In vitro modeling of the bone/implant interface.

BACKGROUND

The purpose of this review is to examine the usefulness of cell culture methods to model the mechanisms of bone formation on the surfaces of candidate implant materials.

METHODS

The central objective is to show that in vitro methods are uniquely valuable in providing an understanding of how new bone is formed on solid surfaces. It should be emphasized, at the outset, that the use of cell culture studies as cytotoxicity assays will not be addressed, nor is it implied that cell cultures can model all the complexities of the in vivo environment. Nevertheless, by comparison with in vivo data, which are by nature retrospective, it is shown that primary differentiating osteogenic cell cultures, derived from bone marrow, illustrate a sequence of extracellular matrix elaboration events that characterize the establishment of the interface between newly formed bone and solid surfaces. These solid surfaces either may be implant materials, or indeed previously formed bone matrix, which has been resorbed during normal bone remodeling events. In each case the first biologically derived matrix at these sites is a morphologically distinct collagen fibre-free extracellular matrix, which, in bone histology has been referred to for > 100 years as a cement line.

RESULTS

The sequence starts with secretion and adsorption to the substratum of organic components, of which the major proteins are osteopontin and bone sialoprotein. Mineralization of this matrix occurs by the seeding of nanocrystalline calcium phosphate, which precedes the appearance of morphologically identifiable collagen fibres. This is clearly contrary to the dogma that collagen is necessary for mineralization of bone, but is in agreement with specific cases of other, particularly dental, calcified connective tissues. Although collagen is synthesized by the differentiating osteogenic cells that elaborate the cement line interface, it is not adsorbed to the underlying solid surface. Following the elaboration of the cement line matrix, collagen fibre assembly occurs and is then mineralized to produce morphologically identifiable bone matrix.

CONCLUSION

Key elements of this sequence of events can be seen at the interface of implants retrieved from in vivo experiments, which indicates that these in vitro methods not only mimic known in vivo phenomena, but also provide a mechanistic understanding of bone elaboration at implant surfaces. However, distinction is drawn between the events of new bone formation at implant surfaces and other bone/implant morphologies, which are unrelated to de novo bone formation at the implant surface. Finally, this new information emerging from bone marrow cell culture studies demands a re-examination of the concepts of bone-bonding and nonbonding implant materials.