External mechanical loading overrules cell-cell mechanical communication in sprouting angiogenesis during early bone...

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Mechanobiology

Background:

• Sprouting angiogenesis is crucial for bone regeneration, but delayed healing can occur with insufficient revascularization.
• Endothelial cells are mechano-sensitive, responding to both cell-induced traction forces and external physiological loads during healing.
• The distinct roles of these mechanical cues in early bone healing angiogenesis and sprout patterning are not well understood.

Purpose of the Study:

• To investigate the relative importance of externally applied and cell-induced mechanical signals in driving sprout patterning during early bone healing.
• To model cellular self-organization in early bone healing, considering mechano-regulation of angiogenesis and stromal cell organization.

Main Methods:

• Development of an in silico computational model for mechano-regulated sprouting angiogenesis and stromal cell organization.
• Comparison of model predictions with in vivo experiments using a mouse osteotomy model with rigid and semi-rigid fixation.

Main Results:

• The magnitude and orientation of principal strains in the healing region accurately predicted observed sprout patterning under both fixation conditions.
• Simulations showed that external mechanical signals dominate over cell-cell mechanical communication when either cue is selectively inhibited.

Conclusions:

• External mechanical signals play a more significant role in directing sprout patterning than local cell-mediated mechanical cues during early bone healing.
• These findings highlight the importance of mechanical environment in fracture treatment strategies to optimize bone regeneration.