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
CRC 1444 Deputy Scientific Coordinator & Implementation of 3R principles, Subprojects 1 & 12 | RU 2165 Subprojects 5 & 6
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.
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
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
Team
Deciphering and modulating cellular communication in fracture healing with a focus on altered processes due to aging
Next generation MSCs for regenerative purposes - manipulation of the cellular phenotype using biomaterials and non-viral gene transfer
Regulatory T cells - the role of phenotypical properties during bone healing and regeneration
Understand and reshape the impact of obesity/type 2 diabetes mellitus and adaptive immunity on bone fracture healing
Publications
- Authors:Drzeniek, N. M.; Kahwaji, N.; Schlickeiser, S.; Reinke, P.; Geissler, S.; Volk, H. D.; Gossen, M.
Journal:Biomaterials Year:2023; Volume:294:Pages:121971.
Title:Immuno-engineered mRNA combined with cell adhesive niche for synergistic modulation of the MSC secretome - Authors:Duda, G. N.; Geissler, S.; Checa, S.; Tsitsilonis, S.; Petersen, A.; Schmidt-Bleek, K.
Journal:Nat Rev Rheumatol Year:2023; Volume:19Issue:(2):Pages:78-95.
Title:The decisive early phase of bone regeneration - Authors:Schlundt, C.; Fischer, H.; Bucher, C. H.; Rendenbach, C.; Duda, G. N.; Schmidt-Bleek, K.
Journal:Acta Biomater Year:2021; Volume:133:Pages:46-57.
Title:The multifaceted roles of macrophages in bone regeneration: A story of polarization, activation and time
