Growth factors can stimulate tissue regeneration, but the side effects and low effectiveness associated with suboptimal delivery systems have impeded their use in translational regenerative medicine. Physiologically, growth factor interactions with the extracellular matrix control their bioavailability and spatiotemporal cellular signalling. Growth factor signalling is also controlled at the cell surface level via binding to heparan sulfate proteoglycans, such as syndecans. Here we show that vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor-BB (PDGF-BB) that were engineered to have a syndecan-binding sequence trigger sustained low-intensity signalling (tonic signalling) and reduce the desensitization of growth factor receptors. We also show in mouse models that tonic signalling leads to superior morphogenetic activity, with syndecan-binding growth factors inducing greater bone regeneration and wound repair than wild-type growth factors, as well as reduced tumour growth (associated with PDGF-BB delivery) and vascular permeability (triggered by VEGF-A). Tonic signalling via syndecan binding may also enhance the regenerative capacity of other growth factors.

中文翻译：

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具有增强的syndecan结合力的生长因子产生滋补信号并促进组织愈合。

生长因子可以刺激组织再生，但是与次优递送系统相关的副作用和低效性阻碍了它们在转化再生医学中的应用。从生理上讲，生长因子与细胞外基质的相互作用控制着它们的生物利用度和时空细胞信号传导。生长因子信号转导也通过与硫酸乙酰肝素蛋白聚糖（如癸癸聚糖）结合而在细胞表面水平控制。在这里，我们表明，经工程改造以具有辛迪康结合序列的血管内皮生长因子-A（VEGF-A）和血小板衍生的生长因子-BB（PDGF-BB）触发了持续的低强度信号传导（张力信号）并降低了生长因子受体的脱敏。我们还在小鼠模型中显示，滋补信号传导导致优异的形态发生活性，与野生型生长因子相比，与多糖结合的生长因子诱导更大的骨再生和伤口修复，并降低了肿瘤的生长（与PDGF-BB递送相关）和血管通透性（由VEGF-A触发）。通过syndecan结合的强直信号也可以增强其他生长因子的再生能力。