Biphasic oxygen-regulating cyanobacterial hydrogel for synergistic ischemic stroke gas therapy and post-stroke...

Ischemic stroke (87% of stroke cases) results from cerebral artery occlusion. Reperfusion therapy restores cerebral blood flow but predisposes to dual complications: ischemia-reperfusion injury (IRI) caused by oxygen fluctuations exacerbating neural damage and post-stroke depression (PSD). This study develops a cyanobacteria hydrogel composite (PT-CUCBD) for comprehensive reperfusion protection through precisely regulating the oxygen (O₂) microenvironment during distinct reperfusion phases. During pre-reperfusion phase, upconversion nanoparticles emit 660/450 nm light under 808 nm near-infrared irradiation for photosynthetic O₂ production, thereby alleviating pre-reperfusion hypoxia, while ultraviolet light triggers nitric oxide (NO) release to promote angiogenesis. More importantly, during post-reperfusion phase, cessation of irradiation activates cyanobacterial respiration to deplete excess O₂, mitigating reoxygenation injury. Simultaneously, PT-CUCBD efficiently scavenges reactive oxygen species (ROS), while its loaded diallyl trisulfide releases hydrogen sulfide (H₂S) in response to glutathione to enhance neuroprotection. Furthermore, it promotes macrophage polarization toward the anti-inflammatory M2-type, suppressing neuroinflammation and apoptosis. Notably, experimental results demonstrate that, this multifunctional platform not only prevents IRI, but also significantly reduces the risk of PSD, establishing a promising therapeutic paradigm for ischemic stroke.