Bioengineering Microporous Annealed Particle Scaffolds to Recruit Neural Progenitor Stem Cells and Promote Angiogenesis in the Stroke Core

Abstract

There remains a significant gap in the need for regenerative therapies for stroke compared to what is currently available. An ideal therapy would be one that stimulates the formation of new tissue with the ability to regain any function previously lost due to stroke. Therefore, methods exploiting the plasticity of the brain and modulating endogenous cellular responses to promote repair in the stroke core after ischemia have become highly attractive. However, this process of neural regeneration is complex and requires a series of controlled biological events, such as recruitment and differentiation of neuron progenitor cells (NPC’s), angiogenesis, and axonogenesis. Biomaterials are now commonly used to research tissue regeneration and cellular mechanisms, both in vitro and in vivo. We have designed a biocompatible biomaterial from macroporous annealed particles (MAP) hydrogels for injection into the stroke core five days after a photothrombotic stroke. Our hyaluronic acid-based material has been modified to dictate NPC fate in vitro through maintained stemness and the formation of neurospheres or towards Tuj1 positive NPCs, as well as enhance angiogenesis and the recruitment of endogenous NPCs after stroke. We have observed the first case of significant angiogenesis throughout the entire stroke core within only 10 days after injection, or 15 days post stroke. As well as significant increase in Tuj1+ and Nestin+ cells.