (PMM A) surfaces. The coated surfaces effectively bind to murine osteoblasts as well as human osteoblasts in vitro when a minimum distance of 3.5 nm betwee n surface and the constrained RGD sequence is provided. In contrast to oste oblasts 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 (nu)-selective peptides affords a ma rked improvement in osteoblast binding over current technologies. In vivo s tudies show that peptide-coated PMMA pellets implanted into the patella gro ove of rabbits are integrated into the regenerating bone tissue faster and more strongly than uncoated pellets.