Notwithstanding the remarkable progress in vascular network engineering, implanted bioengineered microvessels mostly fail to form anastomoses with the host vasculature. Here we demonstrate that implants containing assembled human vascular networks (A-grafts) fail to engraft owing to their inability to engage non-inflammatory host neutrophils upon implantation into mice. By contrast, unassembled vascular cells (U-grafts) readily engage alternatively polarized neutrophils, which in turn serve as indispensable mediators of vascular assembly and anastomosis. The depletion of host neutrophils abrogated vascularization in U-grafts, whereas an adoptive transfer of neutrophils fully restored vascularization in myeloid-depleted mice. Neutrophil engagement was regulated by secreted factors and was progressively silenced as the vasculature matured. Exogenous addition of factors from U-grafts re-engaged neutrophils and enhanced revascularization in A-grafts, a process that was recapitulated by blocking Notch signalling. Our data suggest that the pro-vascularization potential of neutrophils can be harnessed to improve the engraftment of bioengineered tissues.

尽管在血管网络工程方面取得了显着进展，但植入的生物工程微血管在大多数情况下仍无法与宿主脉管系统形成吻合。在这里，我们证明了包含组装的人类血管网络（A移植物）的植入物由于无法在植入小鼠中时与非炎症宿主嗜中性白细胞接合而无法植入。相比之下，未组装的血管细胞（U型移植物）很容易与极化的嗜中性粒细胞结合，进而成为血管组装和吻合的必不可少的介质。宿主中性粒细胞的耗竭消除了U型移植物中的血管形成，而嗜中性粒细胞的过继转移完全恢复了骨髓缺乏小鼠的血管形成。中性粒细胞的参与受分泌因子的调节，并随着脉管系统的成熟而逐渐沉默。从U移植物中外源添加因子会重新参与嗜中性粒细胞并增强A移植物中的血运重建，这一过程通过阻断Notch信号得以概括。我们的数据表明，可以利用中性粒细胞的促血管形成潜力来改善生物工程组织的植入。