SFB 1444:  Directed Cellular Self-Organization to Advance Bone Regeneration

• Subject Area: Medicine
• Term: since 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 427826188

The CRC 1444 focuses on advancing musculoskeletal health through its research program on guided cellular self-organization to promote endogenous bone regeneration. This initiative addresses the significant burden that musculoskeletal injuries, diseases, and disorders impose on healthcare systems worldwide, surpassing even major chronic conditions like circulatory diseases and cancer in prevalence. The research in the CRC 1444 is based on the remarkable endogenous regenerative capacity of bone, which restores structural integrity and functionality through a dynamic interplay between various biomechanical, cellular and molecular factors. Unlike almost all other tissues, bone can heal without scarring even after severe injury, making it an ideal model to study endogenous regeneration cascades, especially under challenging conditions. In the first funding period, the CRC elucidated and validated key mechanisms in bone healing and highlighted the critical roles of the inflammatory response, biomechanical status, metabolic state and their interactions in early cellular self-organization and successful healing. This fundamental research underscored the importance of developing personalized treatment strategies that specifically address accompanying health conditions such as advanced age, diabetes or obesity, focusing on patient-specific biology to prevent complications such as delayed or incomplete bone healing. Building on these achievements, the CRC 1444 now aims to broaden its scope of research to investigate how compromised healing conditions, including overwhelming inflammation, diminished mechano-sensing, and impaired metabolism, alter the fundamental mechanisms of regeneration. The CRC 1444's overarching hypothesis is that early phase of bone regeneration already determines the long-term healing success. This postulates that delayed or impaired healing is initiated and driven by altered immune responses, metabolic dysregulation, and impaired mechano-sensation during these early stages. In its second funding period, the CRC 1444 plans to integrate expertise in spatial transcriptomics, single-cell analysis, and bioengineering model systems to decipher the spatial and temporal dynamics of cellular interactions critical for effective bone healing, particularly in challenging conditions such as immune-aging or type 2 diabetes mellitus. This multidisciplinary approach aims to develop personalized therapeutic strategies tailored to individual patient characteristic, enhancing healing outcomes and optimizing healthcare resource utilization.

• DFG Programme: Collaborative Research Centres

Current projects

• C01 - Central Service Project – Cell and Tissue Harvesting: Supply of functionally and immunologically characterized human samples for the CRC research projects (Project Heads Perka, Carsten ;  Reinke, Simon )
• C02 - Central Administrative Project ‐ Central tasks of the Collaborative Research Centre (Project Head Duda, Georg )
• P01 - Decoding and harnessing the impact of immune‐experience on the spatio‐temporal cellular interaction networks underlying bone healing (Project Heads Haas, Simon ;  Schmidt-Bleek, Katharina ;  Volk, Hans-Dieter )
• P02 - Clarifying the epigenetic control mechanisms of the bone regenerative capacity in MSCs to tap new cell sources for adoptive cell therapy (Project Heads Geißler, Sven ;  Polansky-Biskup, Julia ;  Volk, Hans-Dieter )
• P03 - Interplay of micro‐engineered mechanical signals and BMP/TGFb signaling in the context of bone healing (Project Heads Knaus, Petra ;  Petersen, Ansgar )
• P04 - The mechano‐genomic code: pioneer factors as decision makers (Project Heads Knaus, Petra ;  Mundlos, Stefan )
• P06 - From prediction to validation: Mechanical factors of impaired fracture healing in humans (Project Heads Trepczynski, Adam ;  Zachow, Stefan )
• P07 - The role and re‐establishment of internal tissue tension in normal versus compromised‐healing bone (Project Head Zaslansky, Paul )
• P09 - Mechano‐dependency of early bone healing, angiogenesis, and inflammation (Project Heads Duda, Georg ;  Gerhardt, Holger )
• P10 - Spatiotemporal regulation of sprouting angiogenesis through combined mechanical and geometrical cues (Project Heads Checa, Sara ;  Petersen, Ansgar )
• P11 - Harnessing bone macrophage and osteoclast programs and function to promote bone regeneration (Project Heads Diefenbach, Andreas ;  Triantafyllopoulou, Antigoni )
• P12 - Bone marrow adipose tissue: Harnessing metabolic regulation to shape bone maintenance and regeneration (Project Heads Schmidt-Bleek, Katharina ;  Schulz, Tim J. )
• P13 - Understand and shape bone regeneration by cellular metabolic adaptation in immune and stromal cells (Project Heads Duda, Georg ;  Sawitzki, Birgit )
• P14 - Defining microenvironmental cues governing myeloid functions during bone regeneration in situ and in vivo. (Project Heads Hauser, Anja Erika ;  Niesner, Raluca Aura )
• P15 - Impact of the central nervous system on metabolic and immunological responses, particularly focusing on adrenergic signaling and circadian rhythm in bone and fracture following trauma (Project Heads Jahn, Denise ;  Pumberger, Matthias ;  Tsitsilonis, Ph.D., Serafeim )
• P16 - Personalized fracture care combining patient stratification and targeted immunomodulatory therapy to prevent poor bone healing ‐ The PRECISION study (Project Heads Geißler, Sven ;  Winkler, Tobias )
• P17 - Deciphering the cellular crosstalk underlying the early stage of human fracture healing by leveraging a biomimetic engineering strategy (Project Heads Bolander, Ph.D., Johanna ;  Haas, Simon )

Completed projects

• P05 - Effects of implant-derived metal debris on bone formation and resorption (Project Heads Geißler, Sven ;  Perka, Carsten )
• P08 - Hydrogels with spatial patterning of biophysical and biochemical properties to guide osteogenesis (Project Heads Cipitria, Ph.D., Amaia ;  Duda, Georg )

• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Participating University: Freie Universität Berlin
• Participating Institution: Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE); Max-Delbrück-Centrum für Molekulare Medizin (MDC); Max-Planck-Institut für Kolloid- und Grenzflächenforschung; Wissenschaftspark Potsdam-Golm; Zuse-Institut Berlin (ZIB)
• Spokesperson: Professor Dr.-Ing. Georg Duda