Osteointegration of Ti Bone Implants: A Study on How Surface Parameters Control the Foreign Body Response

The integration of titanium (Ti)-based implants with bone is limited, resulting in implant failure. This lack of osteointegration is due to the foreign body response (FBR) that occurs after the implantation of biodevices. The process begins with protein adsorption, which is governed by implant surface properties, e.g., chemistry, charge, wettability, and/or topography. The distribution and composition of the protein layer in turn influence the recruitment, differentiation, and modulation of immune and bone cells. The subsequent events that occur at the bone–material interface will ultimately determine whether the implant is encapsulated or will integrate with bone. Despite the numerous studies evaluating the influence of surface properties in the various stages of the FBR, the factors that affect tissue–material interactions are often studied in isolation or in small correlations due to the technical challenges involved in assessing them in vitro or in vivo. Consequently, the influence of protein conformation on the Ti bone implant surface design remains an unresolved research question. The objective of this review is to comprehensively evaluate the existing literature on the effect of surface parameters of Ti and its alloys in the stages of FBR, with a particular focus on protein adsorption and osteoimmunomodulation. This evaluation aims to systematically describe these effects on bone formation.