Injectable micropore-forming microgel scaffold for neural progenitor cells transplantation and vascularization after stroke.

Abstract

Stem cell therapy for stroke is hindered by poor cell survival and integration within the ischemic microenvironment. Injectable microgels have been widely employed in cell delivery for their ability to promote cell infiltration, but dense hydrogel networks often limit cell survival. Here we present an injectable microgel-matrix composite scaffold that combines microporous microgels for neural progenitor cells (NPCs) delivery with interstitial spaces to support vascular growth. Using a gas-shearing fabrication approach, primary rat NPCs are efficiently encapsulated in phase-separated microporous microgel (PSMM), exhibiting superior survival and proliferation. In vitro studies demonstrate that PSMM scaffolds support endothelial cell (EC) sprouting and vascular formation, and in ischemic stroke rats, this formulation significantly enhance NPC loading capacity, survival, and differentiation, along with increased EC proliferation and infiltration. Ultimately, the microgel-matrix scaffold enhances long-term neurological recovery in stroke models, offering an efficient strategy that couples high cell loading with vascularization to advance regenerative medicine.