BSRT Graduate School

Project 6

Mechano-sensation of angiogenesis and callus formation in early bone regeneration

 
Track: 
Biology track
Supervisor 1: 
Duda, Georg
Supervisor 2: 
Gerhardt, Holger

 

In our group “Angiogenesis and Immuno-Mechanics” we are as an international and interdisciplinary team unraveling basic mechano-biological principles of early tissue self-assembly as essential drivers for tissue regeneration. We could successfully translate earlier findings into clinical applications in patients suffering from delayed bone healing.

 

We are seeking a young talent to unravel the basic mechano-biological principles of angiogenesis in bone healing. In bone healing and any other regenerative process nutrition supply and thus vessel ingrowth is essential after injury. To initiate angiogenesis, the initial pro-inflammatory phase that follows injury has to be completed, macrophages start to re-arrange the hematoma and fibroblasts initiate a self-assembly to form an early callus tissue. This is the starting point of healing in which callus and vascular growth team up. Surprisingly, both processes are highly orchestrated by mechanical cues but of different origins. While angiogenesis appears to be driven by inner vessel mechanics, the mechanical loads that act at a fracture drive the self-assembly of fibroblasts and the network of fibronectin and collagen that they form at the very start of healing. We have been able to document the mechano-sensation of both processes but how their mechano-responsiveness intermingle with each other remains so far unknown.

 

Within this PhD we aim at unraveling the key cell-cell interactions in early cell-matrix self-assembly and on forces exerted by either blood flow or extrinsic loading and their consequences for bone marrow reconstitution. We aim at combining a novel imaging technology that allows to visualize longitudinally the process of angiogenesis and collagen network formation during the early phases of healing. We assume that YAP/TAZ signaling of endothelial cells is modulated in its mechano-sensitivity during early healing but affected in its capability to control the self-assembly by advanced age or immune experience.

 

 

References 

 

1. Sass FA, Schmidt-Bleek K, Ellinghaus A, Filter S, Rose A, Preininger B, Reinke S, Geissler S, Volk HD, Duda GN, Dienelt A. CD31+ Cells from Peripheral Blood Facilitate Bone Regeneration in Biologically Impaired Conditions Through Synergistic Combined Effects on Immunomodulation and Angiogenesis. J Bone Miner Res. 2017 May;32(5):902-912.

 

2. Schmidt-Bleek K, Kwee BJ, Mooney DJ, Duda GN. Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis. Tissue Eng Part B Rev. 2015 Aug;21(4):354-64.