Engineered PlyCB as a Novel Implant Coating for Osseointegration.

摘要

Orthopedic implant materials are often not compatible with osteoblasts, bone cells responsible for formation of new bone. The lack of osseointegration is the primary cause of implant failure or shortened lifespan under physiological loads. Coatings such as hydroxyapatite, the mineral component of bone, are often used to promote integration of bone with implant. However, hydroxyapatite coatings do not contain any inherent bioactive properties. Integrins are a family of bioactive proteins that promote adherence of osteoblasts to extracellular matrix proteins. Significantly, the tri-peptide sequence Arg-Gly-Asp, or RGD , is sufficient to direct binding to several of the predominant integrins including 3, which is displayed by osteoblasts (Morra, 2006). Engineering orthopedic surfaces to display proteins or short peptides such as RGD is an ongoing challenge to the biomaterial field (Carson, 2007; Tsiridis, 2007; Axelrad, 2007; Schuler, 2006). Interestingly, PlyCB, a bacteriophage-derived protein, was found to have a particularly high affinity for hydroxyapatite (Nelson, 2006). Based on the crystal structure, we plan to introduce mutants to PlyCB that will display the RGD motif and hopefully retain the natural ability of this protein to bind hydroxyapatite. The biochemical and biophysical properties of PlyCB when bound to hydroxyapatite will be investigated by several methods. Finally, a sandwich of titanium implant, hydroxyapaptite coating, and PlyCB-RGD mutants will be made and binding to cultured osteoblasts will be determined by fluorescent binding assays. Future proposals will be aimed at in vivo implant models to show increased osteoblast formation on PlyCB-RGD treated implants. Additionally, we envision the ability to display other bonestimulating factors on the surface of PlyCB in future proposals.