Angiogenesis and Immunomechanics
Healing begins with the self-organisation of cells in the wound to reestablish structured tissue and restore the mechanical stability and intrinsic pretension of the injured matrix lost through the injury. Our aim is to decipher this independent organisation of fibroblasts, vascular precursors, immune cells and mechanical instability in the complex environment of the tissue. A better understanding of this interplay forms the basis for novel therapeutic approaches in musculoskeletal regeneration.
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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.
In Collaboration with Holger Gerhardt
- Authors:Bucher C, Schlundt C, Wulsten D, Sass F, Wendler S, Ellinghaus A, Thiele T, Seemann R, Willie B, Volk H, Duda G, Schmidt-Bleek KJournal:Front Immunol Year:2019; Volume:10:Pages:797.
- Authors:Kruck B, Zimmermann EA, Damerow S, Figge C, Julien C, Wulsten D, Thiele T, Martin M, Hamdy R, Reumann MK, Duda GN, Checa S, Willie BM
Journal:J Bone Miner Res Year:2018; Volume:33Issue:(9):Pages:1686-1697.
Title:Sclerostin Neutralizing Antibody Treatment Enhances Bone Formation but Does Not Rescue Mechanically Induced Delayed Healing
- Authors:Yang H, Albiol L, Chan WL, Wulsten D, Seliger A, Thelen M, Thiele T, Spevak L, Boskey A, Kornak U, Checa S, Willie BM
Journal:J Biomech Year:2017; Volume:65:Pages:145-153.
Title:Examining tissue composition, whole-bone morphology and mechanical behavior of Gorab(Prx1) mice tibiae: A mouse model of premature aging
- Authors:Pflanz D, Birkhold AI, Albiol L, Thiele T, Julien C, Seliger A, Thomson E, Kramer I, Kneissel M, Duda GN, Kornak U, Checa S, Willie BM
Journal:Sci Rep Year:2017; Volume:7Issue:(1):Pages:9435.
Title:Sost deficiency led to a greater cortical bone formation response to mechanical loading and altered gene expression
- Authors:Willie BM, Birkhold AI, Razi H, Thiele T, Aido M, Kruck B, Schill A, Checa S, Main RP, Duda GN
Journal:Bone Year:2013; Volume:55Issue:(2):Pages:335-46.
Title:Diminished response to in vivo mechanical loading in trabecular and not cortical bone in adulthood of female C57Bl/6 mice coincides with a reduction in deformation to load