Over the past decade considerable advances have been made in the fields of cell and molecular biology; however, little of this technology has been incorporated into the materials or devices used in the fields of physical medicine & rehabilitation or orthopaedic surgery. A long-term goal of this program is to exploit knowledge from these fields to develop biological modifications to materials to improve function and performance of disabled individuals. The term biological modification (or biomimetics) implies altering a material's biocompatibility by covalently coupling to the material's surface a biologically relevant molecule that the tissue surrounding the material recognizes through a cellular or biomolecular pathway. The innovative aspect of this study is the selective covalent immobilization of biologically active molecules that can be performed prior to surgery. This technology has never been applied to materials used in physical medicine & rehabilitation or orthopaedic surgery, and has the potential to revolutionize the way implants are currently designed, i.e. biologically engineered implants. Specifically, this application will address biological modifications to modulate the bonding of bone tissue to prosthetic materials. A major drawback to the implant operation is the recuperation period needed before the patient is able to load the implant. A significant reduction in the time needed for adequate interfacial bonding between the implant and bone could reduce prolonged hospitalization associated with the procedure, decrease costly disability before function is restored, decrease morbidity, increase function, and ultimately lead to making. therapies more widely available. In an effort to reduce this period, this research program proposes to alter the kinetics of bone tissue response to the material by modifying the material's surface with peptides containing signals found in the non-collagenous extracellular matrix protein, bone sialoprotein (BSP), which is localized near osteoblasts in vivo. BSP contains signals for osteoblasts thought to be important for attachment to the extracellular matrix. By utilizing peptides incorporating the osteoblast attachment domain on BSP, one could conceivably promote adhesion of osteoblasts to the implant during the healing stage, which may improve the stability and kinetics of formation of the bone-material interface. The major goal of this application is to test the hypothesis that monolayer (i.e., one molecular layer) coatings of biologically active molecules affects the interfacial bond strength between bulk implants and cortical bone. To reach this goal the following specific aims must be met: covalently graft peptides containing the proposed osteogenic cell-binding signals of BSP to an implant material (e.g., titanium), characterize the surface chemistries of the modifications; develop a rapid in vitro assay predictive of the adhesive properties of biomimetic materials; to use this assay to monitor cell-substratum interactions as a function of biological modification, substrate chemistry, environment and time; and conduct a pilot experiment measuring bone-biomimetic material interfacial bond strength in vivo.
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