机械转化
细胞生物学
血管生成
细胞外基质
骨愈合
伤口愈合
再生(生物学)
RGD基序
化学
解剖
材料科学
整合素
生物
免疫学
癌症研究
细胞
生物化学
作者
Julia Mehl,Saeed Khomeijani Farahani,Erik Brauer,Alexandra Klaus‐Bergmann,Tobias Thiele,Agnes Ellinghaus,Eireen Bartels‐Klein,Katharina Koch,Katharina Schmidt‐Bleek,Ansgar Petersen,Holger Gerhardt,Viola Vogel,Georg N. Duda
标识
DOI:10.1002/advs.202307050
摘要
Abstract Bone fracture healing is regulated by mechanobiological cues. Both, extracellular matrix (ECM) deposition and microvascular assembly determine the dynamics of the regenerative processes. Mechanical instability as by inter‐fragmentary shear or compression is known to influence early ECM formation and wound healing. However, it remains unclear how these external cues shape subsequent ECM and microvascular network assembly. As transcriptional coactivators, the mechanotransducers yes‐associated protein 1 (YAP)/transcriptional coactivator with PDZ‐binding motif (TAZ) translate physical cues into downstream signaling events, yet their role in sprouting angiogenesis into the hematoma after injury is unknown. Using bone healing as model system for scar‐free regeneration, the role of endothelial YAP/TAZ in combination with tuning the extrinsic mechanical stability via fracture fixation is investigated. Extrinsically imposed shear across the gap delayed hematoma remodeling and shaped the morphology of early collagen fiber orientations and microvascular networks, suggesting that enhanced shear increased the nutrient exchange in the hematoma. In contrast, endothelial YAP/TAZ deletion has little impact on the overall vascularization of the fracture gap, yet slightly increases the collagen fiber deposition under semi‐rigid fixation. Together, these data provide novel insights into the respective roles of endothelial YAP/TAZ and extrinsic mechanical cues in orchestrating the process of bone regeneration.
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