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External mechanical loading overrules cell-cell mechanical communication in sprouting angiogenesis during early bone regeneration
Citation Link: https://doi.org/10.15480/882.9186
Publikationstyp
Journal Article
Date Issued
2023-11-01
Sprache
English
Author(s)
TORE-DOI
Journal
Volume
19
Issue
11
Article Number
e1011647
Citation
PLoS Computational Biology 19 (11): e1011647 (2023)
Publisher DOI
Scopus ID
Publisher
PLoS
ISSN
1553734X
Peer Reviewed
true
Sprouting angiogenesis plays a key role during bone regeneration. For example, insufficient early revascularization of the injured site can lead to delayed or non-healing. During sprouting, endothelial cells are known to be mechano-sensitive and respond to local mechanical stimuli. Endothelial cells interact and communicate mechanically with their surroundings, such as outer-vascular stromal cells, through cell-induced traction forces. In addition, external physiological loads act at the healing site, resulting in tissue deformations and impacting cellular arrangements. How these two distinct mechanical cues (cell-induced and external) impact angiogenesis and sprout patterning in early bone healing remains however largely unknown. Therefore, the aim of this study was to investigate the relative role of externally applied and cell-induced mechanical signals in driving sprout patterning at the onset of bone healing. To investigate cellular self-organisation in early bone healing, an in silico model accounting for the mechano-regulation of sprouting angiogenesis and stromal cell organization was developed. Computer model predictions were compared to in vivo experiments of a mouse osteotomy model stabilized with a rigid or a semirigid fixation system. We found that the magnitude and orientation of principal strains within the healing region can explain experimentally observed sprout patterning, under both fixation conditions. Furthermore, upon simulating the selective inhibition of either cell-induced or externally applied mechanical cues, external mechanical signals appear to overrule the mechanical communication acting on a cell-cell interaction level. Such findings illustrate the relevance of external mechanical signals over the local cell-mediated mechanical cues and could be used in the design of fracture treatment strategies for bone regeneration.
DDC Class
610: Medicine, Health
Publication version
publishedVersion
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journal.pcbi.1011647.pdf
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