BSRT Graduate School

Project 8

The immuno-capacity of the human bone marrow in context of arthroplasty

 
Track: 
Biology track
Supervisor 1: 
Geissler, Sven
Supervisor 2: 
Perka, Carsten
Supervisor 3: 
Melanie Ort

 

In an aging society, arthroplasty has made an invaluable contribution to enabling painless mobility even at an advanced age. Despite the overall great success of joint replacements, there are several reports showing serious complications caused by implant-derived metal particles. Possible reasons are that (1) the altered biology of the mostly elderly patients is not sufficiently considered and (2) the general interactions between the implant, implant-derived metallic wear and corrosion products and the biological environment are poorly understood. Local exposure to metallic debris leads to adverse reactions including osteolysis and impaired bone homeostasis, resulting in revision surgery with inferior outcomes compared to primary surgery. This aseptic osteolysis occurs in close proximity to the implant surface, but little is known about the extent of the metallic exposure at the peri-implant bone & bone marrow and its effects on the biology of this tissues. We want to investigate blood, bone & bone marrow biopsies from patients with total joint im-plants to evaluate (1) the extent of the metallic exposure and (2) the associated biological alterations in terms of matrix structure and cellular composition of peri-implant bone & bone marrow. We will also use a microfluidic 3D culture system to (1) simulate different metallic exposure scenarios and analyse the resulting biological effects, and (2) evaluate the reversibility of exposure-related bone loss using defined therapeutic approaches.

 

During the project the following techniques should be learned:

- Modern (3D) imaging techniques - Multicolor flow cytometry

- Isolation, cultivation and functional characterization of primary human cells

- 3D organ-on-a-chip models for bone/bone marrow

- Immunohistology - Multiplex ligand assays

 

References

 

1. Ort MJ, Geissler S, Rakow A, Schoon J. The Allergic Bone Marrow? The Immuno-Capacity of the Human Bone Marrow in Context of Metal-Associated Hypersensitivity Reactions. Front Immunol. 2019. 18. 10:2232.

 

2. Schoon J, Hesse B, Rakow A, Ort MJ, Lagrange A, Jacobi D, Winter A, Huesker K, Reinke S, Cotte M, Tucoulou R, Marx U, Perka C, Duda GN, Geißler S. Metal-Specific Biomaterial Accumulation in Human Peri-Implant Bone and Bone Marrow. Adv. Sci. 2020. DOI: 10.1002/advs.202000412. In Press