Translational Considerations for Injectable Biomaterials and Bioscaffolds to Repair and Regenerate Brain Tissue

Adult neurogenesis can replace lost neurons through migration and participate in the repair of damaged tissues. Neurogenesis by itself is known to be insufficient to replace lost tissue. Injectable bioscaffolds derived from extracellular matrix (ECM) have shown promise in repairing and regenerating brain tissue. These bioscaffolds need to be considered within their pathological context (e.g. proteases), which contribute to its biodegradation. Biodegradation through peripheral immune cells is required to promote the invasion of brain cells and reconstitute a de novo tissue. In addition to the biomaterial characteristics, a greater focus on translational considerations (e.g., intracerebral delivery) is required to establish a robust pathway to the clinic. Especially advances in developing large animal models will be required to address key issues, such as regrowing of a gyrencephalic brain, as well as potential limitations to tissue regeneration due to the size of the volumetric deficits. It is advocated that non-human primates will be an essential step prior to first-in-human investigations. Injectable bioscaffolds have the potential to promote a paradigm shift in the treatment of acute brain injuries, but this can only be achieved through a robust and potentially iterative translational effort.