Due to increasing life expectancy incidence of neurological disorders is rapidly rising, thus adding urgencyto develop effective strategies for treatment. Stem cell-based therapies were considered highly promisingand while progress in this field is evident, outcomes of clinical trials are rather disappointing. Suboptimalengraftment, poor cell survival and uncontrolled differentiation may be the reasons behind dismal results.Clearly, new direction is needed and we postulate that with recent progress in biomaterials and bioprint-ing, regenerative approaches for neurological applications may be finally successful. The use of biomate-rials aids engraftment of stem cells, protects them from harmful microenvironment and importantly, itfacilitates the incorporation of cell-supporting molecules. The biomaterials used in bioprinting (thebioinks) form a scaffold for embedding the cells/biomolecules of interest, but also could be exploited asa source of endogenous contrast or supplemented with contrast agents for imaging. Additionally, bioprint-ing enables patient-specific customization with shape/size tailored for actual needs. In stroke or traumaticbrain injury for example lesions are localized and focal, and usually progress with significant loss of tissuevolume creating space that could be filled with artificial tissue using bioprinting modalities. The value ofimaging for bioprinting technology is advantageous on many levels including design of custom shapesscaffolds based on anatomical 3D scans, assessment of performance and integration after scaffold implan-tation, or to learn about the degradation over time. In this review, we focus on bioprinting technologydescribing different printing techniques and properties of biomaterials in the context of requirementsfor neurological applications. We also discuss the need forin vivoimaging of implanted materials and tis-sue constructs reviewing applicable imaging modalities and type of information they can provide.

Cell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in extensive or global diseases such as stroke or amyotrophic lateral sclerosis (ALS). However, the precision and efficacy of this approach are still a challenge. Hydrogels were introduced to minimize cell sedimentation and improve cell viability. At the same time, contrast agents were integrated to allow image-guided injection. Here, we report using manganese ions (Mn<sup>2+</sup>) as a dual agent for cross-linking alginate-based hydrogels and magnetic resonance imaging (MRI). We performed in vitro studies to test the Mn<sup>2+</sup> alginate hydrogel formulations for biocompatibility, injectability, MRI signal retention time, and effect on cell viability. The selected formulation was injected intrathecally into pigs under MRI control. The biocompatibility test showed a lack of immune response, and cells suspended in the hydrogel showed greater viability than monolayer culture. Moreover, Mn<sup>2+</sup>-labeled hydrogel produced a strong T1 MRI signal, which enabled MRI-guided procedure. We confirmed the utility of Mn<sup>2+</sup> alginate hydrogel as a carrier for cells in large animals and a contrast agent at the same time.

This work aims to engineer a new stable injectable Mn-based methacrylated gellan gum (Mn/GG-MA) hydrogel for real-time monitored cell delivery into the central nervous system. To enable the hydrogel visualization under Magnetic Resonance Imaging (MRI), GG-MA solutions were supplemented with paramagnetic Mn2+ ions before its ionic crosslink with artificial cerebrospinal fluid (aCSF). The resulting formulations were stable, detectable by T1-weighted MRI scans and also injectable. Cell-laden hydrogels were prepared using the Mn/GG-MA formulations, extruded into aCSF for crosslink, and after 7 days of culture, the encapsulated human adipose-derived stem cells remained viable, as assessed by Live/Dead assay. In vivo tests, using double mutant MBPshi/shi/rag2 immunocompromised mice, showed that the injection of Mn/GG-MA solutions resulted in a continuous and traceable hydrogel, visible on MRI scans. Summing up, the developed formulations are suitable for both non-invasive cell delivery techniques and image-guided neurointerventions, paving the way for new therapeutic procedures.