Osteoblast response to titanium surfaces functionalized with extracellular matrix peptide biomimetics.
OBJECTIVE
Functionalizing surfaces with specific peptides may aid osteointegration of orthopedic implants by favoring attachment of osteoprogenitor cells and promoting osteoblastic differentiation. This study addressed the hypothesis that implant surfaces functionalized with peptides targeting multiple ligands will enhance osteoblast attachment and/or differentiation. To test this hypothesis, we used titanium (Ti) surfaces coated with poly-l-lysine-grafted polyethylene glycol (PLL-g-PEG) and functionalized with two peptides found in extracellular matrix proteins, arginine-glycine-aspartic acid (RGD) and lysine-arginine-serine-arginine (KRSR), which have been shown to increase osteoblast attachment. KSSR, which does not promote osteoblast attachment, was used as a control.


METHODS
Sandblasted acid-etched titanium surfaces were coated with PLL-g-PEG functionalized with varying combinations of RGD and KRSR, as well as KSSR. Effects of these surfaces on osteoblasts were assessed by measuring cell number, alkaline phosphatase-specific activity, and levels of osteocalcin, transforming growth factor beta-1 (TGF-β1), and PGE(2).


RESULTS
RGD increased cell number, but decreased markers for osteoblast differentiation. KRSR alone had no effect on cell number, but decreased levels of TGF-β1 and PGE(2). KRSR and RGD/KRSR coatings inhibited osteoblast differentiation vs. PLL-g-PEG. KSSR decreased cell number and increased osteoblast differentiation, indicated by increased levels of osteocalcin and PGE(2).


CONCLUSIONS
The RGD and KRSR functionalized surfaces supported attachment but did not enhance osteoblast differentiation, whereas KSSR increased differentiation. RGD decreased this effect, suggesting that multifunctional peptide surfaces can be designed that improve peri-implant healing by optimizing attachment and proliferation as well as differentiation of osteoblasts, but peptide combination, dose and presentation are critical variables.
Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA.
B F
BF
Bell
M
M
Schuler
S
S
Tosatti
M
M
Textor
Z
Z
Schwartz
B D
BD
Boyan
D000134:Acid Etching, Dental / Q000379:methods; D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D001120:Arginine / Q000494:pharmacology; D040761:Biomimetic Materials / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D045662:Dental Etching / Q000379:methods; D003764:Dental Materials / Q000737:chemistry*; D015232:Dinoprostone / Q000032:analysis; D004337:Drug Carriers; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D008422:Materials Testing; D009842:Oligopeptides / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000032:analysis / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry; D012694:Serine / Q000494:pharmacology; D014025:Titanium / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000187:drug effects
D020099:Coated Materials, Biocompatible; D003764:Dental Materials; D004337:Drug Carriers; D016326:Extracellular Matrix Proteins; D009842:Oligopeptides; D053773:Transforming Growth Factor beta1; C437191:lysyl-arginyl-seryl-arginine; C443714:polylysine-graft-(poly(ethylene glycol)); D015675:Osteocalcin; D011107:Polylysine; D011092:Polyethylene Glycols; D012694:Serine; C047981:arginyl-glycyl-aspartic acid; D001120:Arginine; D014025:Titanium; D000469:Alkaline Phosphatase; D008239:Lysine; D015232:Dinoprostone
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