Bioinspired microvascular networks for stroke recovery, cerebral revascularization, and neuroprotection.

Cerebral ischemic stroke remains a leading cause of disability, with limited options for restoring cerebral blood flow (CBF) and promoting recovery. This study introduces a leaf-mimetic microvascular network to promote poststroke revascularization. The network uses leaf-venation-inspired microchannel templates to direct cell-hydrogel self-assembly into microvascular networks. In a photothrombotic stroke model, the implanted network integrates with host vessels, enhances neovascularization, improves CBF, reduces infarct volume, improves neuronal survival, and promotes functional recovery. Transcriptomic and histological analyses suggest enrichment of potentially reparative neutrophils and reduced inflammation associated with neutrophil extracellular traps as components of the network-associated immune-vascular response. Blocking neutrophil recruitment attenuates network-mediated neovascularization, whereas local delivery of potentially reparative neutrophils partially restores vascular remodeling. These findings provide a preclinical proof of concept that bioinspired microvascular constructs can promote cerebral revascularization and neuroprotection after stroke, while identifying immune-vascular processes that warrant further mechanistic and translational validation.