Tissue Engineering and Biomaterial Strategies to Elicit Endogenous Neuronal Replacement in the Brain

Abstract

Neurogenesis in the postnatal mammalian brain is known to occur in the dentate gyrus of the hippocampus and the subventricular zone. These neurogenic niches serve as endogenous sources of neural precursor cells that could potentially replace neurons that have been lost or damaged throughout the brain. As an example, manipulation of the subventricular zone to augment neurogenesis has become a popular strategy for attempting to replace neurons that have been lost due to acute brain injury or neurodegenerative disease. In this review article, we describe current experimental strategies to enhance the regenerative potential of endogenous neural precursor cell sources by enhancing cell proliferation in neurogenic regions and/or redirecting migration, including pharmacological, biomaterial, and tissue engineering strategies. In particular, we discuss a novel replacement strategy based on exogenously biofabricated "living scaffolds" that could enhance and redirect endogenous neuroblast migration from the subventricular zone to specified regions throughout the brain. This approach utilizes the first implantable, biomimetic tissue-engineered rostral migratory stream, thereby leveraging the brain's natural mechanism for sustained neuronal replacement by replicating the structure and function of the native rostral migratory stream. Across all these strategies, we discuss several challenges that need to be overcome to successfully harness endogenous neural precursor cells to promote nervous system repair and functional restoration. With further development, the diverse and innovative tissue engineering and biomaterial strategies explored in this review have the potential to facilitate functional neuronal replacement to mitigate neurological and psychiatric symptoms caused by injury, developmental disorders, or neurodegenerative disease.

Biosensing surfaces and therapeutic biomaterials for the central nervous system in COVID-19

“…Changes in the composition of the brain ECM have an important role in neuropathologies [ 104 ]. Tissue engineering and biomaterials attempt for the ECM to be in equilibrium [ 105 ].…”

Assessing the Feasibility of Developing in vivo Neuroprobes for Parallel Intracellular Recording and Stimulation: A Perspective

“…These niches serve as endogenous sources of neural precursor cells that can migrate and thus may potentially replace damaged or lost neurons at the site of injury. Attempts to develop neuro-engineering approaches to facilitate the migration of neuro-precursor cells toward “remote” sites of injury are underway ( Bressan and Saghatelyan, 2020 ; Purvis et al, 2020 ). It is conceivable for the time being that implantation of 3D vertical nanopillar-based probes close to or at the sources of endogenous precursor neurons will reveal accelerated probability for a direct neuron/electrode interfaces.…”

Unique Astrocyte Cytoskeletal and Nuclear Morphology in a Three-Dimensional Tissue-Engineered Rostral Migratory Stream

“…Neuroglia 2022, 3 42 A variety of biomaterial and tissue engineering strategies have been developed to enhance the redirection of SVZ neuroblasts throughout the brain following neuronal injury [23][24][25]. These strategies have increased the quantity of neuroblasts entering injured brain regions by augmenting chemoattractant cues and/or by providing a physical substrate for migration [23].…”

“…Neuroglia 2022, 3 42 A variety of biomaterial and tissue engineering strategies have been developed to enhance the redirection of SVZ neuroblasts throughout the brain following neuronal injury [23][24][25]. These strategies have increased the quantity of neuroblasts entering injured brain regions by augmenting chemoattractant cues and/or by providing a physical substrate for migration [23]. Drawing inspiration from the SVZ-RMS-OB pathway, our laboratory has developed a biologically relevant, implantable "living scaffold" that emulates the glial tube of the endogenous RMS [26][27][28][29].…”