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DFG Collaborative Research Centre 1444

This Collaborative Research Centre aims to unravel the basic mechanisms that differentiate between success and failure in regeneration of musculoskeletal tissue using bone healing as a role model.

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Subproject 16 - Principal Investgators

Dr. Sven Geißler

CRC 1444 Subprojects 5 & 16 | RU 2165 Subproject 2

Promoting humeral head fracture healing by local immunomodulation - A phase I/IIa, prospective, mono-centre, randomized, open labelled, controlled study

The process of fracture healing begins with a pro-inflammatory response that involves the activation and accumulation of immune cells at the site of injury and the production of high levels of cytokines such as TNF and IFN. The timely resolution of this acute inflammation is critical for the subsequent healing phases in which the original architecture of the damaged tissue is restored. T cells are important modulators of endogenous regeneration, and inadequate fracture healing in humans correlates significantly with elevated levels of circulating CD8+ effector memory T cells, which locally maintain an inflammatory environment and delay tissue regeneration. A local pharmacological treatment designed to modulate the balance between CD8+ effector and CD4+ regulatory T cells to promote healing is being tested in a current phase I/IIa clinical trial (IloBone). Mechanistic studies are also being performed to better understand the role of injury-related inflammatory processes in other tissues (e.g. cartilage, tendon or muscle) and to investigate the mode of action of other therapeutic approaches. This including exploratory efficacy studies on cell-based therapies or (already clinically used) immunomodulatory interventions, such as the use of platelet-rich plasma.

Ilobpone Study

A phase I/IIa, prospective, mono-center, randomized, open labeled, controlled study to assess the safety and efficacy of applying Iloprost locally in the fracture site to promote bone healing in patients with proximal humeral fracture
Sponsor Protocol Code: SIFU17
EudraCT Number: 2017-003813-24

Most important results

The influence of circulating and local immune cells on tissue regeneration

Inflammatory Response | Energy Supply & Consumption

We are investigating how the systemic and local immune cell composition influences the initial inflammatory response and the process of tissue healing. Our study provides new insights into the immunology of the human bone marrow and its involvement in orthopedic conditions.

Bucher et al. Exp Mol Med. 2022 | In collaboration subproject P01 and the central service project C01

Cell-based approaches to enhance musculoskeletal regeneration

Inflammatory Response | Energy Supply & Consumption

Fundamental understanding of their regenerative function, their interaction with the injury microenvironment and their impairment by adverse conditions are essential for effective application of cell-based therapies.

Kotsaris G et al. NPJ Regen Med. 2023 | In collaboration with subproject P04

Hochmann et al. Sci Transl Med. 2023 | In collaboration with subprojects P01, P02 and  P05

Drzeniek NM et al. Biomaterials. 2023 | In collaboration with subproject P01

Brachtl et al. Cells. 2022 | In collaboration subprojects with P01 and P05

Drzeniek NM et al. Biofabrication. 2021 | In collaboration with subproject P01

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Quality and efficacy of platelet-rich plasma (PRP) therapies

Inflammatory Response | Energy Supply & Consumption

Platelet-rich plasma (PRP) therapy is a promising approach for the treatment of musculoskeletal disorders such as tendinopathies and osteoarthritis (OA). The composition of PRP is determined by the immune cell and cytokine profile of the donor and the method of preparation, which affects its efficacy.

Niemann et al. Arthritis Research & Therapy 2023 | In collabroation with the central service project C01

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Initial immune reactions during joint inflammation

Inflammatory Response | Energy Supply & Consumption

Rheumatoid arthritis is a chronic disease in which the immune system attacks and damages joint tissue. To study the interactions between immune and tissue cells at the onset of the disease, we have established an animal model of collagen antibody-induced arthritis (CAIA).

Maleitzke et al. STAR Protoc.2022 | In collaboration with subproject P15

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The infrapatellar fat pad as a source of inflammation in knee osteoarthritis (OA) and its interactions with the surrounding joint tissue

Inflammatory Response | Energy Supply & Consumption

The infrapatellar fat pad (IFP) may play a role in knee OA by influencing cartilage inflammation, degradation and repair. We describe the complex relationships between the IFP and adjacent tissues. This may provide a better understanding of the causes and targeted treatments of knee OA.

Zhou et al. J Orthop Res. 2022

Reducing Donor Site Morbidity for Autologous Chondrocyte Implantation

Inflammatory Response | Energy Supply & Consumption

Osteochondritis dissecans (OCD) is a condition in which fragments of cartilage (loose bodies (LBs) become completely detached from the joint. However, these LBs could be used for autologous chondrocyte implantation (ACI) to repair the cartilage defects.

Textor M et al. Int J Mol Sci. 2023 | In Zusammenarbeit mit Teilprojekt P05 und dem Zentralen Service Projekt C01


Ioanna Maria Dimitriou (Doctoral Researcher)

Shaping the inflammatory injury response: Clinical validation of Iloprost as a local immune modulation strategy to enhance bone regeneration - IloBone a phase I/IIa study

Alexander Hildebrand (Clinician Scientist)

Osteoarthritis and Aniogenesis

Luis Lauterbach (Scientist)

Ilobone Study | Knee Osteoarthritis (OA)

Dr. Tazio Maleitzke (Clinician Scientist)

Joint Inflammmation | Knee Osteoarthritis

Lukas Mödl (Doctoral Researcher)

Ilobone Study

Dr. Marcel Niemann (Clinician Scientists)

Immune Cells & Tissue Regeneration | Platelet Rich Plasma (PRP) Therapies

Anne Zergiebel (Clinical Trial Coordinator)

Ilobone Study

Sijia Zhou (Doctoral Researcher)

Mechanism of Regenerative Cell Action in Osteoarthritis






Founded by the DFG (Project Number: 427826188)
Funding Period 2021-2024