Biological factors involved in the osseointegration of oral titanium implants with different surfaces: a pilot study in minipigs

BACKGROUND: The stability of titanium implants is determined by the rigid load-bearing connections that are formed by the bone, a process that involves a complex network of cells, pro- and anti-inflammatory mediators, and growth factors. The osseointegration processes at the interfaces of machined and porous implants were studied using molecular and histological techniques. METHODS: Two machined and two porous titanium implants were inserted into the tibiae of four minipigs. The animals were sacrificed at 15, 30, 60, and 90 days post-implantation. The levels of bone morphogenetic protein (BMP)-4, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha were quantified in the peri-implant osseous samples. The levels of interleukin (IL)-1beta, IL-6, IL-10, and TNF-alpha in the serum were also assessed. RESULTS: Histomorphological analysis showed evidence of bone ossification around the porous implant at 60 days. Surrounding the machined implants, highly sclerotic fibrous pads started the healing response at 90 days, and the levels of TGF-beta1 and BMP-4 began to increase at 60 days, at which time bone ossification around the porous implants was already evident. TNF-alpha was not present in the bone next to the implants. The serum levels of cytokines IL-1beta, IL-6, and IL-10 were not increased. The serum level of TNF-alpha increased during the healing process. CONCLUSIONS: We observed that the levels of BMP-4 and TGF-beta1, which play essential roles in the osteogenesis process, increased earlier around the porous implants than around the machined implants. Similarly, the ossification process was initiated earlier at the surfaces of the porous implants than at the surfaces of the machined implants.