Dental and medical materials are generally produced using metal alloys, with specific surface properties, allowing functional adaptation to the biological tissue. In order to induce functionality to the material, metallic titanium (Ti) based implants or their alloys are the leading choices due to characteristics such as high mechanical strength and corrosion resistance associated with spontaneous oxidation, with the formation of an amorphous layer of TiO2. This layer induces physical stability, biocompatibility, and ability to osseointegrate, culminating in a satisfactory clinical outcome and long-term performance. Although there is a high and satisfactory implant success rate, failures and complications still occur due to multiple causes, such as pre- or postoperative infections, low bone density associated with diseases such as osteoporosis, in addition to some systemic diseases such as diabetes mellitus, among others. Possible failures and the incomplete osseointegration process, studies have been expanding the search for changes in the surface of the implants that aim to reduce the time of osseointegration, increase the antimicrobial properties and control the immune response caused by the presence of a foreign body, ensuring, thus, favorable conditions for the success of the implant. The proposed modification is based on the addition of drugs to the implant surface, such as bisphosphonates, which are capable of modulating the bone and immune response of biological tissue. Despite being considered potentially inert, the Ti present in the implants, with or without modifications, can interact with the immune system, being characterized as immunomodulatory. The binding of blood proteins and interstitial fluids and the arrival of immune system cells such as neutrophils, monocytes, and macrophages are the initial processes involving the interaction of the biomaterial with the immune system. Studies involving the biofunctionalization of Ti implants with the response of cells of the immune system, both human and animal, especially in the initial stages of the post-implantation process, are scarce, with most of the analyzes carried out strictly in vitro. Thus, given the immunomodulatory role of Ti and the possible changes in the surface of this material, it is crucial to understand the inflammatory process that precedes osseointegration and to associate it with possible clinical outcomes, which culminate in the success or failure of the implant.
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