Role of CD-8 Population in Mononuclear Bone Cells (BMC) on Tissue Engineered Bone Defect Healing by Utilisation of a Modified Membrane Technique

• Applicant: Privatdozent Dr. Christoph Nau
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 464606918

The technique of the induced membrane is a well established procedure to cure critical size bone defects. It is based on a foreign body reaction which leads to this induced membrane surrounding a PMMA cement spacer. After extraction of this spacer the corresponding defect can be filled with autologous bone graft alone or in combination with bone graft substitutes. We could already emphasize the role of mononuclear bone cells on bone defect healing in combination with the induced membrane technique. We could show that BMC seeded on β-TCP or demineralized bone matrix leads to equivalent bone healing compared to autologous bone. The substitution of the induced membrane by an artificial construct is a possibility to reduce the two stage to a single stage operation. Initial experiments with the use of a decellularized dermis and autologous bone were promising and a healing comparable to the Masquelet technique could be observed. A potential mechanism could be the barrier function of the dermis which inhibits the ingrowth of fibrotic tissue and the dislocation of the inserted cancellous bone. In not yet published experiments it could be seen that decellularized dermis seeded with BMC led to an impairment of bone healing. BMC, a mixture of different mononuclear cells, include CD 8 T-cells of which the terminally differentiated subpopulation effect bone healing negatively. Considering the high amount of BMC, the presence of CD 8 positive T-cells and the inhibiting effects of CD 8term positive cells on bone healing we hypothesize that the observed negative effects on critical size defect healing by using the one stage membrane technique seeded with BMC is caused by a high amount of CD 8term T-cells. This inhibits the positive effects of other cell populations (e.g. mononuclear cells) in BMC by prolonging the inflammation which causes a delayed bone union. Therefore, the depletion of the CD 8term population could lead to an improvement of the one stage membrane technique with avoidance of autologous bone transplantation. The aim of this project is the optimization of the BMC augmented one stage membrane technique. This is performed by elucidating the role of the CD 8 positive T-cell population in BMC on bone healing under consideration of cellular and humoral aspects and by a better understanding of the effect mechanism of the decellularized dermis.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dirk Henrich, Ph.D.