Advances in bioinks and in vivo imaging of biomaterials for CNS applications

Due to increasing life expectancy incidence of neurological disorders is rapidly rising, thus adding urgency to develop effective strategies for treatment. Stem cell-based therapies were considered highly promising and while progress in this field is evident, outcomes of clinical trials are rather disappointing. Suboptimal engraftment, 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 bioprinting, regenerative approaches for neurological applications may be finally successful. The use of biomaterials aids engraftment of stem cells, protects them from harmful microenvironment and importantly, it facilitates the incorporation of cell-supporting molecules. The biomaterials used in bioprinting (the bioinks) form a scaffold for embedding the cells/biomolecules of interest, but also could be exploited as a source of endogenous contrast or supplemented with contrast agents for imaging. Additionally, bioprinting enables patient-specific customization with shape/size tailored for actual needs. In stroke or traumatic brain injury for example lesions are localized and focal, and usually progress with significant loss of tissue volume creating space that could be filled with artificial tissue using bioprinting modalities. The value of imaging for bioprinting technology is advantageous on many levels including design of custom shapes scaffolds based on anatomical 3D scans, assessment of performance and integration after scaffold implantation, or to learn about the degradation over time. In this review, we focus on bioprinting technology describing different printing techniques and properties of biomaterials in the context of requirements for neurological applications. We also discuss the need for in vivo imaging of implanted materials and tissue constructs reviewing applicable imaging modalities and type of information they can provide. Statement of Significance: Current stem cell-based regenerative strategies for neurological diseases are ineffective due to inaccurate engraftment, low cell viability and suboptimal differentiation. Bioprinting and embedding stem cells within biomaterials at high precision, including building complex multi-material and multi-cell type composites may bring a breakthrough in this field. We provide here comprehensive review of bioinks, bioprinting techniques applicable to application for neurological disorders. Appreciating importance of longitudinal monitoring of implanted scaffolds, we discuss advantages of various imaging modalities available and suitable for imaging biomaterials in the central nervous system. Our goal is to inspire new experimental approaches combining imaging, biomaterials/bioinks, advanced manufacturing and tissue engineering approaches, and stimulate interest in image-guided therapies based on bioprinting.