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In the central nervous system (CNS), a self\u2010reinforcing cascade of neuroinflammation, oxidative stress, blood\u2010brain barrier breakdown, and glial fibrotic scarring restricts long\u2010distance axonal regrowth and graft survival. The peripheral nervous system (PNS) exhibits greater intrinsic regenerative potential, yet critical\u2010length defects remain challenging and have driven the development of clinically relevant conduit designs. This review provides an overview of the microenvironment following CNS injury and summarizes the key design requirements for engineered repair matrices, while highlighting lessons from advanced peripheral nerve guidance conduits. Injectable extracellular matrix (ECM)\u2010mimetic and smart hydrogels can conformally fill CNS cavities, modulate immune and redox cascades, restore vascular function, and provide permissive niches for neural stem\/progenitor and endothelial cells. CNS\u2010compatible bioinks and 3D bioprinting enable the fabrication of neurovascular architectures and multicellular constructs with controlled mechanics, topology, and circuit geometry. Advances in nerve guidance conduits inform translation of PNS principles to the brain and spinal cord. Organoid\u2010based strategies, including vascularized organoids, biomaterial\u2010supported grafts, and organoid\u2010neuroelectronic interfaces, suggest routes toward modular biohybrid constructs. Integrating pathology\u2010informed biomaterials, biofabrication, and organoid engineering offers a roadmap for neural circuit reconstruction.<\/jats:p>","DOI":"10.1002\/adhm.71115","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T07:27:52Z","timestamp":1775114872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rethinking Neuroregenerative Microenvironments: Synergy Between Bioengineering and Organoids"],"prefix":"10.1002","volume":"15","author":[{"given":"He","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Neurology Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Robotics Shenyang Institute of Automation Chinese Academy of Sciences  Shenyang Liaoning 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