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Delivery of a pro\u2010angiogenic stimulus via acellular materials offers several benefits over biological therapies but has been hampered by interaction of the implanted material with the innate immune response. However, macrophages, a key component of the innate immune response, release a plurality of soluble factors that can be harnessed to stimulate neovascularization and restore blood flow to damaged tissue. This study investigates the ability of biodegradable poly(D,L\u2010lactic\u2010co\u2010glycolic acid) (PLGA) microspheres to restore tissue perfusion in a hind limb model of ischaemia. Microspheres exhibiting a hierarchical porous structure are associated with an increase in blood flow at day 21 post\u2010implantation compared with solid microspheres composed of the same polymer. This corresponds with an increase in blood vessel density in the surrounding tissue. In vitro simulation of the foreign body response observed demonstrates M2\u2010like macrophages incubated with the porous microspheres secreted increased amounts of vascular endothelial growth factor (VEGF) compared with M1\u2010like macrophages providing a potential mechanism for the increased neovascularization. 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