The human implant proteome - docking site for local cells, tissue glue and prerequisite for osteointegration

Objectives Orthopaedic implants designed for permanent in vivo application require a high degree of biocompatibility and mechanical stability. Furthermore, cementless fixed components of artificial joints call for rapid osseointegration and sufficient load transfer. Here, the preconditioning protein film adhered onto the implant's surface during implantation plays a crucial role for further cellular reactions such as adherence, migration and differentiation. We analyzed the local changes of protein composition at two kinetic points in order to get a deeper understanding of the dynamic process of human in vivo protein binding on femoral stem explants.

Methods 12 patients (3 male, 9 female, mean age 73.5±7.3 years) with advanced osteoarthritis qualified for total hip replacement were enrolled in this prospective study. The surgical procedure was highly standardized (single surgeon study, Harding-Bauer approach) and applied in an academic level I arthroplasty center. One implant type of titanium hip stems were inserted cementless into the femoral canal until contact fixation to surrounding bone was achieved. The implants were removed after 2 (n=6) or 5 minutes (n=6) in situ . Proteins were removed from the two different surfaces of the Ti6Al4V femoral stems (prox. rough, distal smooth) and the proteome was analyzed essentially as described in [1] with some minor modifications.

Results and Conclusion The protein content was much higher on the rough surface with 226.7 ± 111.2 µg per implant compared to 26.9±18.8 µg on the smooth surface (p < 0.001). First preliminary data suggest that the protein layer adhered onto the implants showed a kinetic-and surface-dependent composition. Several proteins were detectable after 2 min, but not detected anymore after 5 min, possibly indicating transient adherence. In addition, several proteins were only detectable after 5 min, indicating slower kinetics of adherence. However, we did not document relevant changes within the top 40 proteins adhered onto the surfaces.

Transient changes (when comparing 2 and 5 min) were more pronounced in the case of smooth surface, possibly indicating that the quantitative protein layer in rough surfaces is more stable than in smooth surfaces. There was no correlation between the molecular weight and the changes in the proteome for the rough and the smooth surface. The charge of the proteins was not correlated to its incidence on the implant, independent from surface or insertion time. For the first time we demonstrated protein changes in situ onto a cementless titanium hip stem. The implant proteome is a new and promising research area. This missing link between understanding the in situ surface chemistry of implants and the associated osteobiology of the surrounding tissue may lead to innovative implant designs.

[1] Jäger, Jennissen, Haversath, Busch, Grupp, Sowislok, Herten M. Intra-surgical Protein Layer on Titanium Arthroplasty Explants: From the Big Twelve To The Implant Proteome. Proteomics Clin Appl. 2019:e1800168

Stichwörter proteome, implant, titanium, bone, osseointegration

Publication History

Article published online:
15 October 2020