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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 1 - Principal Investgators

PD Dr. Katharina Schmidt-Bleek

CRC 1444 Deputy Scientific Coordinator & Implementation of 3R principles, Subprojects 1 & 12 | RU 2165 Subprojects 5 & 6

Katharina Schmidt-Bleek
Prof. Dr. Hans-Dieter Volk

CRC 1444 Deputy Spokesperson & Ombudsperson, Subprojects 1 & 2 | RU Subproject 5

Understand and reshape the impact of an experienced adaptive immunity on fracture healing

The interaction between the immune system and bone metabolism is now very well documented. Schmidt-Bleek and Volk were able to show that the composition of the adaptive immune system, in particular the ratio of naïve and effector memory T cells have a decisive influence on bone regeneration. The immunological age determines the inflammatory reaction that initiates the bone healing process. A high proportion of effector memory T cells results in a cytokine environment that is detrimental to healing. In pre-clinical models close to the clinic, it has been shown that targeted countermeasures using local immunomodulatory approaches achieve an improvement in bone regeneration.

A current focus is the development of novel therapeutic concepts to target local immunomodulation in the early phase of bone regeneration. Currently, immunomodulatory implants and mRNA-based approaches are in the "proof of concept" phase.

Most important results

Microbiome diversity

Inflammatory Response | Energy Supply & Consumption

Analysis of the gut microbiome showed substantial alterations post-surgery due to differences in the level of immunological experience.

Bucher et al. Exp. Mol. Med. 2022

Support of Angiogenesis

Inflammatory Response | Energy Supply & Consumption

Multimodal mRNA-modified cell implants for local support of angiogenesis .

Drzeniek et al. Biomaterials 2023 | In collaboation with subproject P05 

Immune modulation

Inflammatory Response | Energy Supply & Consumption

mRNA technology for immunomodulation and its pro-inflammatory side effects.

Multifaceted roles of macrophages

Energy Supply & Consumption | Force Transmission & Sensing

Macrophages and their phenotype are essential for the revascularization steps in bone healing / biomechanics incfluence macrophage polarization.

Schlundt et al Acta Biomater. 2021 | In collaboration with subproject P09 

Inflammatory cytokines

Inflammatory Response | Force Transmission & Sensing

Inflammatory cytokines direct ECM deposition in vitro.

In collaboration with subprojekt P03 


Dr. Christian Bucher (Postdoc)

Deciphering and modulating cellular communication in fracture healing with a focus on altered processes due to aging

Norman Drzeniek (Clinician Scientist)

Next generation MSCs for regenerative purposes - manipulation of the cellular phenotype using biomaterials and non-viral gene transfer

M.Sc. Ann-Kathrin Meß (Doctoral Researcher)

Regulatory T cells - the role of phenotypical properties during bone healing and regeneration

Carolin Paschke (Doctoral Researcher until 08/2022)

Understand and reshape the impact of obesity/type 2 diabetes mellitus and adaptive immunity on bone fracture healing






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