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

力学边界条件作为骨再生和适应的驱动因素的相关性被广泛接受。此外，骨折区的功能性血管生成和血管供应也被认为是愈合和再生组织活力的关键因素。然而，组织力学条件和血管生成之间的关系和相互依赖性还没有得到很好的理解。最近的工作表明，在早期愈伤组织形成和内皮细胞-细胞相互作用中，外在力学对成纤维细胞网络的自组织起着关键作用，作为对血流驱动血管网络形成的反应。周细胞和血管平滑肌细胞赋予新生血管稳定性和直径控制。但是成纤维细胞和/或周细胞如何从周围的愈伤组织传递机械输入以适应血管模式还没有研究。我们的主要目标是了解在骨愈合过程中，机械负荷如何影响年轻人和老年人的功能性血管网形成和早期骨痂组织。这项工作将有助于解开外部施加的负载，成纤维细胞自组织，周细胞反应，血管网络形成，以及损伤后早期软骨痂和骨髓重组之间的年龄依赖性信号通路。

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.