Principal Investigator: Michele Marcolongo
Abstract: Debilitating degenerative joint diseases are routinely treated by joint replacements to allow restoration of relatively pain-free motion to the affected joint. Fracture healing and bony fusion (for example, in the treatment of degenerative disease) can be facilitated by the use of synthetic bone grafts or tissue engineered scaffolds. The success of each of these surgical interventions is dependent on the ability of bone tissue to integrate with the surface of the implant biomaterial. In order to achieve osseointegration, the bone forming cell (the osteoblast) must first adhere to the biomaterial surface; the osteoblast/biomaterial interaction must then be conducive to the elaboration of a bone-specific extracellular matrix (ECM) which will undergo mineralization and remodeling to form an integrated bone/biomaterial interface. A handful of synthetic biomaterials, termed bioactive materials, will elicit osseointegration; these are calcium phosphate ceramics (including hydroxyapatite) and bioactive glasses. In contrast, the more commonly used bone implant materials, titanium alloy (Ti6A14V) and cobalt chromium alloy, will not support osteoblast adhesion and direct bone bonding in vivo, instead the resulting interface consists predominantly of fibrous tissue. From many experiments it is clear that material properties affecting osseointegration include surface charge, chemistry, and topography, although the specific parameters that facilitate osseointegration are presently poorly understood. Once the specific surface properties which encourage osteoblast attachment are determined, it would then be possible to engineer the surface of any compatible material to make that material bioactive or bone bonding. We suggest that a dominant mechanism in cellular attachment to a biomaterial surface is electrostatic in nature, with the electrostatic characteristics of the surface encouraging the adsorption of specific ECM proteins (in particular, fibronectin, an important serum protein involved in cell adhesion) to facilitate initial attachment of osteoblasts to the biomaterial surface. While evidence of the importance of electrostatic interactions has been documented, the relative contributions of surface charge, charge distribution, and charge density on cellular attachment and protein adsorption are presently not understood. Previous studies have been limited in this regard as they have not uncoupled the electrostatics from functionality and surface energy due to surface chemistry. In this work, we propose a unique model to elucidate the effect of electrostatics on osteoblast adhesion and protein adsorption. We hypothesize that negatively charged surfaces will promote osteoblast attachment and spreading, while positively charged surfaces will inhibit cellular attachment and we expect that osteoblasts will exhibit differential adhesion on surfaces whose charge distribution and charge density has been patterned at varying subcellular dimensions. Further, we hypothesize that the quantity of fibronectin adsorbed to differently charged surfaces will not differ, but the conformation of the fibronectin on those charged surfaces will.
Funding Period: 1998-09-30 - 2002-08-31
more information: NIH RePORT