Development, characterization and in vivo assessment of a chitosan-simvastatin film for titanium coating: evaluation of the osseointegration potential under influence of nicotine

Abstract

The osseointegration under systemic modification by nicotine remains a great challenge to implantology, since the bone reparative potential of resident cells is negatively influenced in the presence of this factor. In this research project, the objective is to develop a chitosan-simvastatin coat on the surface of titanium in order to modulate and optimize the peri-implant repair process in models of systemic compromise by nicotine. Different techniques of functionalization with chitosan and incorporation of simvastatin will be applied aiming to obtain the best stability and modulatory potential for the coating. Initially, different methods of hydroxylation and functionalization with chitosan will be tested to achieve a stable chitosan-coating, for further addition of simvastatin in different concentrations (0.1, 1 and 2 µM) in order to determine its release rate (phase 1). After stablishing the best formulation in Phase 1, cells of the osteoblastic lineage will be seeded over the discs to evaluate cell availability and proliferation, adhesion and spreading, migration, mineralized matrix deposition, and ALP activity (phase 2). In Phase 3, initially, the dosage of nicotine capable to alter the ability of bone cells to deposit mineralized matrix will be determined. Up to two coating formulations obtained in phase 2 will be tested. For that, cells of the osteoblastic lineage will be seeded over the discs in culture media in the presence or absence of nicotine. Finally, the coating that displays the best results in vitro under degenerative stimulus (phase 3) will be tested in a model of implant placement in the tibiae of rats previously exposed to nicotine in order to access the isolate potential of the coating against the influence of this substance. The specimens will be collected and processed for histometry of contact and area, histology, immunohistochemistry, and ultrastructural analysis of the interface bone/implant (phase 4). (AU)