Establishing vascular neural networks is critical for tissue regeneration. However, none of the existing approaches can replicate the physiological processes that varying extracellular cues sequentially play parts in different phases, thus hindering synergistic neurovascular remodeling. Here, we report a ferroelectric living interface for fine-tuned exosome secretion (LIFES) that harnesses unique topographical and electric (piezoelectric and photopyroelectric) signals and sustained generation of bioactive exosomes by rationally constructing a ferroelectric layer and a living cell layer. The LIFES exhibits physiology-mimicking paracrine effects, including sustained (∼192 h), phase-specific exosome secretion with tunable contents (∼8-fold increases) and programmable microRNA (miRNA) cargoes (initially pro-angiogenic and later pro-neurogenic), which overcome the limitations of the existing exosome delivery systems, such as short lifetime (∼24–48 h), difficult-to-preserve bioactivity, and non-changeable cargoes. LIFES allows for enhanced effectiveness in promoting neurovascular remodeling both in vitro and in challenging diabetic wound models, opening new avenues for next-generation intelligent materials and biomedical devices.

中文翻译：

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一种铁电生活界面，用于微调外泌体分泌，以实现生理模拟神经血管重塑


建立血管神经网络对于组织再生至关重要。然而，现有的方法都无法复制不同的细胞外线索在不同阶段依次发挥作用的生理过程，从而阻碍了协同神经血管重塑。在这里，我们报道了一种用于微调外泌体分泌 （LIFES） 的铁电生活界面，它利用独特的地形和电（压电和光热释电）信号，并通过合理构建铁电层和活细胞层来持续产生生物活性外泌体。LIFES 表现出模拟生理学的旁分泌效应，包括持续 （∼192 h）、具有可调内容物的阶段特异性外泌体分泌（∼8 倍增加）和可编程的 microRNA （miRNA） 货物（最初是促血管生成，后来是促神经原性的），克服了现有外泌体递送系统的局限性，例如寿命短 （∼24-48 h）、难以保存的生物活性和不可更换的货物。LIFES 可以提高体外和具有挑战性的糖尿病伤口模型促进神经血管重塑 的有效性，为下一代智能材料和生物医学设备开辟新途径。