Osseointegration around dental implants biofunctionalized with TGFß-1 inhibitor peptides: an in vivo study in beagle dogs.

The aim of this study was to evaluate the effect of biofunctionalization with two TGF-ß1 inhibitor peptides, P17 and P144, on osseointegration of CP-Ti dental implants. A total of 36 implants (VEGA, Klockner®) with 3.5 × 8 mm internal connection were used in this study, divided in three groups: (1) control group (n = 12), (2) implants which surfaces were biofunctionalized with P17 peptide inhibitor (n = 12), (3) implants with surfaces biofunctionalized by P144 peptide (n = 12). Three implants, one from each group, were inserted in both hemimandibles of 6 beagle dogs, 2 months after tooth extraction. Two animals were sacrificed at 2, 4 and 8 weeks post implant insertion, respectively. The samples were analyzed by Backscattering Scanning Electron Microscopy (BS-SEM) and histological analysis. Histomorphometric analysis of bone to implant contact (BIC), peri-implant bone fraction (BF) and interthread bone (IB) were carried out. Bone formation around implants measured by quantitative analysis, BS-SEM, was significantly higher in the P17-biofunctionalized implants, 4 and 8 weeks after the implantation. Histomorphometric analysis of BIC, BF and IB showed higher values in the P17-biofunctionalized group at initial stages of healing (2 weeks) and early osseointegration both at 4 and 8 weeks. For P144 biofunctionalized implants, the histomorphometric values obtained are also higher than control group. Accordingly, better results in the experimental groups were proven both by the quantitative and the qualitative analysis. Surface biofunctionalization with TGF-ß1 inhibitor peptides, P17 and P144, resulted in better quantitative and qualitative parameters relative to implant osseointegration.

Biofunctionalization with a TGFß-1 Inhibitor Peptide in the Osseointegration of Synthetic Bone Grafts: An In Vivo Study in Beagle Dogs.

OBJECTIVES: The aim of this research was to determine the osseointegration of two presentations of biphasic calcium phosphate (BCP) biomaterial-one untreated and another submitted to biofunctionalization with a TGF-ß1 inhibitor peptide, P144, on dental alveolus. Materials and Methods: A synthetic bone graft was used, namely, (i) Maxresorb® (Botiss Klockner) (n = 12), and (ii) Maxresorb® (Botiss Klockner) biofunctionalized with P144 peptide (n = 12). Both bone grafts were implanted in the two hemimandibles of six beagle dogs in the same surgical time, immediately after tooth extraction. Two dogs were sacrificed 2, 4, and 8 weeks post implant insertion, respectively. The samples were submitted to histomorphometrical and histological analyses. For each sample, we quantified the new bone growth and the new bone formed around the biomaterial's granules. After optical microscopic histological evaluation, selected samples were studied using backscattered scanning electron microscopy (BS-SEM). Results: The biofunctionalization of the biomaterial's granules maintains a stable membranous bone formation throughout the experiment timeline, benefitting from the constant presence of vascular structures in the alveolar space, in a more active manner that in the control samples. Better results in the experimental groups were proven both by quantitative and qualitative analysis. Conclusions: Synthetic bone graft biofunctionalization results in slightly better quantitative parameters of the implant's osseointegration. The qualitative histological and ultramicroscopic analysis shows that biofunctionalization may shorten the healing period of dental biomaterials.

In vitro cell response on CP-Ti surfaces functionalized with TGF-ß1 inhibitory peptides.

Osseointegration of implants is conversely related to the generation of a fibrous tissue capsule around the implant by the host environment. Although TGF-ß1 plays many roles in regeneration processes, it is the cytokine to be mostly associated to the production of fibrotic tissue and thus, its inhibition has demonstrated to be beneficial to prevent several fibrotic reactions. Surface biofunctionalization enables the immobilization of biologically active molecules on an implant surface to tailor the biological response of the host. Here, we studied in vitro biological effects of biofunctionalized CP-Ti surfaces with a TGF-ß1 inhibitor peptide, P144. A reliable biofunctionalization process that tethers P144 peptides to commercially pure titanium was developed. Differentiation of human mesenchymal stem cells, osteoblasts and fibroblasts on P144-functionalized and control surfaces was assessed at the gene expression and protein production levels. Results showed that P144-functionalized surfaces reduced expression and production of fibrotic differentiation markers and increased osteoblastic differentiation markers. Therefore, biofunctionalization of surfaces with TGF-ß1 inhibitor peptides are an alternative promising strategy for inducing osseointegration around medical devices and implants.