Organoids as translational models in neuroregeneration after central nervous system injury

Central nervous system (CNS) injuries, including traumatic brain injury and spinal cord injury, affect millions of individuals worldwide annually, resulting in profound long-term disability and significant socioeconomic burden. Despite decades of research, effective neuroregenerative therapies remain elusive, largely due to inadequate preclinical models. Traditional two-dimensional cultures and animal models, while valuable, fail to capture the complexity of human neural tissue architecture and disease pathophysiology, thereby limiting translational success. This literature review examines neural organoids – three-dimensional, self-organizing tissue structures derived from human pluripotent stem cells – as transformative tools for bridging the translational gap in CNS injury research. We synthesize current knowledge on the biological principles governing organoid generation, including self-organization, extracellular matrix scaffolding, and bioreactor optimization. We evaluate diverse organoid types – cortical, cerebellar, spinal cord organoids, and brain assembloids – and their applications in modeling traumatic brain injury, ischemic stroke, and neurodegenerative pathologies. Additionally, we discuss organoid utility in preclinical drug screening and therapeutic development, including neuroprotective agents and gene therapies. Patient-derived organoids offer particular promise for personalized disease investigation and precision medicine. While organoids demonstrate superior predictive accuracy and human-relevant complexity compared to conventional models, significant ethical considerations regarding organoid consciousness, human-animal chimeras, donor autonomy, and commercialization warrant careful governance. This review demonstrates that neural organoids represent a revolutionary technology advancing translational neuroscience and regenerative medicine, while highlighting the critical importance of rigorous ethical oversight in their application.