Dental and orthopaedic implants are currently the solutions of choice for teeth and joint replacements with success rates continually improving, but they still have undesirable failure rates in patients who are compromised by disease or age, and who in many cases are the ones most in need. The success of titanium (Ti) implants depends on their ability to osseointegrate with the surrounding bone and this, in turn, is greatly dependent on the surface characteristics of the device. Advancements in surface analysis and surface modification techniques have improved the biological performance of metallic implants by mimicking the hierarchical structure of bone associated with regular bone remodeling. In this process, damaged bone is resorbed by osteoclasts, which produce resorption lacunae containing high microroughness generated after mineral dissolution under the ruffled border, as well as superimposed nanoscale features created by the collagen fibers left at the surface. Indeed, increasing Ti surface roughness at the micro and sub-microscale level has been shown to increase osteoblast differentiation in vitro, increase bone-to-implant contact in vivo, and accelerate healing times clinically. Recently, the clinical application of surface nanomodification of implants has been evaluated. Still, most clinically-available devices remain smooth at the nanoscale and fundamental questions remain to be elucidated about the effect of nanoroughness on the initial response of osteoblast lineage cells. Another property that could be used to control osteoblast development and the process of osseointegration is the electrical surface charge of implants. The presence of endogenous electrical signals in bone has been implicated in the processes of bone remodeling and repair. The existence of these native signals has prompted the use of external electrical stimulation to enhance bone growth in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports confirming its beneficial effects on bone formation. However, the use of electrical stimulation on Ti implants to enhance osseointegration is less understood, in part because of the lack of in vitro models that truly represent the in vivo environment. In addition, an aspect that has not been thoroughly examined is the electrical implication of implant corrosion and its effect on the surrounding tissue. Implants are exposed to extreme conditions in the body such as high pH during inflammation, and cyclic loads. These circumstances may lead to corrosion events that generate large electrochemical currents and potentials, and may cause abnormal cell and tissue responses that could be partly responsible for complications such as aseptic loosening of implants. Consequently, Ti implants with tailored surface characteristics such as nanotopography and electrical polarization, could promote bone healing and osseointegration to ensure successful outcomes for patients by mimicking the biological environment of bone without the use of systemic drugs. The objective of this thesis is to understand how surface nanostructural and electrical characteristics of Ti and Ti alloy surfaces may affect osteoblast lineage cell response in vitro for normal tissue regeneration and repair. Our central hypothesis is that combined micro/nanostructured surfaces, as well as direct stimulation of Ti surfaces with fixed direct current (DC) potentials, can enhance osteoblast differentiation.

Dental and orthopaedic implants are currently the solutions of choice for teeth and joint replacements with success rates continually improving, but they still have undesirable failure rates in patients who are compromised by disease or age, and who in many cases are the ones most in need. The success of titanium (Ti) implants depends on their ability to osseointegrate with the surrounding bone and this, in turn, is greatly dependent on the surface characteristics of the device. Advancements in surface analysis and surface modification techniques have improved the biological performance of metallic implants by mimicking the hierarchical structure of bone associated with regular bone remodeling. In this process, damaged bone is resorbed by osteoclasts, which produce resorption lacunae containing high microroughness generated after mineral dissolution under the ruffled border, as well as superimposed nanoscale features created by the collagen fibers left at the surface. Indeed, increasing Ti surface roughness at the micro and sub-microscale level has been shown to increase osteoblast differentiation in vitro, increase bone-to-implant contact in vivo, and accelerate healing times clinically. Recently, the clinical application of surface nanomodification of implants has been evaluated. Still, most clinically-available devices remain smooth at the nanoscale and fundamental questions remain to be elucidated about the effect of nanoroughness on the initial response of osteoblast lineage cells. Another property that could be used to control osteoblast development and the process of osseointegration is the electrical surface charge of implants. The presence of endogenous electrical signals in bone has been implicated in the processes of bone remodeling and repair. The existence of these native signals has prompted the use of external electrical stimulation to enhance bone growth in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports confirming its beneficial effects on bone formation. However, the use of electrical stimulation on Ti implants to enhance osseointegration is less understood, in part because of the lack of in vitro models that truly represent the in vivo environment. In addition, an aspect that has not been thoroughly examined is the electrical implication of implant corrosion and its effect on the surrounding tissue. Implants are exposed to extreme conditions in the body such as high pH during inflammation, and cyclic loads. These circumstances may lead to corrosion events that generate large electrochemical currents and potentials, and may cause abnormal cell and tissue responses that could be partly responsible for complications such as aseptic loosening of implants. Consequently, Ti implants with tailored surface characteristics such as nanotopography and electrical polarization, could promote bone healing and osseointegration to ensure successful outcomes for patients by mimicking the biological environment of bone without the use of systemic drugs. The objective of this thesis is to understand how surface nanostructural and electrical characteristics of Ti and Ti alloy surfaces may affect osteoblast lineage cell response in vitro for normal tissue regeneration and repair. Our central hypothesis is that combined micro/nanostructured surfaces, as well as direct stimulation of Ti surfaces with fixed direct current (DC) potentials, can enhance osteoblast differentiation.