Engineering Titanium for Improved Biological Response (2002)

The human body and its aggressive environment challenge the survival of implanted foreign materials. Formidable biocompatibility issues arise from biological, chemical, electrical, and tribological origins. The body's electrolytic solution provides the first point of contact with any kind of implant, and is responsible for transport, healing, integration, or attack. Therefore, determining how to successfully control the integration of a biomaterial should begin with an analysis of the early interfacial dynamics involved. setting, a complicated feedback system of solution chemistry, pH, ions, and solubility exists. The introduction of a fixation device instantly confounds this system. The body is exposed to a range of voltages, and wear can bring about significant shifts in potentials across an implant. In the environment of a new implant the solution pH becomes acidic, ionic concentrations shift, cathodic currents can lead to corrosion, and oxygen levels can be depleted; all of these impact the ability of the implant to retain its protective oxide layer and to present a stable interface for the formation of a biolayer. Titanium has been used in orthopedic and maxilofacial surgery for many years due to its reputation as being biocompatible and its ability to osseointegrate. Osseointegration is defined as direct structural and functional connection between ordered, living bone, and the surface of a load carrying implant. Branemark discovered this phenomenon in the 60's while examining titanium juxtaposed to bone. The mechanism by which titanium and its passivating oxide encourage osseosynthetic activity remains unknown. However in general terms the oxide film serves two purposes: first to provide a kinetic barrier that prevents titanium from corroding and second to provide a substrate that allows the constituents of bone (calcium phosphate crystals, cells, proteins, and collagen) to bond to it. We believe that the electrochemical environment dictates the titanium dioxide surface atomic structure and the biological response at an implantation site. To date, most researchers in this area have surgically implanted materials into living organisms and then retrieved the implant after varying amounts of time have elapsed. The virtue of this style of experiment is that the full, correct chemistry of the body acts on the implant. The difficulty with these experiments is that it is then impossible to link cause with effect because too many variables are changing simultaneously. Another difficulty is that changes in the very early times are missed. The purpose of these experiments is to visualize the early time response of oxide films to electric fields and to solution variations found in the body near bone. Specifically these studies are meant to understand how chemical and electric stress affect the corrosion resistance and the formation of a biolayer. Instead of performing in vivo experiments as described above, our strategy uses titanium manufactured for implants and places these samples in controlled, simplified, solutions that mimic the electrolytic environment near the bone. We use an electrochemical atomic force microscope to image the real-time dynamics of the substrate in One of the most remarkable systems in the body is bone remodeling. Even in a purely natural solution as the oxide film is growing. While imaging we apply a potential between a reference electrode and the titanium substrate which creates a driving force for oxide growth and dissolution. We simultaneously collect the transient current that flows across the oxide layer and use step impedance polarization spectroscopy to determine electrical properties of the oxide layer. We will look for films that successfully nucleate the calcium phosphate crystals that comprise the inorganic phase of bone, but do not corrode under these challenging conditions. The goal is to correlate corrosion resistance and biolayer adhesion with oxide film morphology and material properties in physiological environments. Research is geared towards answering the following questions: (1) How do the material properties such as structure, donor density, and open circuit potential (OCP) change, as the oxide is grown? (2) How does the surface morphology correlate with the material properties? and (3) How do these changes impact nucleation of calcium phosphate or adhesion of cells?