Functional Analysis of Bone-Biomaterial Interface

Proper function and long-term stability of orthopaedic implants depend on the intimate association between bone cells and the implant biomaterial, a process known as osseointegration. Understanding the processes responsible for the establishment and maintenance of a functional bone-biomaterial interface and how these processes may be enhanced is crucial to the rational design and optimization of prosthetic devices. We have utilized cellular, molecular, and high-resolution imaging approaches to analyze the mechanistic basis of bone-biomaterial interactions. Specifically, we have characterized the initial adhesion of osteoblasts in terms of kinetics and relationship to the surface topography and chemistry of the biomaterials, particularly the cobalt-chrome and titanium alloys commonly used to fabricate orthopaedic prostheses. Results from these studies indicate that the long-term performance of osteoblasts adherent to biomaterials is crucially dependent on the characteristics of the initial adhesion step. Furthermore, osteoactive factors such as members of the transforming growth factor-β superfamily, including TGF-β1 and BMP-2, significantly enhance osteoblast cell adhesion. The molecular components responsible for the adhesion process include extracellular matrix proteins (e.g. fibronectin and collagen type I) and their cognate membrane receptors, the integrins. Our recent studies reveal that specific downstream, intracellular signaling events are also activated as a result of osteoblast adhesion, and that these signaling events are coupled to signal transduction mechanisms mediating growth factor activity. These events in combination regulate the continued expression and maintenance of the osteoblastic phenotype of the adherent cells, resulting in matrix maturation and mineralization, hallmarks of the bony tissue. Our current efforts focus on defining the target molecular pathways responsible for bone cell functioning on biomaterials, and the identification of critical biological and material parameters to optimize long-term osteoblast function and interaction with orthopaedically relevant biomaterials. The information gathered from these studies should provide a rational basis for the design of optimal implant biomaterials. (Supported in part by the NIH and the Annenberg Foundation)