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The use of advanced biomaterials as a structural and functional support for stem cells-based therapeutic implants has boosted the development of tissue engineering applications in multiple clinical fields. In relation to neurological disorders, we are still far from the clinical reality of restoring normal brain function in neurodegenerative diseases and cerebrovascular disorders. Hydrogel polymers show unique mechanical stiffness properties in the range of living soft tissues such as nervous tissue. Furthermore, the use of these polymers drastically enhances the engraftment of stem cells as well as their capacity to produce and deliver neuroprotective and neuroregenerative factors in the host tissue. Along this article, we review past and current trends in experimental and translational research to understand the opportunities, benefits, and types of tentative hydrogel-based applications for the treatment of cerebral disorders. Although the use of hydrogels for brain disorders has been restricted to the experimental area, the current level of knowledge anticipates an intense development of this field to reach clinics in forthcoming years. [ABSTRACT FROM AUTHOR]

Ischemic stroke represents one of the most prevalent pathologies in humans and is a leading cause of death and disability. Anti-thrombolytic therapy with tissue plasminogen activator (t-PA) and surgical thrombectomy are the primary treatments to recanalize occluded vessels and normalize the blood flow in ischemic and peri-ischemic regions. A large majority of stroke patients are refractory to treatment or are not eligible due to the narrow time window of therapeutic efficacy. In recent decades, we have significantly increased our knowledge of the molecular and cellular mechanisms that inexorably lead to progressive damage in infarcted and peri-lesional brain areas. As a result, promising neuroprotective targets have been identified and exploited in several stroke models. However, these considerable advances have been unsuccessful in clinical contexts. This lack of clinical translatability and the emerging use of biomaterials in different biomedical disciplines have contributed to developing a new class of biomaterial-based systems for the better control of drug delivery in cerebral disorders. These systems are based on specific polymer formulations structured in nanoparticles and hydrogels that can be administered through different routes and, in general, bring the concentrations of drugs to therapeutic levels for prolonged times. In this review, we first provide the general context of the molecular and cellular mechanisms impaired by cerebral ischemia, highlighting the role of excitotoxicity, inflammation, oxidative stress, and depolarization waves as the main pathways and targets to promote neuroprotection avoiding neuronal dysfunction. In the second part, we discuss the versatile role played by distinct biomaterials and formats to support the sustained administration of particular compounds to neuroprotect the cerebral tissue at risk of damage. [ABSTRACT FROM AUTHOR]