Characterization of the adsorbed protein layer on orthopedic biomaterials and its regenerative potential after initial patient contact

• Applicant: Dr. Andrea Sowislok
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 528251468

In human bone, biomaterials such as bone substitutes and metallic implants are used to replace the function of supporting and moving organs (endoprostheses, plates, intramedullary nails, etc.). The so-called cementless anchorage of these materials results in a direct interaction with the bony implant site and thus influences local bone remodeling (regeneration, resorption). Rapid stimulation of new bone formation at the biomaterial interface is a prerequisite for healing with early reloading. The local humoral and cellular mechanisms in situ that occur after the first intraoperative bone contact until load-stable osseointegration are complex and not yet fully elucidated in detail. They follow a strict sequence of protein adsorption, cellular migration, proliferation, biomineralization and subsequent bone remodeling processes. Knowing the exact composition of the protein layer adsorbed to the biomaterial in situ, even within minutes, can help to understand and predict the subsequent response of the bony microenvironment to the biomaterial surface. In preliminary work, we have already disproved the hypothesis in the literature of immediate binding of plasma proteins to the implant surface, since most of the proteins adsorbed to the hip stems were of intracellular origin and only 9% could be assigned to the plasma proteome. Moreover, an incubation time in the range of minutes is not relevant for the quality and quantity of this protein layer. Differences in the protein composition were mainly found on different implant surfaces, suggesting changes in the adsorbed protein layer on different materials. However, it is still unknown whether there is a "basic implantome" that is not patient- and material-specific. In addition, the effects of a longer incubation period and a lower temperature on the protein composition have not yet been studied in detail. In this application, we are introducing an experimental intermediate stage between the patient and the laboratory. In addition, we will investigate whether proteins adsorbed to the biomaterial stimulate osteogenic differentiation of mesenchymal stromal cells (MSCs), potentially promoting osseointegration.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Marcus Jäger