
Research Unit "Regeneration in aged"
The Research Unit 2165 Regeneration in Aged Individuals: Using Bone Healing as a Model System to Characterise Regeneration under Compromised Conditions aims to understand the basic mechanisms that impede the otherwise effective healing process along the two pathways of early immune response and restoration of mechanical competence through aging.
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Project 1 - Principal Investgators
CRC 1444, Spokesperson & Scientific Coordinator, Subprojects 8, 9, 13 & Central Administrative Project | RU 2165 Subproject 1


Mechano-dependency of early bone healing, angiogenesis, and their interplay across ages

The relevance of mechanical boundary conditions as driving factor in bone regeneration and adaptation is generally well accepted. In addition, functional angiogenesis and vascular supply of a fracture zone are also considered to be key factors in healing and in the viability of regenerated tissues. However, the relationship and interdependence between tissue mechanical conditions and angiogenesis is not yet well understood. Recent work has shown the critical role of extrinsic mechanics on the self-organization of fibroblast networks in early callus formation and endothelial cell-cell interactions as reaction to the blood flow driving vascular network formation. Pericyte and vascular smooth muscle cells confer stability and diameter control to nascent vessels. But how fibroblasts and/or pericytes relay mechanical input from surrounding callus tissue to adapt vascular patterning has not been studied. Our primary goal is to understand how mechanical loading influences functional vascular network formation and early callus organization in young and aged during bone healing. This work will help to unravel the age dependent signalling pathways between externally applied load, fibroblast self-organization, pericyte response, vascular network formation, and the early soft callus and bone marrow re-organization after injury.
Publications
- Authors:Vining, K. H.; Marneth, A. E.; Adu-Berchie, K.; Grolman, J. M.; Tringides, C. M.; Liu, Y. Wong, W. J.; Pozdnyakova, O.; Severgnini, M.; Stafford, A;. Duda, G. N.; Hodi, F. S.; Mullally, A.; Wucherpfennig, K. W.; Mooney, D. J.
Journal:Nat Mater Year:2022; Volume:21Issue:(8):Pages:939-950.
Title:Mechanical checkpoint regulates monocyte differentiation in fibrotic niches - Authors:Garske, D. S.; Schmidt-Bleek, K.; Ellinghaus, A.; Dienelt, A.; Gu, L.; Mooney, D. J.; Duda, G. N.; Cipitria, A.
Journal:Tissue Eng Part A Year:2020; Volume:26Issue:(15-16):Pages:852-862.
Title:Alginate Hydrogels for In Vivo Bone Regeneration: The Immune Competence of the Animal Model Matters - Authors:Lang, A.; Kirchner, M.; Stefanowski, J.; Durst, M.; Weber, M. C.; Pfeiffenberger, M.; Damerau, A.; Hauser, A. E.; Hoff, P.; Duda, G. N.; Buttgereit, F.; Schmidt-Bleek, K.; Gaber, T.
Journal:Acta Biomater Year:2019; Volume:86:Pages:171-184.
Title:Collagen I-based scaffolds negatively impact fracture healing in a mouse-osteotomy-model although used routinely in research and clinical application - Authors:Hoerth, R. M.; Kerschnitzki, M.; Aido, M.; Schmidt, I.; Burghammer, M.; Duda, G. N.; Fratzl, P.; Willie, B. M.; Wagermaier, W.
Journal:J Mech Behav Biomed Mater Year:2018; Volume:77:Pages:258-266.
Title:Correlations between nanostructure and micromechanical properties of healing bone - Authors:Schoon, J.; Geissler, S.; Traeger, J.; Luch, A.; Tentschert, J.; Perino, G.; Schulze, F.; Duda, G. N.; Perka, C.; Rakow, A.
Journal:Nanomedicine Year:2017; Volume:13Issue:(8):Pages:2415-2423.
Title:Multi-elemental nanoparticle exposure after tantalum component failure in hip arthroplasty: In-depth analysis of a single case - Authors:Cipitria, A.; Boettcher, K.; Schoenhals, S.; Garske, D. S.; Schmidt-Bleek, K.; Ellinghaus, A.; Dienelt, A.; Peters, A.; Mehta, M.; Madl, C. M.; Huebsch, N.; Mooney, D. J.; Duda, G. N.
Journal:Acta Biomater Year:2017; Volume:60:Pages:50-63.
Title:In-situ tissue regeneration through SDF-1alpha driven cell recruitment and stiffness-mediated bone regeneration in a critical-sized segmental femoral defect - Authors:Rosa, A.; Giese, W.; Meier, K.; Alt, S.; Klaus-Bergmann, A.; Edgar, L. T.; Bartels-Klein, E.; Collins, R. T.; Szymborska, A.; Coxam, B.; Bernabeu, M. O.; Gerhardt, H.
Journal:Development Year:2022; Volume:149Issue:(3)
Title:WASp controls oriented migration of endothelial cells to achieve functional vascular patterning - Authors:Ong, Y. T.; Andrade, J.; Armbruster, M.; Shi, C.; Castro, M.; Costa, A. S. H.; Sugino, T.; Eelen, G.; Zimmermann, B.; Wilhelm, K.; Lim, J.; Watanabe, S.; Guenther, S.; Schneider, A.; Zanconato, F.; Kaulich, M.; Pan, D.; Braun, T.; Gerhardt, H.; Efeyan, A.; Carmeliet, P.; Piccolo, S.; Grosso, A. R.; Potente, M.
Journal:Nat Metab Year:2022; Volume:4Issue:(6):Pages:672-682.
Title:A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth - Authors:Coxam, B.; Collins, R. T.; Hussmann, M.; Huisman, Y.; Meier, K.; Jung, S.; Bartels-Klein, E.; Szymborska, A.; Finotto, L.; Helker, C. S. M.; Stainier, D. Y. R.; Schulte-Merker, S.; Gerhardt, H.
Journal:Development Year:2022; Volume:149Issue:(6)
Title:Svep1 stabilises developmental vascular anastomosis in reduced flow conditions - Authors:Zeinali, S.; Thompson, E. K.; Gerhardt, H.; Geiser, T.; Guenat, O. T.
Journal:APL Bioeng Year:2021; Volume:5Issue:(2):Pages:026102.
Title:Remodeling of an in vitro microvessel exposed to cyclic mechanical stretch - Authors:Vion, A. C.; Perovic, T.; Petit, C.; Hollfinger, I.; Bartels-Klein, E.; Frampton, E.; Gordon, E.; Claesson-Welsh, L.; Gerhardt, H.
Journal:Front Physiol Year:2020; Volume:11:Pages:623769.
Title:Endothelial Cell Orientation and Polarity Are Controlled by Shear Stress and VEGF Through Distinct Signaling Pathways - Authors:Vion, A. C.; Alt, S.; Klaus-Bergmann, A.; Szymborska, A.; Zheng, T.; Perovic, T.; Hammoutene, A.; Oliveira, M. B.; Bartels-Klein, E., Hollfinger, I.; Rautou, P. E.; Bernabeu, M. O.; Gerhardt, H.
Journal:J Cell Biol Year:2018; Volume:2017Issue:(5):Pages:1651-1665.
Title:Primary cilia sensitize endothelial cells to BMP and prevent excessive vascular regression - Authors:Neto, F.; Klaus-Bergmann, A.; Ong, Y. T.; Alt, S.; Vion, A. C.; Szymborska, A.; Carvalho, J. R.; Hollfinger, I.; Bartels-Klein, E.; Franco, C. A.; Potente, M.; Gerhardt, H.
Journal:Elife Year:2018; Volume:7:Pages:e31037.
Title:YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development